Trials最新文献

Background: Acute respiratory distress syndrome (ARDS) is the acute hypoxemic respiratory failure that presents with non-cardiogenic pulmonary opacities. Patients receiving non-invasive respiratory support might present with high transpulmonary pressure, pulmonary strain, and pendelluft, which contribute to the development of patient self-inflicted lung injury (P-SILI). Experimental studies have identified that continuous positive airway pressure (CPAP) is successful in attenuating P-SILI effectors compared to high-flow nasal oxygenation (HFNO). However, it remains uncertain whether this attenuation is associated with a reduction in lung injury and improved clinical outcomes.

Methods: This is a multicenter, randomized, open-label, controlled trial. One hundred and twenty non-intubated patients with established ARDS will be randomly assigned to receive non-invasive respiratory support with either CPAP 12 cmH₂O or HFNO 50 L/min for 48 h. The primary outcome is biological lung injury, assessed with plasma levels of the epithelial pulmonary dysfunction biomarker sRAGE (soluble Receptor of Advanced Glycation End-products). Secondary outcomes include plasmatic pulmonary dysfunction biomarkers, P-SILI effectors (pulmonary strain, pendelluft, transpulmonary pressure), 48-h tracheal intubation rate, 90-day tracheal intubation rate, and 90-day mortality. All analyses will be conducted according to the intention-to-treat principle.

Discussion: This study will assess the potential role of CPAP in attenuating P-SILI effectors and inflicting less biological lung injury compared to HFNO. This physiologic effect may lead to lower rates of tracheal intubation and mortality. This project will provide new knowledge on the respiratory management of non-intubated ARDS patients, a subject where evidence is lacking.

Trial registration: ClinicalTrials.gov NCT06694311. Registered on 18 November 2024 as HCB/2023/1105.

Background: Movement-evoked pain following pancreatectomy is often severe and inadequately controlled by conventional analgesic regimens. Transcutaneous electrical acupoint stimulation (TEAS), a non-invasive technique derived from acupuncture, has shown promise in reducing postoperative pain and opioid consumption. However, the efficacy of extended perioperative TEAS-particularly its sustained application through the early postoperative period-has not been evaluated in patients undergoing pancreatectomy.

Methods: This will be a prospective, single-center, two-arm, randomised controlled trial. A total of 132 patients undergoing pancreatectomy will be randomised allocated to the TEAS and the Sham TEAS groups. The TEAS group will receive stimulation (5-30mA, the stimulation intensity will be adjusted in accordance with the maximal level tolerated by each patient, 2/100 Hz alternating, on the Neiguan (PC6), Zusanli (ST36), Hegu (LI4) and Waiguan (SJ5)) from 30 min before anesthesia for 30min and repeated on the first 1,2 and 3 days after surgery. The patients in the Sham TEAS group will receive electrodes applied, but will receive no stimulation. The primary outcome is the highest movement-evoked pain intensity during 72 h postoperatively, assessed by the numeric rating scale (NRS). The secondary outcomes include the highest movement-evoked pain at rest, morphine consumption, recovery quality, and sleep quality over 72 h postoperatively and levels of inflammatory factors. All statistical analyses will be performed based on the modified intention-to-treat principle.

Discussion: This study aims to evaluate whether continuous TEAS during perioperative period (administered from 30 min before induction of anesthesia through 72 h postoperatively) will reduce the movement-evoked pain during postoperative 72 h in patients undergoing pancreatectomy. The findings may offer evidence for an effective opioid reducing anesthesia strategy that enhances analgesia and supports recovery, with potential value for broader clinical application.

Trial registration: ClinicalTrials.gov, NCT06541561. Registered on 2 August 2024.

Background: In Kenya, as in many African countries, private pharmacies are ubiquitous, frequently accessed, and underutilized for the delivery of HIV prevention services. Whether enabling private pharmacies to initiate and manage clients on HIV pre- and post-exposure prophylaxis (PrEP and PEP) leads to greater uptake and continuation than the current standard-pharmacy referral to clinic-based PrEP/PEP-is unknown. To address this gap and inform how private pharmacies might partner with the public sector, we are testing several models of pharmacy-delivered PrEP/PEP in comparison to the current standard.

Methods: The Pharm PrEP cRCT is a 60-pharmacy, four-arm cluster-randomized controlled trial ongoing in Central and Western Kenya (first enrollment: 26 June 2023). Eligible pharmacies were licensed by the government, had a private room, and were willing to complete research activities (including a 3-day provider training). Study pharmacies were randomized 1:1:1:1 to (1) client-sustained delivery, in which clients pay pharmacies 250 KES (~$2 USD) per PrEP/PEP visit; (2) implementor-sustained delivery, in which clients pay nothing and implementors pay pharmacies 250 KES per PrEP/PEP visit; (3) implementor-sustained + counselor-supported delivery, in which clients pay nothing, delivery is supported by an HIV testing services (HTS) counselor, and implementors pay pharmacies 100 KES (~$1 USD) per PrEP/PEP visit; or 4) referral (control), in which clients pay nothing and implementors pay pharmacies 100 KES per referral to clinic-based PrEP/PEP. Pharmacies delivering PrEP/PEP receive supporting commodities free from government stock. Primary outcomes are PrEP initiation and continuation (any refilling) reported by clients 60 days post-enrollment; secondary outcomes include PEP initiation, PEP-to-PrEP transition, repeat PEP use, PrEP/PEP initiation, and PrEP/PEP continuation at 60 and 270 days post-enrollment. Primary analyses will compare each intervention arm to the control; secondary analyses will compare intervention arms to one another. We will additionally assess implementation outcomes (e.g., acceptability, feasibility, cost) from client and provider perspectives.

Discussion: This trial will generate evidence on the potential benefits of leveraging private pharmacies for delivery of PrEP and PEP and the relative effectiveness of pharmacy delivery when subsidized by clients, implementors, and/or supported by HTS counselors. The findings may inform enabling policy and approaches for scale-up.

Trial registration: ClinicalTrials.gov NCT05842122. Registered on April 5, 2023.

Background: Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the Western world, with an estimated 40,000 newly diagnosed cases in the UK every year. Early detection and treatment of nAMD are important to achieve good visual acuity and quality-of-life (QoL) outcomes. Whilst early treatment of the second eye, following detection using optical coherence tomography (OCT) imaging, has shown maintenance of visual acuity and health-related QoL and reduced health and social care costs, there is a paucity of information about the benefits of early detection of nAMD in the first eye. In particular, although it is reasonable to consider a form of targeted screening of those most likely to develop nAMD, it is unclear if those invited would adhere to such a programme.

Methods: In this randomized controlled trial, 130 participants will be recruited from community-based eye healthcare practices within the UK whilst attending their routine appointment. Participants will be randomized to either a standard care arm to attend a further follow-up appointment at 12 months, or an intervention arm, attending every 3 months for assessment. The end of study is at 12 months. All participants will complete the NEI-VFQ-25, MacDQoL, PHQ9 and EQ-5D-3L questionnaires at baseline and 12 months. In addition, all participants and recruiting investigators will complete the Theoretical Framework of Acceptability questionnaire at 12 months.

Discussion: The DORADO study aims to assess the persistence and adherence to and acceptability of a community-based programme for the early detection of nAMD.

Trial registration: ISRCTN10005321. Registered on 08 November 2024.

Background: Insomnia symptoms during the perinatal period are prevalent and may contribute to negative mental health and birthing outcomes. Cognitive Behavioural Therapy for Insomnia (CBT-I) is a non-pharmacological therapy efficacious in the treatment of insomnia. Previous studies have shown the effectiveness of digital CBT-I during the perinatal period. However, to date, our understanding of whether this treatment can be effectively implemented in community perinatal care is limited.

Methods: In this two-arm hybrid effectiveness-implementation type 1 randomised controlled trial (RCT), eligible pregnant individuals with self-reported insomnia symptoms (Insomnia Severity Index > 7) will be randomised to either the CBT-I intervention (Healthy Sleep Program) or active control (sleep hygiene education). The primary outcome is maternal insomnia symptom severity at (i) one pregnancy endpoint and (ii) averaged across three times post birth for the postpartum endpoint. An economic evaluation will assess cost-effectiveness. Barriers and enablers to sustained implementation will be explored using the Theoretical Domains Framework and the Practical Robust Implementation and Sustainability Model.

Discussion: This study will offer an understanding of the effectiveness, cost-effectiveness, and sustained implementation potential of a digital sleep health program in perinatal care. These outcomes will provide empirical evidence to inform broader implementation of a scalable sleep program to improve insomnia symptoms in perinatal populations.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12622000940774. Registered on 01/07/2022.

Background: Subthalamic deep brain stimulation (STN-DBS) effectively treats motor symptoms in appropriately selected patients with Parkinson's disease, but individual responses vary. Despite modern directional leads allowing more precise stimulation, optimal contact selection strategies have not yet been standardized. This study compares a standardized imaging-guided contact selection protocol to conventional clinical programming.

Methods: We designed a monocentric, randomized, double-blind crossover trial enrolling 30 people with Parkinson's disease with bilateral directional STN-DBS. Participants will undergo both programming approaches: standardized imaging-guided contact selection targeting the dorsolateral STN and conventional contact selection through clinical test stimulations. Each configuration will be applied for 1 week. The primary outcome is patient preference after both treatments. Secondary outcomes include motor assessments (MDS-UPDRS III), accelerometric monitoring, and questionnaire-based quality of life measures (e.g., PDQ-39).

Discussion: This study addresses a critical gap in standardization of imaging-guided DBS programming. By using patient preference as the primary outcome, we aim to capture clinically meaningful differences that may not be detected with traditional motor scales. The crossover design balances statistical power with clinical feasibility in specialized care settings.

Trial registration: Deutsches Register für Klinische Studien DRKS00034229. Registered on May 27, 2024.

Objectives: Cognitive behavioral therapy for insomnia (CBT-I) will be compared with hormone replacement therapy (HRT) and sleep hygiene (active control treatment).

Background: The late menopausal transition is a vulnerable hormonal phase for women, where sleep disorders and vasomotor symptoms affect one out of three women. HRT is probably the most commonly used method to treat menopausal symptoms, including sleep problems. However, CBT-I is considered the treatment of choice for insomnia in adults in general. Despite this fact, there are only a few studies that have examined the effect of CBT-I in peri- and postmenopause and only one observational study comparing CBT-I and HRT for perimenopausal insomnia. Therefore, this study aims to compare the efficacy of HRT and CBT-I on subjective and objective sleep quality.

Methods: Fifty-four late perimenopausal women will be randomly assigned to receive psychotherapist-led CBT-I, HRT (transdermal estradiol 1.5 mg/d and oral micronized progesterone 200 mg/day), or sleep hygiene (active control). Sleep quality will be continually assessed for 3 months, using validated questionnaires and an in-ear EEG device. Moreover, potential changes in the biofunctional status and age (27) and vasomotor symptoms will be assessed.

Discussion: The goal is to enable evidence-based treatment decisions for affected women to close the menopausal medical care gap and improve women's quality of life. TRIAL REGISTRATION {2A, 2B}: The study has been registered at ClinicalTrials.gov (Identifier: NCT06497894) on 11 July 2024. URL: (https://clinicaltrials.gov/ct2/show/NCT06497894). PROTOCOL VERSION AND TRIAL STATUS {3}: Protocol version 3.1 (30. April 2024). Recruitment has not started yet (15. August 2024). The recruitment is planned to begin on 01. November 2024, with an estimated completion date of 01. April 2026.

Background: Trocar-site hernia is an underappreciated condition with estimates of approximately 25% at 2 years follow-up. Duramesh™ has emerged as a novel product with potential benefits for incisional hernia prevention. The aim of this trial is to establish if Duramesh is superior to conventional suture for prevention of periumbilical trocar-site hernia following laparoscopic surgery.

Methods: The TROCAR trial is a prospective single-centre, parallel arm, double-blind randomised controlled trial conducted in the United Kingdom. A total of 250 randomised participants (1:1 ratio) will be allocated to receive either Duramesh or conventional suture (J-vicryl or J-PDS). The primary outcome is the cumulative incidence of sonographically detected periumbilical trocar-site hernia at 2 years of the index operation. Secondary outcomes are 90-day surgical site occurrence (SSO), 90-day surgical site infection (SSI), 90-day rate of reoperation, 90-day mortality, length of hospital stay, and quality of life at 3 months, 1 year and 2 years measured using a modified EuraHS-QoL score and modified Carolinas Comfort Scale.

Conclusion: TROCAR will provide level 1 evidence on trocar-site hernia prevention in both the emergency and elective settings.

Trial registration: Registration number ISRCTN14473961 (https://doi.org/10.1186/ISRCTN14473961). Registered on 14th April 2025.

Background: Infants born extremely preterm (EP; < 28 weeks of gestation) or term born infants with hypoxic-ischemic encephalopathy (HIE) have increased risk of long-term cognitive and learning deficits. Early supplementation with long chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), choline, uridine-5'-monophosphate (UMP), and cytidine-5'-monophosphate (CMP), zinc, iodine, and vitamin B12 may improve cognitive and language outcomes in these populations.

Methods: This multicentre, blinded, stratified, randomised controlled trial, including an economic evaluation, will investigate the impact of nutritional supplementation on cognitive development in infants born EP or term born infants with HIE. The planned sample size is 1010 (538 EP, and 472 HIE) infants from up to 40 National Health Service neonatal units in the UK. The trial patient populations are infants born EP (preterm stratum) and term infants (born at or more than 35 weeks of gestation) with HIE who received therapeutic hypothermia (HIE stratum). Patient strata were chosen to include infants at high risk of adverse neurodevelopmental outcomes by virtue of EP birth, or HIE requiring therapeutic hypothermia. Infants are randomly assigned, in a 1:1 allocation ratio, to receive either the active supplement or a matched control, in addition to standard care. Families, clinical teams, investigators, and Clinical Trials Unit staff are blinded to allocation. Only the Senior Trials Programmer and Trial Statisticians have access to allocation information. The active supplement is a nutrient powder formulated to be mixed with breast milk, infant formula, or food, containing LCPUFAs (including DHA, EPA, and ARA), choline, UMP, CMP, zinc, iodine, and vitamin B12. Supplementation commences once infants achieve full milk feeds and continues until 12 months post-estimated date of delivery (EDD), with a daily dosage of 1 g per kilogram of body weight. The primary outcome is the Parent Report of Children's Abilities-Revised non-verbal cognitive scale at 24 months post-EDD. EP and HIE patient population comparisons have been appropriately powered and will be analysed separately.

Discussion: Findings from the DOLFIN trial will inform international neonatal and infant nutritional and feeding policy and practice. Learnings from the trial will inform the design and delivery of future neonatal nutritional intervention trials.

Trial registration: ISRCTN62323236. Registered 16 May 2022, https://www.isrctn.com/ISRCTN62323236 .

Background: Hypertension (HTN) is a major non-communicable disease worldwide, including in Uganda. Studies have estimated HTN prevalence in Uganda between 19 and 33% among adults, with only 7-9% controlled within clinical target ranges. Isometric handgrip training (IHT), a form of resistance training that consists of performing multiple static forearm contractions separated by brief rest periods on a handgrip dynamometer or stress ball, is a promising simple, time-efficient, and low-cost intervention. This randomized controlled trial (RCT) aims to determine the efficacy of 12 weeks of IHT compared to standard of care on resting blood pressure (BP) levels in a population of hypertensive patients at the Soft Power Mukagwa Allan Stone Community Health Clinic (Kyabirwa, Uganda).

Methods: This study consists of a two-arm, parallel, randomized controlled, superiority trial. Patients having (1) a diagnosis of stage 1 HTN (BP > 140-159/90-99 mmHg), (2) not currently taking HTN medication, (3) not having been on HTN medication in the past 3 months, and (4) aged ≥18 years will be recruited. A total of 250 participants will be randomized with equal allocation to intervention and control arms. The control arm will receive standard care for HTN for a duration of 12 weeks, as per clinic standard practice. In addition to standard care, the intervention arm will perform IHT sessions three times a week for a duration of 12 weeks. IHT sessions will consist of four 2-min isometric handgrip contractions, using alternate hands with 1-min rest periods between contractions (total: 12 min). The primary outcome is the mean resting systolic BP at 12 weeks. Data collection will be conducted at baseline, 1, 2, and 3 months and will include measurements of BP levels and administration of questionnaires.

Discussion: This RCT will provide evidence on the efficacy of IHT, a promising and cost-efficient therapy for blood pressure control in a Ugandan context. We anticipate that our results will inform treatment strategies for hypertensive patients in Uganda and in other high-burden LMIC contexts.

Trial registration: Retrospectively registered. ISRCTN Registry; ISRCTN46005092 ; 31/10/2024.