Pub Date : 2024-09-03DOI: 10.1186/s13063-024-08436-8
R S Joosen, M Voskuil, T B Krasemann, N A Blom, G J Krings, J M P J Breur
Background: Branch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions.
Methods: This is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2-4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL.
Discussion: This trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions.
Trial registration: ClinicalTrials.gov NCT05809310. Registered on March 15, 2023.
背景:肺动脉分支(PA)狭窄是大动脉转位(TGA)、法洛氏四联症(ToF)和动脉导管未闭(TA)患者经皮介入治疗的最常见适应症之一。然而,经皮分支 PA 干预术对运动能力的影响在很大程度上仍是未知数。此外,根据国际指南,对于无症状患者进行介入治疗的最佳时机还没有达成共识。本试验旨在确定经皮介入治疗 PA 支路狭窄对 TGA、ToF 和 TA 患者运动能力的影响。此外,它还旨在评估对 RV 功能的影响,并确定 RV 适应性和 RV 功能障碍的早期标志物,以改善这些干预措施的时机:这是一项随机多中心干预试验。根据国际指南,TGA、ToF 和 TA 患者年龄≥ 8 岁,具有经皮分支 PA 干预的 IIa 级指征,均有资格参与。患者将被随机分为介入组和对照组(保守治疗 6 个月)。所有患者将在基线、6 个月和 2-4 年的随访期间接受经胸超声心动图、心脏磁共振成像和心肺运动测试。生活质量(QoL)问卷调查将在基线、干预后 2 周或对照组类似范围以及随访 6 个月时进行。主要结果是以最大摄氧量(峰值 VO2 占预测值的百分比)表示的运动能力。干预组与对照组相比,最大摄氧量(峰值 VO2 占预测值的百分比)增加 14%(功率 80%,总体 1 类误差控制在 5%),需要 56 名患者(干预组 n = 28,对照组 n = 28)的参与。次要结果包括 RV 收缩功能、RV 功能、RV 重塑、手术成功率、并发症、肺灌注和 QoL 的各种参数:该试验将研究经皮分支PA干预对TGA、ToF和TA患者运动能力的影响,并将确定RV适应和RV功能障碍的早期标志物,以改善干预时机:试验注册:ClinicalTrials.gov NCT05809310。注册日期:2023 年 3 月 15 日。
{"title":"The effects of percutaneous branch pulmonary artery interventions in biventricular congenital heart disease: study protocol for a randomized controlled Dutch multicenter interventional trial.","authors":"R S Joosen, M Voskuil, T B Krasemann, N A Blom, G J Krings, J M P J Breur","doi":"10.1186/s13063-024-08436-8","DOIUrl":"10.1186/s13063-024-08436-8","url":null,"abstract":"<p><strong>Background: </strong>Branch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions.</p><p><strong>Methods: </strong>This is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2-4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO<sub>2</sub> as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO<sub>2</sub> as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL.</p><p><strong>Discussion: </strong>This trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05809310. Registered on March 15, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited.
Methodology: This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks.
Outcome measures: International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity.
Discussion: The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia.
Trial registration: Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.
{"title":"Effect of aerobic exercise program on neuropathic pain and quality of life in person with paraplegia: study protocol for a randomized controlled trial.","authors":"Ankush Gera, Shefali Walia, Stuti Khanna, Garima Wadhwa","doi":"10.1186/s13063-024-08430-0","DOIUrl":"10.1186/s13063-024-08430-0","url":null,"abstract":"<p><strong>Background: </strong>Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited.</p><p><strong>Methodology: </strong>This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks.</p><p><strong>Outcome measures: </strong>International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity.</p><p><strong>Discussion: </strong>The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia.</p><p><strong>Trial registration: </strong>Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s13063-024-08410-4
Elias T Sawaya, Benjamin Sommier, Jean-Maxime Alet, Pierre-Thierry Piechaud, Flore-Anne Lecoq
Background: Dupuytren's contracture is a hereditary disorder which causes progressive fibrosis of the palmar aponeurosis of the hand, resulting in digital flexion contractures of the affected rays. Limited fasciectomy is a standard surgical treatment for Dupuytren's, and the one with the lowest recurrence rate; however, the recurrence is still relatively high (2-39%). Adipose-derived stem cells have been shown to inhibit Dupuytren's myofibroblasts proliferation and contractility in vitro, as well as to improve scar quality and skin regeneration in different types of surgeries. Autologous adipose tissue grafting has already been investigated as an adjuvant treatment to percutaneous needle fasciotomy for Dupuytren's contracture with good results, but it was only recently associated with limited fasciectomy. The purpose of REMEDY trial is to investigate if limited fasciectomy with autologous adipose tissue grafting would decrease recurrence compared to limited fasciectomy alone.
Methods: The REMEDY trial is a multi-centre open-label randomised controlled trial (RCT) with 1:1 allocation ratio. Participants (n = 150) will be randomised into two groups, limited fasciectomy with autologous adipose tissue grafting versus limited fasciectomy alone. The primary outcome is the recurrence of Dupuytren's contracture on any of the treated rays at 2 years postoperatively. The secondary outcomes are recurrence at 3 and 5 years, scar quality, complications, occurrence of algodystrophy (complex regional pain syndrome), patient-reported hand function, and hypodermal adipose tissue loss at 1 year postoperatively in a small subset of patients.
Discussion: The REMEDY trial is one of the first studies investigating limited fasciectomy associated with autologous adipose tissue grafting for Dupuytren's contracture, and, to our knowledge, the first one investigating long-term outcomes of this treatment. It will provide insight into possible benefits of combining adipose tissue grafting with limited fasciectomy, such as lower recurrence rate and improvement of scar quality.
Trial registration: ClinicalTrials.gov NCT05067764, June 13, 2022.
{"title":"Limited fasciectomy with versus without autologous adipose tissue grafting for treatment of Dupuytren's contracture (REMEDY): study protocol for a multicentre randomised controlled trial.","authors":"Elias T Sawaya, Benjamin Sommier, Jean-Maxime Alet, Pierre-Thierry Piechaud, Flore-Anne Lecoq","doi":"10.1186/s13063-024-08410-4","DOIUrl":"10.1186/s13063-024-08410-4","url":null,"abstract":"<p><strong>Background: </strong>Dupuytren's contracture is a hereditary disorder which causes progressive fibrosis of the palmar aponeurosis of the hand, resulting in digital flexion contractures of the affected rays. Limited fasciectomy is a standard surgical treatment for Dupuytren's, and the one with the lowest recurrence rate; however, the recurrence is still relatively high (2-39%). Adipose-derived stem cells have been shown to inhibit Dupuytren's myofibroblasts proliferation and contractility in vitro, as well as to improve scar quality and skin regeneration in different types of surgeries. Autologous adipose tissue grafting has already been investigated as an adjuvant treatment to percutaneous needle fasciotomy for Dupuytren's contracture with good results, but it was only recently associated with limited fasciectomy. The purpose of REMEDY trial is to investigate if limited fasciectomy with autologous adipose tissue grafting would decrease recurrence compared to limited fasciectomy alone.</p><p><strong>Methods: </strong>The REMEDY trial is a multi-centre open-label randomised controlled trial (RCT) with 1:1 allocation ratio. Participants (n = 150) will be randomised into two groups, limited fasciectomy with autologous adipose tissue grafting versus limited fasciectomy alone. The primary outcome is the recurrence of Dupuytren's contracture on any of the treated rays at 2 years postoperatively. The secondary outcomes are recurrence at 3 and 5 years, scar quality, complications, occurrence of algodystrophy (complex regional pain syndrome), patient-reported hand function, and hypodermal adipose tissue loss at 1 year postoperatively in a small subset of patients.</p><p><strong>Discussion: </strong>The REMEDY trial is one of the first studies investigating limited fasciectomy associated with autologous adipose tissue grafting for Dupuytren's contracture, and, to our knowledge, the first one investigating long-term outcomes of this treatment. It will provide insight into possible benefits of combining adipose tissue grafting with limited fasciectomy, such as lower recurrence rate and improvement of scar quality.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05067764, June 13, 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s13063-024-08419-9
Andrew Ayi-Ashong Bruce, Ama-Onyebuchi Umesi, Adedapo Bashorun, Magnus Ochoge, Mohammed Yisa, Dolapo Obayemi-Ajiboye, Ahmed Futa, Anna Njie, Selasi Asase, Modou Bella Jallow, Larry Kotei, Lucy Affleck, Olubunmi Abiola Olubiyi, Lamin B Jarju, Madi Kanyi, Baba Danso, Armel Zemsi, Ed Clarke
Background: Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed.
Methods: As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings.
Outcome: Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities.
Conclusion: Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings.
{"title":"Collecting and reporting adverse events in low-income settings-perspectives from vaccine trials in the Gambia.","authors":"Andrew Ayi-Ashong Bruce, Ama-Onyebuchi Umesi, Adedapo Bashorun, Magnus Ochoge, Mohammed Yisa, Dolapo Obayemi-Ajiboye, Ahmed Futa, Anna Njie, Selasi Asase, Modou Bella Jallow, Larry Kotei, Lucy Affleck, Olubunmi Abiola Olubiyi, Lamin B Jarju, Madi Kanyi, Baba Danso, Armel Zemsi, Ed Clarke","doi":"10.1186/s13063-024-08419-9","DOIUrl":"10.1186/s13063-024-08419-9","url":null,"abstract":"<p><strong>Background: </strong>Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed.</p><p><strong>Methods: </strong>As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings.</p><p><strong>Outcome: </strong>Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities.</p><p><strong>Conclusion: </strong>Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s13063-024-08414-0
Qian Liu, Huimei Zhou, Mei Yu, Dongyan Cao, Jiaxin Yang
Background: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.
Methods: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.
Ethics and dissemination: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.
Conclusions: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.
Trial registration number: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.
{"title":"GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol.","authors":"Qian Liu, Huimei Zhou, Mei Yu, Dongyan Cao, Jiaxin Yang","doi":"10.1186/s13063-024-08414-0","DOIUrl":"10.1186/s13063-024-08414-0","url":null,"abstract":"<p><strong>Background: </strong>Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.</p><p><strong>Methods: </strong>This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.</p><p><strong>Ethics and dissemination: </strong>The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.</p><p><strong>Conclusions: </strong>Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.</p><p><strong>Trial registration number: </strong>Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s13063-024-08424-y
Angela MacIsaac, Vamika Mann, Elaine Toombs, Fred Schmidt, Janine V Olthuis, Sherry H Stewart, Amanda Newton, Arto Ohinmaa, Aislin R Mushquash
Background: Technology use may be one strategy to promote mental health and wellbeing among young adults in post-secondary education settings experiencing increasing distress and mental health difficulties. The JoyPop™ app is mobile mental health tool with a growing evidence base. The objectives of this research are to (1) evaluate the effectiveness of the JoyPop™ app in improving emotion regulation skills (primary outcome), as well as mental health, wellbeing, and resilience (secondary outcomes); (2) evaluate sustained app use once users are no longer reminded and determine whether sustained use is associated with maintained improvements in primary and secondary outcomes; (3) determine whether those in the intervention condition have lower mental health service usage and associated costs compared to those in the control condition; and (4) assess users' perspectives on the quality of the JoyPop™ app.
Methods: A pragmatic, parallel arm randomized controlled trial will be used. Participants will be randomly allocated using stratified block randomization in a 1:1 ratio to the intervention (JoyPop™) or control (no intervention) condition. Participants allocated to the intervention condition will be asked to use the JoyPop™ app at least twice daily for 4 weeks. Participants will complete outcome measures at four assessment time-points (first [baseline], second [after 2 weeks], third [after 4 weeks], fourth [after 8 weeks; follow-up]). Participants in the control condition will be offered access to the app after the fourth assessment time-point.
Discussion: Results will determine the effectiveness of the JoyPop™ app for promoting mental health and wellbeing among post-secondary students. If effective, this may encourage more widespread adoption of the JoyPop™ app by post-secondary institutions as part of their response to student mental health needs.
Trial registration: ClinicalTrials.gov NCT06154369 . Registered on November 23, 2023.
{"title":"Promoting mental health and wellbeing among post-secondary students with the JoyPop™ app: study protocol for a randomized controlled trial.","authors":"Angela MacIsaac, Vamika Mann, Elaine Toombs, Fred Schmidt, Janine V Olthuis, Sherry H Stewart, Amanda Newton, Arto Ohinmaa, Aislin R Mushquash","doi":"10.1186/s13063-024-08424-y","DOIUrl":"10.1186/s13063-024-08424-y","url":null,"abstract":"<p><strong>Background: </strong>Technology use may be one strategy to promote mental health and wellbeing among young adults in post-secondary education settings experiencing increasing distress and mental health difficulties. The JoyPop™ app is mobile mental health tool with a growing evidence base. The objectives of this research are to (1) evaluate the effectiveness of the JoyPop™ app in improving emotion regulation skills (primary outcome), as well as mental health, wellbeing, and resilience (secondary outcomes); (2) evaluate sustained app use once users are no longer reminded and determine whether sustained use is associated with maintained improvements in primary and secondary outcomes; (3) determine whether those in the intervention condition have lower mental health service usage and associated costs compared to those in the control condition; and (4) assess users' perspectives on the quality of the JoyPop™ app.</p><p><strong>Methods: </strong>A pragmatic, parallel arm randomized controlled trial will be used. Participants will be randomly allocated using stratified block randomization in a 1:1 ratio to the intervention (JoyPop™) or control (no intervention) condition. Participants allocated to the intervention condition will be asked to use the JoyPop™ app at least twice daily for 4 weeks. Participants will complete outcome measures at four assessment time-points (first [baseline], second [after 2 weeks], third [after 4 weeks], fourth [after 8 weeks; follow-up]). Participants in the control condition will be offered access to the app after the fourth assessment time-point.</p><p><strong>Discussion: </strong>Results will determine the effectiveness of the JoyPop™ app for promoting mental health and wellbeing among post-secondary students. If effective, this may encourage more widespread adoption of the JoyPop™ app by post-secondary institutions as part of their response to student mental health needs.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT06154369 . Registered on November 23, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s13063-024-08409-x
Anna Kristensen-Alvarez, Mikkel Fode, Hein Vincent Stroomberg, Kurt Krøyer Nielsen, Albert Arch, Lars Birger Lönn, Mikkel Taudorf, Steven John Widecrantz, Andreas Røder
Background: One-fourth of men older than 70 years have lower urinary tract symptoms (LUTS) that impair their quality of life. Transurethral resection of the prostate (TURP) is considered the gold standard for surgical treatment of LUTS caused by benign prostatic hyperplasia (BPH) that cannot be managed conservatively or pharmacologically. However, TURP is only an option for patients fit for surgery and can result in complications. Transurethral microwave thermotherapy (TUMT) and prostatic artery embolisation (PAE) are alternative minimally invasive surgical therapies (MISTs) performed in an outpatient setting. Both treatments have shown to reduce LUTS with a similar post-procedure outcome in mean International Prostate Symptom Score (IPSS). It is however still unknown if TUMT and PAE perform equally well as they have never been directly compared in a randomised clinical trial. The objective of this clinical trial is to assess if PAE is non-inferior to TUMT in reducing LUTS secondary to BPH.
Methods: This study is designed as a multicentre, non-inferiority, open-label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments. The primary outcome is the IPSS of the two arms after 6 months. The primary outcome will be evaluated using a 95% confidence interval against the predefined non-inferiority margin of + 3 points in IPSS. Secondary objectives include the comparison of patient-reported and functional outcomes at short- and long-term follow-up. We will follow the patients for 5 years to track long-term effect. Assuming a difference in mean IPSS after treatment of 1 point with an SD of 5 and a non-inferiority margin set at the threshold for a clinically non-meaningful difference of + 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% dropout, the study will include 223 patients.
Discussion: In this first randomised clinical trial to compare two MISTs, we expect non-inferiority of PAE to TUMT. The most prominent problems with MIST BPH treatments are the unknown long-term effect and the lack of proper selection of candidates for a specific procedure. With analysis of the secondary outcomes, we aspire to contribute to a better understanding of durability and provide knowledge to guide treatment decisions.
Trial registration: ClinicalTrials.gov NCT05686525. Registered on January 17, 2023, https://clinicaltrials.gov/study/NCT05686525 .
{"title":"Non-inferiority, randomised, open-label clinical trial on the effectiveness of transurethral microwave thermotherapy compared to prostatic artery embolisation in reducing severe lower urinary tract symptoms in men with benign prostatic hyperplasia: study protocol for the TUMT-PAE-1 trial.","authors":"Anna Kristensen-Alvarez, Mikkel Fode, Hein Vincent Stroomberg, Kurt Krøyer Nielsen, Albert Arch, Lars Birger Lönn, Mikkel Taudorf, Steven John Widecrantz, Andreas Røder","doi":"10.1186/s13063-024-08409-x","DOIUrl":"10.1186/s13063-024-08409-x","url":null,"abstract":"<p><strong>Background: </strong>One-fourth of men older than 70 years have lower urinary tract symptoms (LUTS) that impair their quality of life. Transurethral resection of the prostate (TURP) is considered the gold standard for surgical treatment of LUTS caused by benign prostatic hyperplasia (BPH) that cannot be managed conservatively or pharmacologically. However, TURP is only an option for patients fit for surgery and can result in complications. Transurethral microwave thermotherapy (TUMT) and prostatic artery embolisation (PAE) are alternative minimally invasive surgical therapies (MISTs) performed in an outpatient setting. Both treatments have shown to reduce LUTS with a similar post-procedure outcome in mean International Prostate Symptom Score (IPSS). It is however still unknown if TUMT and PAE perform equally well as they have never been directly compared in a randomised clinical trial. The objective of this clinical trial is to assess if PAE is non-inferior to TUMT in reducing LUTS secondary to BPH.</p><p><strong>Methods: </strong>This study is designed as a multicentre, non-inferiority, open-label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments. The primary outcome is the IPSS of the two arms after 6 months. The primary outcome will be evaluated using a 95% confidence interval against the predefined non-inferiority margin of + 3 points in IPSS. Secondary objectives include the comparison of patient-reported and functional outcomes at short- and long-term follow-up. We will follow the patients for 5 years to track long-term effect. Assuming a difference in mean IPSS after treatment of 1 point with an SD of 5 and a non-inferiority margin set at the threshold for a clinically non-meaningful difference of + 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% dropout, the study will include 223 patients.</p><p><strong>Discussion: </strong>In this first randomised clinical trial to compare two MISTs, we expect non-inferiority of PAE to TUMT. The most prominent problems with MIST BPH treatments are the unknown long-term effect and the lack of proper selection of candidates for a specific procedure. With analysis of the secondary outcomes, we aspire to contribute to a better understanding of durability and provide knowledge to guide treatment decisions.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05686525. Registered on January 17, 2023, https://clinicaltrials.gov/study/NCT05686525 .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s13063-024-08411-3
Jennifer M Belus, Natalie E Johnson, Grace H Yoon, Nadine Tschumi, Malebanye Lerotholi, Irene Falgas-Bague, Tristan T Lee, Pearl Letsoela, Jessica F Magidson, Alain Amstutz, Niklaus D Labhardt
Background: The World Health Organization's (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below).
Methods: This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (Nplanned = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs < 50 years old). Follow-up assessments occur at 8, 20, and 32 weeks post-randomisation. The primary outcome is change in self-reported alcohol use (continuous AUDIT score), from baseline to 8 weeks follow-up. Change in the AUDIT from baseline to 20 and 32 weeks follow-up is a secondary outcome. Change in the biomarker phosphatidylethanol (secondary), liver enzyme values in serum (exploratory), and HIV viral load (for people with HIV only; exploratory) are also evaluated from baseline throughout the entire follow-up period. A linear regression model will be conducted for the primary analysis, adjusted for the stratification factors. Three a priori sensitivity analyses for the primary outcome are planned based on per protocol treatment attendance, recovery from unhealthy alcohol use, and clinically significant and reliable change.
Discussion: This trial will provide insight into feasibility and effectiveness of a shortened and primarily SMS supported version of mhGAP, which is especially relevant for settings where regular clinic attendance is a major barrier.
Trial registration: clinicaltrials.gov NCT05925270 . Approved on June 29th, 2023.
{"title":"SMSs as an alternative to provider-delivered care for unhealthy alcohol use: study protocol for Leseli, an open-label randomised controlled trial of mhGAP-Remote vs mhGAP-Standard in Lesotho.","authors":"Jennifer M Belus, Natalie E Johnson, Grace H Yoon, Nadine Tschumi, Malebanye Lerotholi, Irene Falgas-Bague, Tristan T Lee, Pearl Letsoela, Jessica F Magidson, Alain Amstutz, Niklaus D Labhardt","doi":"10.1186/s13063-024-08411-3","DOIUrl":"10.1186/s13063-024-08411-3","url":null,"abstract":"<p><strong>Background: </strong>The World Health Organization's (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below).</p><p><strong>Methods: </strong>This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (N<sub>planned</sub> = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs < 50 years old). Follow-up assessments occur at 8, 20, and 32 weeks post-randomisation. The primary outcome is change in self-reported alcohol use (continuous AUDIT score), from baseline to 8 weeks follow-up. Change in the AUDIT from baseline to 20 and 32 weeks follow-up is a secondary outcome. Change in the biomarker phosphatidylethanol (secondary), liver enzyme values in serum (exploratory), and HIV viral load (for people with HIV only; exploratory) are also evaluated from baseline throughout the entire follow-up period. A linear regression model will be conducted for the primary analysis, adjusted for the stratification factors. Three a priori sensitivity analyses for the primary outcome are planned based on per protocol treatment attendance, recovery from unhealthy alcohol use, and clinically significant and reliable change.</p><p><strong>Discussion: </strong>This trial will provide insight into feasibility and effectiveness of a shortened and primarily SMS supported version of mhGAP, which is especially relevant for settings where regular clinic attendance is a major barrier.</p><p><strong>Trial registration: </strong>clinicaltrials.gov NCT05925270 . Approved on June 29th, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-31DOI: 10.1186/s13063-024-08418-w
Rachel Phillips, Dongquan Bi, Beatriz Goulão, Marie Miller, Malak El-Askary, Oluyemi Fagbemi, Curie Freeborn, Maria Giammetta, Noura El Masri, Peter Flockhart, Manos Kumar, Mike Melvin, Dianne Murray, Anthony Myhill, Laila Saeid, Shanice Thomas, Graeme MacLennan, Victoria Cornelius
Background: Randomised controlled trials (RCTs) are typically designed to determine beneficial intervention effects. In addition, an important aspect of every trial is to collect data on any potential harmful effects, with the aim of ensuring that the benefit-risk balance is appropriate. The language used by trialists to describe these potential harmful effects is inconsistent. In pharmacological trials, researchers collect adverse events; when a causal relationship is suspected adverse events are further classified as adverse reactions. Academic researchers have moved to collectively refer to these as harm outcomes; the pharmaceutical industry refer to these events as safety outcomes. In trials of complex interventions, phrases such as unintended consequences or effects are used. With the inconsistent use of terminology by researchers and the potential benefits to be gained from harmonising communications, we sought public opinion on terminology used to describe harmful effects and how these outcomes are communicated in the scientific literature, as well as in public facing material on medications.
Methods: We held two in-person public involvement meetings with public partners, in London and Aberdeen in 2023. Both meetings followed a pre-specified format. We provided a background to the topic including the information researchers collect on potential harms in clinical trials and shared examples on how this information gets presented in practice. We then discussed public partners' perspectives on terminology used and communication of intervention harm in academic journals and in public facing materials. A summary of these discussions and the main topics raised by public partners are presented.
Results: Public partners endorsed the use of different terms for different situations, preferring the use of 'side-effect' across all contexts and reserving the use of 'harm' to indicate more severe events. Generally, public partners were happy with the type of information presented in public facing materials but discussions revealed that presentation of information on public NHS websites led to misconceptions about harm.
Conclusion: This work provides a starting point on preferred terminology by patients and the public to describe potential harmful intervention effects. Whilst researchers have tried to seek agreement, public partners endorsed use of different terms for different situations. We highlight some key areas for improvement in public facing materials that are necessary to avoid miscommunication and incorrect perception of harm.
{"title":"Public perspective on potential treatment intervention harm in clinical trials-terminology and communication.","authors":"Rachel Phillips, Dongquan Bi, Beatriz Goulão, Marie Miller, Malak El-Askary, Oluyemi Fagbemi, Curie Freeborn, Maria Giammetta, Noura El Masri, Peter Flockhart, Manos Kumar, Mike Melvin, Dianne Murray, Anthony Myhill, Laila Saeid, Shanice Thomas, Graeme MacLennan, Victoria Cornelius","doi":"10.1186/s13063-024-08418-w","DOIUrl":"https://doi.org/10.1186/s13063-024-08418-w","url":null,"abstract":"<p><strong>Background: </strong>Randomised controlled trials (RCTs) are typically designed to determine beneficial intervention effects. In addition, an important aspect of every trial is to collect data on any potential harmful effects, with the aim of ensuring that the benefit-risk balance is appropriate. The language used by trialists to describe these potential harmful effects is inconsistent. In pharmacological trials, researchers collect adverse events; when a causal relationship is suspected adverse events are further classified as adverse reactions. Academic researchers have moved to collectively refer to these as harm outcomes; the pharmaceutical industry refer to these events as safety outcomes. In trials of complex interventions, phrases such as unintended consequences or effects are used. With the inconsistent use of terminology by researchers and the potential benefits to be gained from harmonising communications, we sought public opinion on terminology used to describe harmful effects and how these outcomes are communicated in the scientific literature, as well as in public facing material on medications.</p><p><strong>Methods: </strong>We held two in-person public involvement meetings with public partners, in London and Aberdeen in 2023. Both meetings followed a pre-specified format. We provided a background to the topic including the information researchers collect on potential harms in clinical trials and shared examples on how this information gets presented in practice. We then discussed public partners' perspectives on terminology used and communication of intervention harm in academic journals and in public facing materials. A summary of these discussions and the main topics raised by public partners are presented.</p><p><strong>Results: </strong>Public partners endorsed the use of different terms for different situations, preferring the use of 'side-effect' across all contexts and reserving the use of 'harm' to indicate more severe events. Generally, public partners were happy with the type of information presented in public facing materials but discussions revealed that presentation of information on public NHS websites led to misconceptions about harm.</p><p><strong>Conclusion: </strong>This work provides a starting point on preferred terminology by patients and the public to describe potential harmful intervention effects. Whilst researchers have tried to seek agreement, public partners endorsed use of different terms for different situations. We highlight some key areas for improvement in public facing materials that are necessary to avoid miscommunication and incorrect perception of harm.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1186/s13063-024-08401-5
Kathryn M Yount, Daniel J Whitaker, Xiangming Fang, Quach Thu Trang, Meghan Macaulay, Tran Hung Minh
Background: Globally, women 15-24 years are at heightened risk of sexual violence victimization, a risk factor for adverse mental, physical, and behavioral health outcomes. Sexual violence is common at universities and most often perpetrated by men, yet few evidence-based prevention strategies targeting men have been tested in low- and middle-income countries. GlobalConsent is a six-module, web-based educational program adapted from an efficacious U.S.-based program. Nine months post-treatment in a randomized trial in Vietnam, GlobalConsent reduced men's sexually violent behavior (odds ratio [OR] = 0.71, 95%CI 0.50-1.00) and increased prosocial intervening behavior (OR = 1.51, 1.00-2.28) relative to an attention-control. Evidence regarding optimal implementation strategies for scale up is needed.
Methods: We will randomize six medical universities in North, Central, and South Vietnam to deliver GlobalConsent using two different packages of implementation strategies that vary in intensity. Higher-intensity strategies will include greater (1) pre- and post-implementation engagement with university leaders and faculty and (2) greater pre-implementation outreach, follow-up, and incentives for students to promote engagement and completion of GlobalConsent. Higher intensity universities will receive additional training and support for their added activities. We will compare implementation drivers and outcomes, intervention effectiveness, and cost-effectiveness across the two implementation bundles. Our mixed-methods comparative interrupted time series design includes (1) qualitative interviews and quantitative surveys with university leaders and implementation teams to assess implementation barriers and facilitators; (2) repeated surveys with leaders and faculty, implementation teams, and male students to assess multilevel implementation drivers and outcomes; (3) repeated surveys with male students to assess behavioral outcomes (sexual violence and intervening behavior) and mediating variables (knowledge, attitudes, affect, and capacities); and (4) time diaries and cost tracking to assess cost-effectiveness of the two implementation-strategies bundles.
Discussion: This project is the first to assess packages of implementation strategies to deliver an efficacious web-based sexual violence prevention program for undergraduate men across all regions of Vietnam and synergizes with a violence-prevention training initiative (D43TW012188). This approach will produce rigorous evidence about how to disseminate GlobalConsent nationally, which holds promise to reduce gender-based health inequities linked to sexual violence as GlobalConsent is brought to scale.
Trial registration: NCT06443541. Retrospectively registered with ClinicalTrials.gov. Registered on June 05, 2024.
{"title":"Strategies for Implementing GlobalConsent to Prevent Sexual Violence in University Men (SCALE): study protocol for a national implementation trial.","authors":"Kathryn M Yount, Daniel J Whitaker, Xiangming Fang, Quach Thu Trang, Meghan Macaulay, Tran Hung Minh","doi":"10.1186/s13063-024-08401-5","DOIUrl":"10.1186/s13063-024-08401-5","url":null,"abstract":"<p><strong>Background: </strong>Globally, women 15-24 years are at heightened risk of sexual violence victimization, a risk factor for adverse mental, physical, and behavioral health outcomes. Sexual violence is common at universities and most often perpetrated by men, yet few evidence-based prevention strategies targeting men have been tested in low- and middle-income countries. GlobalConsent is a six-module, web-based educational program adapted from an efficacious U.S.-based program. Nine months post-treatment in a randomized trial in Vietnam, GlobalConsent reduced men's sexually violent behavior (odds ratio [OR] = 0.71, 95%CI 0.50-1.00) and increased prosocial intervening behavior (OR = 1.51, 1.00-2.28) relative to an attention-control. Evidence regarding optimal implementation strategies for scale up is needed.</p><p><strong>Methods: </strong>We will randomize six medical universities in North, Central, and South Vietnam to deliver GlobalConsent using two different packages of implementation strategies that vary in intensity. Higher-intensity strategies will include greater (1) pre- and post-implementation engagement with university leaders and faculty and (2) greater pre-implementation outreach, follow-up, and incentives for students to promote engagement and completion of GlobalConsent. Higher intensity universities will receive additional training and support for their added activities. We will compare implementation drivers and outcomes, intervention effectiveness, and cost-effectiveness across the two implementation bundles. Our mixed-methods comparative interrupted time series design includes (1) qualitative interviews and quantitative surveys with university leaders and implementation teams to assess implementation barriers and facilitators; (2) repeated surveys with leaders and faculty, implementation teams, and male students to assess multilevel implementation drivers and outcomes; (3) repeated surveys with male students to assess behavioral outcomes (sexual violence and intervening behavior) and mediating variables (knowledge, attitudes, affect, and capacities); and (4) time diaries and cost tracking to assess cost-effectiveness of the two implementation-strategies bundles.</p><p><strong>Discussion: </strong>This project is the first to assess packages of implementation strategies to deliver an efficacious web-based sexual violence prevention program for undergraduate men across all regions of Vietnam and synergizes with a violence-prevention training initiative (D43TW012188). This approach will produce rigorous evidence about how to disseminate GlobalConsent nationally, which holds promise to reduce gender-based health inequities linked to sexual violence as GlobalConsent is brought to scale.</p><p><strong>Trial registration: </strong>NCT06443541. Retrospectively registered with ClinicalTrials.gov. Registered on June 05, 2024.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}