Trials最新文献

There are good practical reasons to use electronic consent (e-consent) in randomised trials, especially when conducting large-scale clinical trials to answer population-level health research questions. However, determining ethical reasons for e-consent is not so clear and depends on a proper understanding of what e-consent means when used in clinical trials and its ethical significance. Here we focus on four features of ethical significance which give rise to a range of ethical considerations relating to e-consent and merit further focused ethics research.

Background: Postoperative atrial fibrillation (POAF) is a common and potentially serious complication post cardiac surgery. Hypomagnesaemia is common after cardiac surgery and recent evidence indicates that supplementation of magnesium may prevent POAF. We aim to investigate the effectiveness of continuous intravenous magnesium sulphate administration in the perioperative period to prevent POAF as compared to placebo.

Methods: The (POMPAE) trial is a phase 2, single-center, double-blinded randomized superiority clinical study. It aims to assess the impact of perioperative continuous intravenous magnesium administration on the occurrence of cardiac surgery-related POAF. A total of 530 patients will be included. Eligible patients will be randomized in 1:1 ratio to the intervention or placebo group with stratification based on the presence of valvular surgery. The objective of the infusion is to maintain ionized magnesium levels between 1.5 and 2.0 mmol/L.

Discussion: The primary outcome measure is the incidence of de novo POAF within the first 7 days following surgery, with censoring at hospital discharge. This trial may generate crucial evidence for the prevention of POAF and reduce clinical adverse events in patients following cardiac surgery.

Trial registration: The POMPAE trial was registered at ClinicalTrials.gov under the following identifier NTC05669417, https://clinicaltrials.gov/ct2/show/NCT05669417 . Registered on December 30, 2022.

Protocol version: Version 3.3, dated 13-01-2023.

Background: Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient's quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD.

Methods: To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23-7938; December 4, 2023). Recruitment start: March 2024.

Discussion: Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias.

Trial registration: German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. STUDY PROTOCOL VERSION 10: Version 1.2; 12 June 2024.

Background: Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients' limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients' physical function and the burden of caregivers.

Methods/design: A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training.

Discussion: Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden.

Trial registration: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.

Background: Ultrasound-guided supraclavicular block (UGSCB) is an emerging technique gaining interest amongst emergency physicians that provides regional anaesthesia to the upper limb to tolerate painful procedures. It offers an alternative to the more traditional technique of a Bier block (BB). However, the effectiveness or safety of UGSCB when performed in the emergency department (ED) is unclear.

Methods: SUPERB (SUPraclavicular block for Emergency Reduction versus Bier block) is a prospective open-label non-inferiority randomised controlled trial comparing the effectiveness of UGSCB versus BB for closed reduction of upper limb fractures and/or dislocations. Adult patients presenting with upper limb fracture and/or dislocation requiring closed reduction in ED were randomised to either UGSCB or BB. Once regional anaesthesia is obtained, closed reduction of the injured part was performed and immobilised. The primary outcome is maximal pain experienced during closed reduction measured via a visual analogue scale (VAS). Secondary outcomes include post-reduction pain, patient satisfaction, total opioid requirement in ED, ED length of stay, adverse events and regional anaesthesia failure.

Results: Primary outcome analysis will be performed using both the intention-to-treat and per-protocol populations. The between-group difference in maximum pain intensity will be assessed using linear regression modelling with trial group allocation (UGSCB vs BB) included as a main affect. A pre-specified non-inferiority margin of 20 mm on the VAS scale will be used to establish non-inferiority of UGSCB compared to BB.

Conclusion: SUPERB is the first randomised controlled trial to investigate the effectiveness and safety of UGSCB in the ED. The trial has the potential to demonstrate that UGSCB is an alternative safe and effective option for the management of upper extremity emergencies in the ED.

Background: Low back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients' mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients.

Methods: This is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (< 75 years old) will be at a ratio of 1:2. The primary outcome is the time required for the visual analogue scale (VAS) score to decline by ≥ 10 from baseline. The secondary outcome is the changes in VAS scores from baseline, the frequency and dosage of rescue medication, BTMs, bone mineral density (BMD), and variations in upper gastrointestinal (GI) symptom scores from baseline (including heartburn, pain, and bloating).

Discussion: This study will provide objective evidence for the efficiency and safety of minodronate. Furthermore, it will be helpful to evaluate the quantitative relationship between BTMs and BMD in patients with osteoporosis under different ages.

Trial registration: This study protocol has been registered with ClinicalTrials.gov ID NCT05645289 ( https://clinicaltrials.gov/search?term=NCT05645289 ) on December 8, 2022. The registry name is Peking University Third Hospital. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2022465, 2022.08.09, V2.0). The results will be published in scientific peer-reviewed journals.

Trial status: The protocol was registered at ClinicalTrials.gov (registration number: NCT05645289). Recruitment has started in January 2023 and is still ongoing.

Background: Breast cancer is a prevalent form of cancer among women worldwide, often accompanied by physical and psychological side effects due to the disease and the treatment's aggressiveness. Regular physical exercise has emerged as a non-pharmacological approach to improve the quality of life of breast cancer survivors. We herein report the protocol of the WaterMama Study, which aims to evaluate the effects of land- or water-based aerobic exercise programs, compared to a health education program, on cancer-related fatigue and other health-related outcomes in breast cancer survivors.

Methods: The WaterMama trial is a randomized, single-blinded, three-arm, parallel, superiority trial. We aim to recruit 48 women ≥ 18 years of age who have completed primary treatment for stage I-III breast cancer. Participants are randomly allocated in a 1:1:1 ratio to 12-week interventions of aerobic exercise training programs either in the aquatic or land environment (two weekly 45-min sessions) plus health education (a weekly 45-min session), or an active-control group receiving health education alone (a weekly 45-min session). The primary outcome is cancer-related fatigue, and the secondary outcomes include cardiorespiratory fitness, muscular performance, muscle morphology, functional capacity, mental health, cognitive function, pain, and quality of life. Outcomes assessments are conducted before and after the 12-week intervention period. The analysis plan will employ an intention-to-treat approach and per protocol criteria.

Discussion: Our conceptual hypothesis is that both aerobic exercise programs will positively impact primary and secondary outcomes compared to the health education group alone. Additionally, due to its multi-component nature, we expect the aquatic exercise program promote more significant effects than the land exercise program on cancer-related fatigue, muscular outcomes, and pain.

Trial registration: The study was prospectively registered at ClinicalTrials.gov NCT05520515. Registered on August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05520515.

Background: Knee osteoarthritis (KOA) presents a prevalent orthopedic condition causing substantial impairment in the quality of life and imposing a significant societal and economic burden. Mesenchymal stromal/stem cells (MSCs), known for their regenerative properties and immunomodulatory effects, have emerged as a promising therapeutic avenue in regenerative medicine. Despite MSCs' therapeutic potential, their precise mechanisms of action in KOA remain underexplored.

Methods: Conducted as a randomized, open-label clinical trial, 20 patients will be enrolled, with 10 in the intervention group and 10 in the control group. The primary focus will be to explore the molecular mechanisms associated with MSC therapy. Biomarkers and gene expressions related to cartilage metabolism, inflammation, immune modulation, and pain in the synovial fluid, blood, and tissue samples will be analyzed. Patients will undergo pre- and post-treatment evaluations using patient-reported outcome measures (PROMs) and comprehensive clinical assessments.

Discussion: This is an exploratory study with the goal to provide comprehensive insights into the therapeutic effects of MSCs on a molecular level, potentially paving the way for optimized and more effective MSC-based therapies in the management of KOA, as well as furthering the development of novel treatment strategies.

Trial registration: ClinicalTrials.gov, NCT06078059. Registered on 5 October 2023.

Background: In cardiac surgical procedures, patients carrying high-risk profiles are prone to encompass complicated cardiopulmonary bypass (CPB) separation. Intraoperative transesophageal echocardiography (TEE), a readily available tool, is utilized to detect cardiac structural and functional pathologies as well as to facilitate clinical management of CPB separation, especially in the episodes of hemodynamic compromise. However, the conventional TEE examination, always performed in a liberal fashion without any restriction of view acquisition, is relatively time-consuming; there appear its flaws in the context of critically severe status. We therefore developed the perioperative rescue transesophageal echocardiography (PReTEE), a simplified three-view TEE protocol consisting of midesophageal four chamber, midesophageal left ventricular long axis, and transgastric short axis.

Methods: This is a single-center and randomized controlled trial which will be implemented in Peking Union Medical College Hospital, Beijing, China. A total of 46 TEE scans are schemed to be performed by 6 operators participating in and randomly assigned to either the PReTEE or the conventional TEE group. This study is purposed to investigate whether the efficiency of discriminating leading causes of difficult CPB wean-off can be significantly improved via an abbreviated sequence of TEE views. The primary outcome of interest is the difference between the groups of PReTEE and the conventional TEE in the successful discrimination of etiologies in specified 120 s. Cox proportional hazards model will be further employed to calculate the outcome difference.

Discussion: The estimated results of this trial are oriented at verifying whether a simplified TEE exam sequence can improve the efficiency of etiologies discrimination during CPB separation in cardiac surgery.

Trial registration: ClinicalTrials.gov NCT05960552. Registered on 6 July 2023.

Objective: To assess the cost-effectiveness of using cheaper-but-noisier outcome measures, such as a short questionnaire, for large simple clinical trials.

Background: To detect associations reliably, trials must avoid bias and random error. To reduce random error, we can increase the size of the trial and increase the accuracy of the outcome measurement process. However, with fixed resources, there is a trade-off between the number of participants a trial can enrol and the amount of information that can be collected on each participant during data collection.

Methods: To consider the effect on measurement error of using outcome scales with varying numbers of categories, we define and calculate the variance from categorisation that would be expected from using a category midpoint; define the analytic conditions under which such a measure is cost-effective; use meta-regression to estimate the impact of participant burden, defined as questionnaire length, on response rates; and develop an interactive web-app to allow researchers to explore the cost-effectiveness of using such a measure under plausible assumptions.

Results: An outcome scale with only a few categories greatly reduced the variance of non-measurement. For example, a scale with five categories reduced the variance of non-measurement by 96% for a uniform distribution. We show that a simple measure will be more cost-effective than a gold-standard measure if the relative increase in variance due to using it is less than the relative increase in cost from the gold standard, assuming it does not introduce bias in the measurement. We found an inverse power law relationship between participant burden and response rates such that a doubling the burden on participants reduces the response rate by around one third. Finally, we created an interactive web-app ( https://benjiwoolf.shinyapps.io/cheapbutnoisymeasures/ ) to allow exploration of when using a cheap-but-noisy measure will be more cost-effective using realistic parameters.

Conclusion: Cheaper-but-noisier questionnaires containing just a few questions can be a cost-effective way of maximising power. However, their use requires a judgement on the trade-off between the potential increase in risk of information bias and the reduction in the potential of selection bias due to the expected higher response rates.