A longitudinal assessment of trial protocols approved by research ethics committees: The Adherance to SPIrit REcommendations in the UK (ASPIRE-UK) study

AIDS

Objectives:This study aimed to investigate the association of demographic and clinical characteristics, including HIV-specific parameters with the antibody response to a third dose of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in people with HIV-1 (PWH).Design:Post hoc analysis of data collected during the observational extension of the COrona VaccinE tRiAL pLatform trial (COVERALL-2) nested into the Swiss HIV Cohort Study (SHCS).Methods:Serological measurements were conducted on a total of 439 PWH who had received a third dose of either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. Antibody reactivity was assessed using the multifactorial ABCORA immunoassay that defines SARS-CoV-2 seroconversion and predicts neutralization activity. The association between log transformed antibody reactivity and various baseline factors …

The Lancet Rheumatology

BackgroundMethotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.MethodWe did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants …

Journal of the College of Community Physicians of Sri Lanka

ImportanceMendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation.ObjectiveTo develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies.Design, Setting, and ParticipantsThe development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design …

Bone & joint open

Aims The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial. Methods Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale …

ImportancePlatform trials have become increasingly common, and evidence is needed to determine how this trial design is actually applied in current research practice.ObjectiveTo determine the characteristics, progression, and output of randomized platform trials.Evidence ReviewIn this systematic review of randomized platform trials, Medline, Embase, Scopus, trial registries, gray literature, and preprint servers were searched, and citation tracking was performed in July 2022. Investigators were contacted in February 2023 to confirm data accuracy and to provide updated information on the status of platform trial arms. Randomized platform trials were eligible if they explicitly planned to add or drop arms. Data were extracted in duplicate from protocols, publications, websites, and registry entries. For each platform trial, design features such as the use of a common control arm, use of nonconcurrent control data …

Eclinicalmedicine

BackgroundSmoking cessation is challenging, despite making use of established smoking cessation therapies. Preclinical studies and one clinical pilot study suggest the antidiabetic drug glucagon-like peptide-1 (GLP-1) analogue to modulate addictive behaviours and nicotine craving. Previously, we reported the short-term results of a randomised, double-blind, placebo-controlled trial. Herein we report long-term abstinence rates and weight developments after 24 and 52 weeks.MethodsThis single-centre, randomised, double-blind, placebo-controlled, parallel group trial was done at the University Hospital Basel in Switzerland. We randomly assigned (1:1) individuals with at least a moderate nicotine dependence willing to quit smoking to either a 12-week treatment with dulaglutide 1.5 mg or placebo subcutaneously once weekly in addition to standard of care smoking cessation therapy (varenicline 2 mg/day and …

BMJ open

IntroductionPeople who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi.Methods and analysisAn open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity …

BackgroundInterpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and preprint servers from Jan 1, 2020, until April 11, 2022, for RCTs of remdesivir in adult patients hospitalised with COVID-19, and contacted the authors of eligible trials to request individual patient data. The primary outcome was all-cause mortality at day 28 after randomisation. We used multivariable hierarchical regression—adjusting for respiratory support, age, and enrollment …

The Lancet

BackgroundHip fracture is the most common injury requiring treatment in hospital. Controversy exists regarding the use of antibiotic loaded bone cement in hip fractures treated with hemiarthroplasty. We aimed to compare the rate of deep surgical site infection in patients receiving high-dose dual-antibiotic loaded cement versus standard care single-antibiotic loaded cement.MethodsWe included people aged 60 years and older with a hip fracture attending 26 UK hospitals in this randomised superiority trial. Participants undergoing cemented hemiarthroplasty were randomly allocated in a 1:1 ratio to either a standard care single-antibiotic loaded cement or high-dose dual-antibiotic loaded cement. Participants and outcome assessors were masked to the treatment allocation. The primary outcome was deep surgical site infection at 90 days post-randomisation as defined by the US Centers for Disease Control and …

Open Forum Infectious Diseases

Background After basic immunization with 2 mRNA SARS-CoV-2 vaccine doses, only a small proportion of patients who are severely immunocompromised generate a sufficient antibody response. Hence, we assessed the additional benefit of a third SARS-CoV-2 vaccine in patients with different levels of immunosuppression. Methods In this observational extension of the COVERALL trial (Corona Vaccine Trial Platform), we recruited patients from the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study (ie, lung and kidney transplant recipients). We collected blood samples before and 8 weeks after the third SARS-CoV-2 vaccination with either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech). The primary outcome was the proportion of participants showing an antibody response (Elecsys Anti-SARS-CoV-2 S test; threshold ≥100 U/mL) 8 weeks after the third …

Trials

BackgroundCigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation.MethodsThis is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment …

The Lancet Rheumatology

Barriers and facilitators to vaccination uptake against COVID-19, influenza, and pneumococcal pneumonia in immunosuppressed adults with immune-mediated inflammatory diseases: A qualitative interview study during the COVID-19 pandemic (2022)

Journal of Clinical Epidemiology

[1] Dal Santo T, Rice DB, Amiri LSN, Tasleem A, Li K, Boruff JT, et al. Methods and results of studies on reporting guideline adherence are poorly reported: a meta-research study. J Clin Epidemiol 2023; 159: 225e34.[2] Chalmers I, Bracken MB, Djulbegovic B, Garttini S, Grant J, G ülmezoglu AM, et al. How to increase value and reduce waste when research priorities are set. Lancet 2014; 383: 156e65.[3] Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet 2009; 374: 86e9.[4] Glasziou P, Altman DG, Bossuyt P, Boutron I, Clarke M, Julious S, et al. Reducing waste from incomplete or unusable reports of biomedical research. Lancet 2014; 383: 267e76.[5] Glasziou P, Chalmers I. Research waste is still a scandaldan essay by Paul Glasziou and Iain Chalmers. BMJ 2018; 363: k4645.[6] Puljak L. Should we expect meta-research studies to be perfectly conducted and …

Open Forum Infectious Diseases

Extension of the COVERALL (COrona VaccinE tRiAL pLatform) randomized trial showed noninferiority in antibody response of the third dose of Moderna mRNA-1273 vaccine (95.3% [95% confidence interval {CI}, 91.9%–98.7%]) compared to Pfizer-BioNTech BNT162b2 vaccine (98.1% [95% CI, 95.9%–100.0%]) in individuals with different levels of immunosuppression (difference, −2.8% [95% CI, −6.8% to 1.3%]).

BMJ Open

Introduction People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi.Methods and analysis An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1: 1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity …

Journal of Clinical Epidemiology

Background and ObjectivesWe investigated the developing methods of reporting guidelines in the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network's database.MethodsIn October 2018, we screened all records and excluded those not describing reporting guidelines from further investigation. Twelve researchers performed duplicate data extraction on bibliometrics, scope, development methods, presentation, and dissemination of all publications. Descriptive statistics were used to summarize the findings.ResultsOf the 405 screened records, 262 described a reporting guidelines development. The number of reporting guidelines increased over the past 3 decades, from 5 in the 1990s and 63 in the 2000s to 157 in the 2010s. Development groups included 2–151 people. Literature appraisal was performed during the development of 56% of the reporting guidelines; 33% used surveys …

BackgroundIn biomedical research, spin is the overinterpretation of findings, and it is a growing concern. To date, the presence of spin has not been evaluated in prognostic model research in oncology, including studies developing and validating models for individualised risk prediction.Study design and settingWe conducted a systematic review, searching MEDLINE and EMBASE for oncology-related studies that developed and validated a prognostic model using machine learning published between 01/01/2019 and 05/09/2019. We used existing spin frameworks and described areas of highly suggestive spin practices.ResultsWe included 62 publications (including 152 developed models; 37 validated models). Reporting was inconsistent between methods and the results in 27% of studies due to additional analysis and selective reporting. Thirty-two studies (out of 36 applicable studies) reported comparisons …

Blood

Background:Patients with CLL have profound immunosuppression, higher mortality rates from COVID-19 infection and poorer responses to vaccination. Patients taking continuous Bruton Tyrosine Kinase inhibitor (BTKi) therapy demonstrate the poorest responses to vaccination, despite booster COVID-19 doses. BTKi therapy is taken continuously and is non-selective, inhibiting B cell receptor signalling in healthy B cells, as well as CLL cells. As covalent BTKi therapies have a short half-life and BTK receptor occupancy increases on stopping drug, a temporary pause in BTKi around the time of vaccination may improve immunity.Aim:To assess whether a temporary three-week pause of daily BTKi treatment around COVID-19 vaccination improves the immune response in people with Chronic Lymphocytic Leukaemia (CLL) whilst maintaining disease control.Methods: Patients with CLL in CR/stable PR taking either …

Topics in Antiviral Medicine

Background:The interpretation of the evidence from randomized clinical trials (RCTs) on remdesivir for hospitalized patients with coronavirus disease 2019 (COVID-19) is conflicting. We conducted a systematic review and individual patient data meta-analysis (IPDMA) of RCTs to assess the benefit and harm of remdesivir compared to placebo or usual care in hospitalized patients and whether treatment effects differed between prespecified subgroups. Method (s) We systematically searched electronic databases and registries through April 11th 2022 and contacted authors of eligible trials to share individual patient data. The primary outcome was all-cause mortality at day 28. We used multivariable hierarchical regression adjusting for respiratory support, age, and enrollment period to investigate effect modifiers. The study was registered in PROSPERO (CRD42021257134). Result (s) Out of nine eligible RCTs, eight provided individual data for 10480 hospitalized COVID-19 patients (99% of global IPD) recruited between February 2020 and April 2021. Within 28 days of randomization, 662 of 5317 patients (12.5%) assigned to remdesivir and 706 of 5005 (14.1%) assigned to no remdesivir died (adjusted odds ratio [aOR] 0.88; 95% confidence interval [CI], 0.78-1.00; p= 0.045). We found evidence for a credible subgroup effect according to respiratory support at baseline (interaction p= 0.019). Of those ventilated including high-flow oxygen, 253/844 (30.0%) assigned to remdesivir died versus 241/846 (28.5%) assigned to no remdesivir (aOR 1.10 [0.88-1.38]; low certainty evidence). Of those receiving no or low flow oxygen, 409/4473 (9.1%) assigned …

JAMA Network Open

ImportanceNumerous studies have shown that adherence to reporting guidelines is suboptimal.ObjectiveTo evaluate whether asking peer reviewers to check if specific reporting guideline items were adequately reported would improve adherence to reporting guidelines in published articles.Design, Setting, and ParticipantsTwo parallel-group, superiority randomized trials were performed using manuscripts submitted to 7 biomedical journals (5 from theBMJPublishing Group and 2 from the Public Library of Science) as the unit of randomization, with peer reviewers allocated to the intervention or control group.InterventionsThe first trial (CONSORT-PR) focused on manuscripts that presented randomized clinical trial (RCT) results and reported following the Consolidated Standards of Reporting Trials (CONSORT) guideline, and the second trial (SPIRIT-PR) focused on manuscripts that presented RCT protocols and …

Trials

Background Benefits to patients from reduced depression have been shown from monitoring progress with patient-reported outcome measures (PROMs) in psychological therapy and mental health settings. This approach has not yet been researched in the United Kingdom for primary care, which is where most people with depression are treated in the United Kingdom. Methods This is a parallel-group cluster randomised trial with 1:1 allocation to intervention and control. Patients who are age 18+ years, with a new episode of depressive disorder/symptoms, meet the inclusion criteria. Patients with current depression treatment, comorbid dementia/psychosis/substance misuse/suicidal ideas are excluded. The intervention includes the Administration of Patient Health Questionnaire (PHQ-9) as a PROM within 2 weeks of diagnosis and at follow-up 4 weeks later. General practitioners are trained in interpreting scores …

Trials

BackgroundKeloid is a skin disorder that results from excessive fibrous tissue growth in the area of the initial trauma. Treating keloids can be challenging since the success of various treatments varies from one study to another. Triamcinolone acetonide injection, a standard treatment, can cause undesirable side effects. Meanwhile, the effectiveness of existing topical therapies for keloids is not always reliable. The pro-inflammatory, pro-proliferative, and pro-fibrotic effects of angiotensin II in human skin contribute to keloid formation. Losartan potassium, an angiotensin II blocker, has the potential to act as an anti-keloid agent. Due to the thicker skin structure of a keloid and ease of application, ethosome gel is chosen as a safe and comfortable carrier for losartan potassium, making it a good choice for treating keloids.MethodsIn this randomised clinical trial, 46 adults with keloids were divided into two treatment groups …

Trials

ObjectivesEstablishment of effective evidence-based interventions in rehabilitation of working memory (WM) deficits after acquired brain injury (ABI) is sorely needed. Despite robust evidence for the efficiency of clinical hypnosis in a wide range of clinical conditions, and improved understanding of mechanisms underlying its effects, the potential of clinical hypnosis in cognitive rehabilitation is underexplored. A recent study has shown large effects of hypnotic suggestion on WM capacity following ABI. This randomized controlled trial aims to evaluate and explore the replicability of these findings and examine the generalization of treatment effects. The study will also explore possible mechanisms of change.MethodsNinety patients will be recruited from the Sunnaas Rehabilitation Hospital. Inclusion criteria are nonprogressive ABI, minimum 12-month post-injury, ongoing WM deficits, and age between 18 and 67 years …

Trials

BackgroundCystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins.MethodsThis prospective, single-blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble …

Trials

BackgroundApproximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs).MethodsWe will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom …

Trials

BackgroundApproximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs).MethodsWe will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom …

Trials

BackgroundDespite the critical importance of clinical trials to provide evidence about the effects of intervention for children and youth, a paucity of published high-quality pediatric clinical trials persists. Sub-optimal reporting of key trial elements necessary to critically appraise and synthesize findings is prevalent. To harmonize and provide guidance for reporting in pediatric controlled clinical trial protocols and reports, reporting guideline extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines specific to pediatrics are being developed: SPIRIT-Children (SPIRIT-C) and CONSORT-Children (CONSORT-C).MethodsThe development of SPIRIT-C/CONSORT-C will be informed by the Enhancing the Quality and Transparency of Health Research Quality (EQUATOR) method for reporting guideline development in …

Trials

BackgroundIndigenous youth in Northwestern Ontario who need mental health supports experience longer waits than non-Indigenous youth within the region and when compared to youth in urban areas. Limited access and extended waits can exacerbate symptoms, prolong distress, and increase risk for adverse outcomes. Innovative approaches are urgently needed to provide support for Indigenous youth in Northwestern Ontario. Using a randomized controlled trial design, the primary objective of this study is to determine the effectiveness of the JoyPop app compared to usual practice (UP; monitoring) in improving emotion regulation among Indigenous youth (12–17 years) who are awaiting mental health services. The secondary objectives are to (1) assess change in mental health difficulties and treatment readiness between youth in each condition to better understand the app’s broader impact as a waitlist tool …

Trials

Background Benefits to patients from reduced depression have been shown from monitoring progress with patient-reported outcome measures (PROMs) in psychological therapy and mental health settings. This approach has not yet been researched in the United Kingdom for primary care, which is where most people with depression are treated in the United Kingdom. Methods This is a parallel-group cluster randomised trial with 1:1 allocation to intervention and control. Patients who are age 18+ years, with a new episode of depressive disorder/symptoms, meet the inclusion criteria. Patients with current depression treatment, comorbid dementia/psychosis/substance misuse/suicidal ideas are excluded. The intervention includes the Administration of Patient Health Questionnaire (PHQ-9) as a PROM within 2 weeks of diagnosis and at follow-up 4 weeks later. General practitioners are trained in interpreting scores …

Trials

Correction: Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome — a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III) - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now. Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Trials v.25; 2024 PMC10941458 Other Formats PDF (623K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Trials v.25; 2024 PMC10941458 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply …

Trials

BackgroundAdolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the ‘Building Resilience through Socioemotional Training’ (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology.MethodsA cluster randomised allocation design is adopted with randomisation at the school year …

Trials

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.MethodsThe HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is …

Trials

BackgroundThe World Health Organization recommends universal iron supplementation for children aged 6–23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation.MethodsThis will be a two-arm, randomised controlled trial. Gambian children aged 6–12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 …

Trials

BackgroundLiver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD).Methods/designThe BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis …

Trials

In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and …

Trials

BackgroundOccupational Therapists use craft-making activities as therapeutic interventions to improve physical and psychological functioning of injured people. Despite the therapeutic effects, craft-making is not routinely used in hand rehabilitation as an intervention for patients with upper limb fractures. These patients often experience physical and psychosocial issues; however, without supportive evidence, therapists hesitate to integrate craft-making into upper limb rehabilitation.PurposeThis study aims to determine the effect of a conventional therapy combined with therapeutic craft-making on disability, post-traumatic stress, and physical performance in patients with lower-third forearm fractures.MethodsPriori analysis determined that 38 patients will be needed for this superiority randomized controlled trial to be conducted in a hand and upper limb rehabilitation center. Eligible participants must comprehend …

Trials

BackgroundOver 3000 young people under the age of 18 are admitted to Tier 4 Child and Adolescent Mental Health Services (CAMHS) inpatient units across the UK each year. The average length of hospital stay for young people across all psychiatric units in the UK is 120 days. Research is needed to identify the most effective and efficient ways to care for young people (YP) with psychiatric emergencies. This study aims to evaluate the clinical effectiveness and cost-effectiveness of intensive community care service (ICCS) compared to treatment as usual (TAU) for young people with psychiatric emergencies.MethodsThis is a multicentre two-arm randomized controlled trial (RCT) with an internal pilot phase. Young people aged 12 to < 18 considered for admission at participating NHS organizations across the UK will be randomized 1:1 to either TAU or ICCS. The primary outcome is the time to return to or start …

Trials

Digital interventions offer many possibilities for improving health, as remote interventions can enhance reach and access to underserved groups of society. However, research evaluating digital health interventions demonstrates that such technologies do not equally benefit all and that some in fact seem to reinforce a “digital health divide.” By better understanding these potential pitfalls, we may contribute to narrowing the digital divide in health promotion. The aim of this article is to highlight and reflect upon study design decisions that might unintentionally enhance inequities across key research stages—recruitment, enrollment, engagement, efficacy/effectiveness, and retention. To address the concerns highlighted, we propose strategies including (1) the standard definition of “effectiveness” should be revised to include a measure of inclusivity; (2) studies should report a broad range of potential inequity indicators of …

Trials

BackgroundWithin England, children and young people (CYP) who come into police custody are referred to Liaison and Diversion (L&D) teams. L&D teams have responsibility for liaising with healthcare and other support services while working to divert CYP away from the criminal justice system but have traditionally not provided targeted psychological interventions to CYP. Considering evidence that Solution Focused Brief Therapy (SFBT) leads to a reduction in internalising and externalising behaviour problems in CYP, the aim of this randomised controlled trial (RCT) was to determine whether there is a difference between services as usual (SAU) plus SFBT offered by trained therapists working within a L&D team, and SAU alone, in reducing offending behaviours in 10–17-year-olds presenting at police custody.MethodsDesign: two-arm individually RCT with internal pilot and process evaluation.Participants: N …

Trials

BackgroundDepression continues to be an ongoing threat to adolescent well-being with Black adolescents being particularly vulnerable to greater burdens of depression as well as lower mental health service utilization. Black adolescents are likely to have untreated depression due to social network influences, varied perceptions of services and providers, or self-stigma associated with experiencing depressive symptoms. Furthermore, if or when treatment is initiated, low engagement and early termination are common. To address this gap, a trial is being conducted to preliminarily test the effectiveness of an engagement intervention targeting Black adolescents with depression in school mental health services in New York City.MethodsA total of 60 Black middle and high school adolescents displaying depressive symptoms are equally randomized (based on school site) to the treatment arms. Both trial arms deliver …