Trials[JOURNAL]
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Early intensive antihypertensive treatment in high-risk population of intracerebral haemorrhage expansion identified by artificial intelligence (ARCHES): study protocol for a multicentre randomised controlled trial.
Wu L, Shan S, Kang K … +8 more , Ye W, Meng X, Li H, Xu Q, Wang A, Li Z, Zhao X, Li N
Trials · 2026 Jun · PMID 42286617 · Full text
BACKGROUNDS: Haematoma expansion (HE) is a significant factor in poor outcomes following intracerebral haemorrhage (ICH). Studies have suggested that acute intensive antihypertensive treatment could reduce HE. However, t...
BACKGROUNDS: Haematoma expansion (HE) is a significant factor in poor outcomes following intracerebral haemorrhage (ICH). Studies have suggested that acute intensive antihypertensive treatment could reduce HE. However, the impact of early intensive blood pressure reduction on patients with ICH at high risk of HE remains unclear. Therefore, screening ICH patients for high risk of HE upon admission and initiating early intensive blood pressure reduction could improve their prognosis. In this study we utilise a five-point scoring system integrating a deep learning system based on non-contrast CT imaging and clinical predictors to identify ICH patients at high risk of HE. This study aims to compare the efficacy, safety, and feasibility of early intensive antihypertensive treatment versus standard antihypertensive treatment for patients identified as being at high risk of HE. METHODS: The early intensive antihypertensive treatment in high-risk population of intracerebral haemorrhage expansion predicted by artificial intelligence (ARCHES), is a multicentre, prospective, randomised, open-label, blinded-endpoints clinical trial that will include an estimated 680 participants. ICH patients within 6 h of symptom onset, and at high risk of haematoma expansion with ≥ 3 points on the artificial intelligence-based haematoma expansion 5-point prediction score, will be randomly assigned to receive either intensive antihypertensive treatment (targeting systolic blood pressure control between 130 and 140 mmHg within the first hour of treatment, and maintaining this level for 7 days) or standard antihypertensive treatment (targeting systolic blood pressure control between 140 and 180 mmHg, and maintaining for 7 days). The primary outcome is death or severe disability at 90 days. DISCUSSION: The ARCHES study aims to verify the hypothesis that early intensive blood pressure lowering leads to reduced HE and improved functional outcomes with good safety in ICH patients at high risk of HE. TRIAL REGISTRATION: This study was registered at the Clinical Trials under registry number NCT06242938. Registered on Feb 2, 2024. https://clinicaltrials.gov/study/NCT06242938.
Remimazolam besylate reduces hypoxemia during painless gastrointestinal endoscopy in elderly patients: study protocol for a multicenter, randomized, controlled trial.
Zhang FY, Ma Z, Zhang W … +2 more , Gao ZF, An LX
Trials · 2026 Jun · PMID 42277954 · Full text
BACKGROUND: Hypoxemia and circulatory depression are common complications in elderly patients undergoing procedure sedation anesthesia (PSA) for gastrointestinal (GI) endoscopy. Remimazolam besylate, a novel ultra-short-...
BACKGROUND: Hypoxemia and circulatory depression are common complications in elderly patients undergoing procedure sedation anesthesia (PSA) for gastrointestinal (GI) endoscopy. Remimazolam besylate, a novel ultra-short-acting benzodiazepine, is postulated to offer a superior safety profile with reduced respiratory depressant effects compared to propofol. This study aims to compare the incidence of hypoxemia of remimazolam besylate versus propofol for painless GI endoscopy in elderly patients through a multicenter randomized controlled trial. METHODS: This study is a multicenter, double-blind, parallel, randomized, controlled trial. Six hundred seventy elderly patients scheduled for GI endoscopy under PSA are enrolled at three medical institutions in China from 2025 to 2027. Patients will be randomized 1:1 to receive remimazolam besylate (0.15 mg/kg) plus sufentanil vs propofol (1.5 mg/kg) plus sufentanil, stratified by age (65-70 vs.70-75 years old) and 3 research institution. The primary outcome is the incidence of intraoperative hypoxemia, defined as any event where peripheral oxygen saturation (SpO₂) is ≥ 75% and < 90%, lasting for less than 60 s. Secondary outcomes include hypoxemia degree, emergency airway management, propofol consumption, hemodynamic stability, involuntary body movements, procedure/recovery times, and clinician satisfaction. DISCUSSION: This trial evaluates whether remimazolam besylate reduces respiratory depression and improves safety profiles in elderly patients during painless GI endoscopy. It may provide evidence for optimizing sedation strategies in high-risk elderly populations. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2500110081, registrated on September 30, 2025.
Translation and interpreting services must be considered across the lifecycle of clinical trials.
Roberts K, Lewis R, Iqbal G … +2 more , Rick C, Shepherd V
Trials · 2026 Jun · PMID 42277920 · Full text
BACKGROUND: Inclusive clinical research requires that all prospective participants are provided with accessible, comprehensible information to support informed decision-making regarding trial participation. However, peop...
BACKGROUND: Inclusive clinical research requires that all prospective participants are provided with accessible, comprehensible information to support informed decision-making regarding trial participation. However, people with limited English proficiency (LEP) remain disproportionately excluded from trials in English-speaking countries, largely due to insufficient translation and interpretation support. This exclusion compromises equity, participant safety, and the integrity and generalisability of trial findings. MAIN BODY: This commentary highlights why language support must be considered across the entire clinical trial lifecycle, rather than limited to recruitment and consent stages. We examine challenges including identifying which languages and materials require translation; quality assurance of translations; budgeting complexities; reliance on underqualified interpreters; and variability in provision across sites. Practical implications span recruitment, informed consent, outcome measures, intervention delivery, monitoring recruitment and retention, safety reporting, and communication to participants throughout the trial. We emphasise the need for early planning, transparent budgeting, robust quality standards, and researcher training. Drawing on existing frameworks and recent evidence, we provide recommendations on how sponsors, funders, healthcare providers, research teams, and research governance organisations can move towards more systematic and equitable approaches to translation and interpretation. CONCLUSION: Addressing linguistic diversity in clinical trials requires a coordinated, lifecycle-wide strategy that goes beyond providing translated materials at the recruitment consultation. System-level changes, such as clear national standards, centralised models of provision, and better training are essential to reduce inequities and enhance the reliability of trial outcomes. Ensuring that people with LEP are supported throughout their participation will strengthen trust, improve safety, and contribute to more representative evidence for healthcare decision-making.
Effects of an app-augmented cognitive behavioral therapy using the Journaling App for Youth (JAY) for adolescents with internalizing disorders-a study protocol.
Görtz-Dorten A, Schindler L, Klee J … +2 more , Wähnke L, Döpfner M
Trials · 2026 Jun · PMID 42277911 · Full text
BACKGROUND: Internalizing disorders such as anxiety and depression can be especially severe during adolescence, presenting significant challenges for affected individuals. While cognitive-behavioural therapy (CBT) has sh...
BACKGROUND: Internalizing disorders such as anxiety and depression can be especially severe during adolescence, presenting significant challenges for affected individuals. While cognitive-behavioural therapy (CBT) has shown promise as an effective treatment for these conditions, a significant proportion of youth do not benefit sufficiently from CBT. One critical factor that may influence the effectiveness of CBT is adherence to therapy homework, with evidence suggesting a relationship between homework completion and therapy outcomes, including symptom reduction. In this context, smartphone apps have emerged as a potentially helpful tool to enhance adherence by providing engaging ways for adolescents to complete their therapy homework. However, in Germany, there is currently a lack of evaluated smartphone apps that can be deployed as adjuncts to CBT for adolescents. METHOD: This study is designed as a randomized controlled trial (RCT). It will evaluate the effects of the JAY smartphone app on therapy homework adherence during CBT for adolescents with internalizing disorders (n = 35) compared to CBT with standard paper-and-pencil homework (n = 35). DISCUSSION: The findings of the JAY trial may contribute to the understanding of how smartphone apps can be integrated into CBT for adolescents to enhance therapy homework adherence and ultimately treatment outcomes. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00026623. Registered on 13th October 2023, https://drks.de/search/de/trial/DRKS00026623/details .
From pilot to region-wide impact: study protocol for an implementation study and randomised controlled trial of the LEX LOTSEN OWL Care and Case Management System.
Arnold M, Gscheidle S, Lange S … +13 more , Haring M, Stegmeier E, Klampfleitner H, Kurscheid C, Schluttig M, Borchers U, Stampa S, Schnecke JH, von Schell A, Pries R, Miethe J, Galle G, Brinkmeier M
Trials · 2026 Jun · PMID 42277904 · Full text
BACKGROUND: Care and case management (CCM) is considered a promising approach to bridging gaps in cross-sectoral coordination for high-need patients, aiming to improve access, continuity, and overall care experiences. De...
BACKGROUND: Care and case management (CCM) is considered a promising approach to bridging gaps in cross-sectoral coordination for high-need patients, aiming to improve access, continuity, and overall care experiences. Despite promising pilot initiatives, comprehensive models that investigate both the "how" (implementation and sustainable scaling) and the "what" (patient outcomes) are lacking. To address this gap, the "LEX LOTSEN OWL" (LLO) project (registered under DRKS00034188) employs a hybrid study design, combining implementation research with a classic randomized controlled trial (RCT) across seven districts in the German East Westphalia-Lippe (Ostwestfalen-Lippe, OWL) region. By examining governance structures and organizational frameworks, LLO seeks to provide insights into the broader applicability and feasibility of CCM programs. METHODS/DESIGN: This study encompasses two interlinked components: (1) Implementation research via a process evaluation framework accompanying the establishment of "CCM offices" (Lotsenbüros) in seven districts, introduced in a staggered manner. Qualitative and quantitative methods (including interviews, document analysis, and process metrics) will be applied to identify facilitating factors and barriers, guided by a governance framework and rapid ethnographic assessments. (2) Outcome research via RCT at the patient level. Adults with complex care needs will be randomized into a care and case management group or a control group receiving usual care. The primary endpoints are relational coordination (system level), which is assessed via the Gittell Relational Coordination Questionnaire, and experienced quality of care (Patient Experience of Integrated Care Scale, PEICS). The secondary endpoints include (re)hospitalization, mortality, health-related quality of life, patient self-management, and caregiver self-efficacy, allowing a comprehensive assessment of clinical and patient-centered outcomes. DISCUSSION: This dual design aims to generate evidence of both structural and process-related factors influencing implementation while evaluating the potential clinical effectiveness of CCM. The results may inform how an indication-independent CCM can be seamlessly integrated into diverse healthcare settings. By providing insights into governance, organizational strategies, and patient-specific benefits, LLO may inform future policy and practice, foster improved coordination, enhance continuity, and increase patient engagement in routine health systems. Additionally, the project explores scalability factors critical for decision-makers. Collectively, this initiative has the potential to contribute to the development of sustainable, patient-centered care models. TRIAL REGISTRATION: This study is prospectively registered in the German Clinical Trials Register (DRKS, DRKS00034188 ) on 17 May 2024.
Healthcare professionals' perspectives on the barriers and enablers of cancer clinical trial participation among Arabic-speaking cancer patients in Australia: a qualitative study.
Saleh Moussa R, Edwards LM, Camit M … +31 more , Jeyachandran C, Luckett T, Smith B, Brady B, Kochovska S, Bejjani C, Gonzalez M, El-Kabbout N, Abousamra A, Gadalla A, Zakhary I, Matti A, Kattan R, Wu V, Chua W, Wong K, Subramaniam S, McErlean G, Sidhu B, Jennings M, Avery S, Karikios D, Boyle F, Trad W, Ng W, Della-Fiorentina S, Hong M, Nindra U, Fielding S, Agar M, Pal A
Trials · 2026 Jun · PMID 42277890 · Full text
BACKGROUND: Culturally and ethnically diverse communities are underrepresented in cancer clinical trials, further contributing to existing health inequities. Research often overlooks how upstream social determinants of h...
BACKGROUND: Culturally and ethnically diverse communities are underrepresented in cancer clinical trials, further contributing to existing health inequities. Research often overlooks how upstream social determinants of health (SDOH) might contribute to these inequities, instead focusing on individual-level barriers. Arabic is the third most spoken language in Australia and is the focus of this study. This study aims to explore how upstream SDOH influence clinical trial participation among Arabic-speaking cancer patients (ASCPs), as perceived by healthcare professionals (HCPs). METHODS: A qualitative study comprising virtual focus groups with HCPs with experience recruiting ASCPs into clinical trials. Participants were recruited via professional networks and social media using snowball sampling. The Sociocultural Framework for Health Service Disparities was used to identify perceived barriers and enablers to cancer clinical trial participation relating to structural, healthcare provider, and environmental factors. Focus groups were analysed using the Best Fit approach by two independent coders. RESULTS: Fourteen participants were recruited (ten medical specialists, two nurses, one clinical trial coordinator and one researcher). Structural and healthcare provider barriers centred on English-language proficiency. Structural barriers included limited consultation time, restrictive trial eligibility criteria, lack of translated study materials, and a lack of workforce diversity. Language discourse reduced HCPs' confidence in patient understanding of trial information and consequently the informed consent procedure. By advocating for translated materials, booking longer consults, and engaging interpreters, HCPs became enablers to trial participation. Family support networks were identified as environmental enablers by facilitating trial-related conversations; however, they also acted as barriers by compromising patient autonomy in decision-making. Perceived scepticism and distress emerged as environmental barriers that shaped attitudes toward cancer diagnosis and trial participation. CONCLUSION: Findings highlight how upstream SDOH can create barriers to cancer clinical trial access, thereby reducing opportunities for participation among ASCPs in Australia. Although the barriers were described in terms of language, they may reflect a broader lack of cultural competency. Further research into strategies integrating enablers such as time, workforce diversity, interpreter engagement and translated resources is essential to inform inclusive healthcare systems and research design, with potential implications beyond the Arabic-speaking community. TRIAL REGISTRATION: Ethical approval for this study was granted by the University of Technology Sydney Human Research Ethics Committee (ETH21-6506, 14/01/2022).
Incremental value of non-pharmacokinetic adherence measures for dapivirine vaginal ring use in resource limited setting.
Abaasa AM, Kusemererwa S
Trials · 2026 Jun · PMID 42277878 · Full text
BACKGROUND: Measuring product use adherence remains a challenge in HIV prevention trials and routine care setting. We determined agreement among and between non-pharmacokinetic (non-PK) and pharmacokinetic (PK) adherence...
BACKGROUND: Measuring product use adherence remains a challenge in HIV prevention trials and routine care setting. We determined agreement among and between non-pharmacokinetic (non-PK) and pharmacokinetic (PK) adherence measures, and also assessed the incremental value of each measure among women using the dapivirine vaginal ring (DVR) in the Ring trial in southwestern Uganda. METHODS: Between 2013 and 2016, the International Partnership for Microbicides conducted the Ring trial in which women were randomised to dapivirine or placebo vaginal ring in a ratio of 2:1. A total of 197 women were randomised. Four adherence measures were used, including PK: (i) testing of the dapivirine residual levels in used rings and (ii) plasma drug concentrations; non-PK: (iii) self-reported and (iv) ring colour change, all measured every 4 weeks for 2 years. We defined product use adherence as having the expected dapivirine residual levels (≤ 23.5 mg of 25 mg) or plasma concentration (≥ 95 pg/mL) or having used the ring as instructed at ≥ 80% of the visits completed. We used dapivirine residual levels as a gold standard and measured agreement and incremental value of other measures in predicting residual adherence using Cohen's kappa statistic, a discriminant C-statistic and Receiver Operating Characteristic (ROC) curve, stratified by age < 25 or ≥ 25 years. RESULTS: Of the 197 women randomised, 66% were aged ≥ 25 years and in both age groups, > 80% completed 2 years of follow-up. In women aged < 25 years, percent agreement between non-PK measures and that between non-PK and PK measures was moderate 57.8% to 66.7%. While that between PK measures was high 86.7%. In the women aged ≥ 25 years, agreements between combinations of measures were 80.5% to 86.2%. The incremental value of non-PK measures was poor in women aged < 25 years, AROC = 0.62, and good in those age 25 + years, area under receiver operating curve (AROC) = 0.77. CONCLUSION: Combining non-PK measures to measure dapivirine residual level adherence in women aged ≥ 25 years could be useful in DVR use, in the context of resource-scarce settings. However, this is of limited value in young women aged < 25 years. TRIAL REGISTRATION: Reg No. NCT01539226. Registered on February 24, 2012.
Supplemental Oxygen Strategies in children with BronchoPulmonary Dysplasia (the SOS BPD study): statistical analysis plan for a multicenter randomized controlled trial.
de Ridder R, Merkus MP, Vrijlandt EJLE … +5 more , Reiss IKM, van Kaam AH, Pijnenburg MW, Onland W, SOS BPD study group
Trials · 2026 Jun · PMID 42277858 · Full text
BACKGROUND: Supplemental oxygen remains the primary treatment for preterm infants with established bronchopulmonary dysplasia (BPD). Although randomized controlled trials have evaluated lower versus higher oxygen saturat...
BACKGROUND: Supplemental oxygen remains the primary treatment for preterm infants with established bronchopulmonary dysplasia (BPD). Although randomized controlled trials have evaluated lower versus higher oxygen saturation targets in preterm infants before 36 weeks postmenstrual age, evidence beyond this age is lacking. The aim of the Supplemental Oxygen Strategies in children with BronchoPulmonary Dysplasia (SOS BPD) study is to evaluate the effect of a higher oxygen saturation lower limit of 95%, compared with a lower limit of 90%, on lung growth by proxy of weight standard deviation score (SDS), at 6 months corrected age in infants with established BPD. This document outlines the statistical analysis plan for the SOS-BPD study. METHODS/DESIGN: The SOS BPD study is a multicenter, pragmatic, non-blinded, randomized trial in preterm infants with moderate or severe BPD. Eligible infants are randomized between 36 and 38 weeks postmenstrual age to a lower oxygen saturation limit of 95% or 90%, after parental informed consent. The assigned oxygen saturation lower limit is maintained until respiratory support can be discontinued. The primary outcome is weight SDS at 6 months corrected age. Secondary outcomes include anthropometrics measured at 6 and 12 months corrected age, rehospitalizations for respiratory reasons and respiratory complaints. This statistical analysis plan is written and submitted without knowledge of the data. TRIAL REGISTRATION: Overview of Medical Research in the Netherlands (OMON), NL-OMON54694. Registered on 09-08-2018, URL: https://onderzoekmetmensen.nl/en/trial/54694.
Effect of autonomous motivation support on obesity prevention in early adolescents: a study protocol of cluster-randomized controlled trial based on the integrated SDT-TPB framework.
Kong JQ, Chen J, Yang Y … +6 more , Yang YH, Liu JY, Hu RZ, Li JY, Zhang XR, Liu Z
Trials · 2026 Jun · PMID 42277851 · Full text
BACKGROUND: The prevalence of obesity among early adolescents continues to rise, yet most existing interventions demonstrate only short-term efficacy. Children in early adolescence have increasingly strong autonomy, and...
BACKGROUND: The prevalence of obesity among early adolescents continues to rise, yet most existing interventions demonstrate only short-term efficacy. Children in early adolescence have increasingly strong autonomy, and enhancing their autonomous motivation holds promise for the long-term maintenance of healthy behavior, and further research is urgently needed. METHODS: Based on an integral framework of Self-Determination Theory and Theory of Planned Behavior (SDT-TPB), this project will conduct a cluster-randomized controlled trial. This trial will compare an autonomous motivation support group against a control group, with four follow-up assessments over 2 years. We will examine between-group differences in autonomous motivation, health behaviors, and adiposity outcomes to evaluate the intervention's immediate and long-term maintenance effects. Unlike previous approaches that focused primarily on behaviors, this study specifically targets the motivational drivers of behavior change. DISCUSSION: Considering the developmental characteristic of early adolescents and theoretical framework of SDT and TPB, this school-based cluster-randomized controlled trial is expected to elucidate the complete pathway from motivation to behavioral change. We anticipate that the findings will help overcome a key bottleneck in pediatric obesity interventions and advance strategies for chronic disease prevention and control. TRIAL REGISTRATION: ICH GCP NCT06547567. Registered on 7 August 2024.
Efficacy and safety of SarogLItazar as an add-on medication to Metformin and lifestyle intervention in women with PolyCystic Ovary Syndrome (SLIM-PCOS trial): study protocol for a randomized, open-label, parallel group clinical trial.
Mittal N, Singhal S, Mittal R
Trials · 2026 Jun · PMID 42271514 · Full text
BACKGROUND: Emerging concepts on the role of insulin resistance (IR) in the pathogenesis of polycystic ovary syndrome (PCOS) have driven a shift in the therapeutic approach towards interventions targeting IR. SarogLItaza...
BACKGROUND: Emerging concepts on the role of insulin resistance (IR) in the pathogenesis of polycystic ovary syndrome (PCOS) have driven a shift in the therapeutic approach towards interventions targeting IR. SarogLItazar as an add-on to Metformin in PolyCystic Ovary Syndrome (SLIM-PCOS) trial aims to test the efficacy and safety of saroglitazar, a dual peroxisome proliferator-activated receptor (PPAR α/γ) agonist belonging to "glitazar" class of drugs, on top of metformin and lifestyle intervention in PCOS. METHODS: SLIM-PCOS is an investigator-initiated, randomized, open label, parallel group, superiority, clinical trial. Around 140 PCOS patients will be randomized in 1:1 ratio to either of the two study groups: Group A: tablet saroglitazar (4 mg daily) + tablet metformin (500 mg twice daily) + lifestyle intervention; and Group B: tablet metformin + lifestyle intervention. Lifestyle intervention will comprise of dietary intervention and physical activity. Treatment will be given for 24 weeks and post-treatment follow up done at 36 weeks. The primary outcome is to compare the change in serum sex hormone binding globulin (SHBG) levels at 24 weeks from baseline between the two groups. Secondary efficacy outcomes include clinical (anthropometry, hirsutism, menstrual cycles); metabolic and gonadal parameters (lipid profile, IR, ovarian hormones and androgens, metabolic syndrome); hepatic steatosis on transabdominal scan and quality of life. Safety outcomes include patient reported adverse events, hematological and biochemical safety parameters. Data will be analysed as per intention to treat (ITT) principle using validated statistical software. Two-tailed P-value < 0.05 will be considered statistically significant. DISCUSSION: SLIM-PCOS trial will provide evidence on the potential therapeutic application of saroglitazar in PCOS. Based on the study outcomes and the drug's mechanism of action, future studies may be planned to investigate into the role of this novel glitazar in PCOS patients having diabetes, dyslipidemia, non-alcoholic fatty liver disease and other associated co-morbidities. TRIAL REGISTRATION: Prospectively registered with the Clinical Trials Registry of India (Trial ID: CTRI/2025/09/094653); registered September 12, 2025. https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=142027&EncHid=25944.27666&modid=1&compid=19.
Retraction Note: Effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia: protocol for a randomized, double-blind, controlled study.
Tao W, Xie Y, Ding W … +3 more , Bao J, Zhang Y, Hu X
Trials · 2026 Jun · PMID 42265726 · Full text
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Blinding outcome assessors in randomised controlled trials of psychological interventions: how is it done? A narrative review.
O'Keeffe S
Trials · 2026 Jun · PMID 42265712 · Full text
BACKGROUND: Blinding of patients, clinicians and outcome assessors is a key measure for minimising bias in randomised controlled trials (RCTs). In trials of psychological interventions, where outcome measures often use s...
BACKGROUND: Blinding of patients, clinicians and outcome assessors is a key measure for minimising bias in randomised controlled trials (RCTs). In trials of psychological interventions, where outcome measures often use subjective measures, the blinding of outcome assessors is particularly important. However, there are few guidelines on how blinding of outcome assessors can be achieved in practice. The aim of this study was to identify procedures used for blinding outcome assessors in RCTs of psychological interventions. METHODS: A narrative review was conducted through a PubMed database search covering the period from January 2023 to December 2024, restricted to studies published in the six highest impact factor journals in the field of psychiatry and mental health. Studies were included if they were (1) an RCT and (2) focused on psychological intervention(s). Descriptive statistics were used to summarise the study characteristics, and content analysis of the published reports was conducted to describe the methods used to maintain blinding of outcome assessors. RESULTS: Fifty-two eligible studies were identified which reported on RCTs of psychological interventions. Of those, the majority reported that outcome assessors were blinded to participants' treatment allocation (n = 44, 85%). Of the studies with blinded outcome assessors, 27 reported information on the procedures used to maintain blinding (61%). Methods for maintaining blinding were avoiding unblinding by participants (n = 16), tracking and assessing blinding efficacy (n = 12), replacing unblinded assessors (n = 11), managing communication within the team (n = 9), clear designation of blind and unblind staff roles (n = 8) and management of records (n = 6). The majority of studies reported a single method for maintaining blinding of outcome assessors. CONCLUSION: While the majority of RCTs of psychological interventions reported that outcome assessors were blind to participants' treatment allocation, there was often no or minimal information about procedures used to maintain blinding. A limitation of this study is that it was restricted to RCTs reported in high-impact journals so it does not provide a comprehensive review of all relevant studies. Maintaining blinding of outcome assessors requires substantial planning and efforts throughout the conduct of an RCT and this should be reported so that conclusions drawn from RCTs can be made with confidence.
Evaluating intramuscular epinephrine in pediatric out-of-hospital cardiac arrest (the PRIME trial): study protocol for a multi-centre, stepped-wedge cluster quasi-randomized controlled trial.
Idrees S, Assaf M, Davis M … +4 more , Garcia-Bournissen F, Loosley J, Miller MR, Tijssen JA
Trials · 2026 Jun · PMID 42260675 · Full text
BACKGROUND: Pediatric out-of-hospital cardiac arrest (POHCA) is a time-sensitive event with a high mortality rate. Epinephrine is a key first-line medication used during cardiac arrest resuscitation to support perfusion...
BACKGROUND: Pediatric out-of-hospital cardiac arrest (POHCA) is a time-sensitive event with a high mortality rate. Epinephrine is a key first-line medication used during cardiac arrest resuscitation to support perfusion and return of spontaneous circulation (ROSC). Guidelines for the management of POHCA recommend paramedics administer epinephrine as soon as possible by intravenous (IV) or intraosseous (IO) injection. However, successfully inserting an IV or IO line can be challenging in high-stress situations, particularly in a poorly perfused, small child. In contrast, intramuscular (IM) epinephrine, which is the standard of care in anaphylaxis management, does not require paramedics to secure vascular access and may lead to a shorter time to first dose. The POHCA Resuscitation: Evaluation of IM Epinephrine (PRIME) trial aims to evaluate the impact of IM epinephrine on POHCA outcomes. The primary objective of the PRIME trial is to determine if an initial dose of IM epinephrine improves time to return of spontaneous circulation (ROSC) compared to standard of care alone. METHODS: The PRIME trial is a prospective, multi-centre, pragmatic, two-arm, open-label, stepped-wedge cluster quasi-randomized controlled trial. We will randomize at the level of the paramedic service, as individual-level randomization is not possible due to the inclusion of multiple, heterogeneous regions. Each site will serve as its own control. This study is a regional trial, with a focus on limited efficacy testing through an intermediate outcome (i.e., time to ROSC) that is strongly associated with survival. We also aim to evaluate the impact of the intervention on survival to hospital discharge, survival to hospital discharge with favourable neurological outcome, and safety in POHCA management. DISCUSSION: The PRIME trial aims to provide insight into the effectiveness and safety of IM epinephrine in POHCA. The data and analyses generated from the trial have the potential to inform resuscitation guidelines and standard of care practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT05166343, Registered on December 8, 2021.
Safety and efficacy of intradiscal nucleus pulposus allograft versus sham for lumbar discogenic pain associated with degenerative disc disease: study protocol for a randomized clinical trial.
Deer TR, Nunley PD, Naidu RK … +6 more , Beall DP, Davis TT, Calodney AK, Soin A, Lorio MP, Block JE
Trials · 2026 Jun · PMID 42260665 · Full text
BACKGROUND: Chronic low-back pain is a leading cause of global disability, with degenerative disc disease (DDD) recognized as a common structural contributor. While conservative therapies may provide temporary symptom re...
BACKGROUND: Chronic low-back pain is a leading cause of global disability, with degenerative disc disease (DDD) recognized as a common structural contributor. While conservative therapies may provide temporary symptom relief, they do not address the underlying degeneration of the intervertebral disc. Surgical interventions, such as spinal fusion or total disc replacement, are invasive procedures that permanently alter the anatomical structure of the vertebral motion segment. Minimally invasive intradiscal therapies have the potential to bridge the treatment gap between non-surgical management and surgery. Intradiscal delivery of nucleus pulposus (NP) allograft is intended to structurally supplement the degenerating disc and restore native disc function. Preliminary studies have suggested that a single intradiscal administration of NP allograft (VIA Disc NP) may improve pain and function in patients with lumbar discogenic pain. METHODS: This is a randomized, double-blind, sham-controlled, multi-center clinical trial designed to evaluate the safety and efficacy of VIA Disc NP. Eligible participants are 22 to 85 years of age with MRI-confirmed lumbar DDD (modified Pfirrmann grade 3-7), axial low-back pain of at least 6 months' duration, and functional impairment unresponsive to conservative treatment. Participants are randomized in a 2:1 ratio to receive either a single injection of VIA Disc NP or a sham procedure. The primary efficacy endpoint of this superiority trial is the proportion of participants achieving a ≥ 30% reduction in back pain severity at 12 months. Secondary endpoints include functional improvement (ODI), quality-of-life measures (EQ-5D-5L, PGIC), and opioid reduction. Sham participants who remain symptomatic at 12 months may cross over to receive active treatment. DISCUSSION: This trial will provide level-1 evidence of the safety and efficacy of supplemental NP allograft therapy in patients with moderate to severe lumbar discogenic pain. If successful, this approach may offer a minimally invasive, durable, and structure-preserving treatment alternative to spinal fusion or disc arthroplasty in a population with limited therapeutic options. TRIAL REGISTRATION: This trial is prospectively registered at ClinicalTrials.gov (Identifier: NCT06778447). Registered on January 16, 2025.
Rivaroxaban versus low-molecular-weight heparin and fondaparinux for preventing deep vein thrombosis after total knee arthroplasty in high-altitude residents: a randomized controlled trial.
Ren L, Fang H, Fu X … +4 more , Chu X, Liu X, Shi L, Zheng P
Trials · 2026 Jun · PMID 42260637 · Full text
BACKGROUND: High-altitude residence (defined as ≥ 1500 m above sea level) is associated with chronic hypoxia and increased thrombotic risk. This study aimed to evaluate the comparative efficacy and safety of rivaroxaban,...
BACKGROUND: High-altitude residence (defined as ≥ 1500 m above sea level) is associated with chronic hypoxia and increased thrombotic risk. This study aimed to evaluate the comparative efficacy and safety of rivaroxaban, low-molecular-weight heparin (LMWH), and fondaparinux for preventing deep vein thrombosis (DVT) after total knee arthroplasty (TKA) in long-term high-altitude residents. METHODS: In this randomized controlled trial, 90 high-altitude residents undergoing primary TKA were randomly assigned to one of three groups: rivaroxaban (group A), LMWH (group B), or fondaparinux (group C). The primary outcome was the incidence of postoperative DVT assessed by duplex ultrasonography on postoperative day 14. Secondary outcomes included coagulation indicators (PT, APTT, FIB, PLT, D-dimer), inflammatory markers (CRP, PCT, IL-6, ESR, WBC), knee circumference, intraoperative blood loss, and bleeding-related adverse events. RESULTS: DVT incidence was 0% in the rivaroxaban group, compared with 16.7% in the LMWH group and 13.3% in the fondaparinux group (P = 0.016). On postoperative day 14, D-dimer levels were significantly lower in the rivaroxaban group than in LMWH (P < 0.001) and fondaparinux (P < 0.001) and lower in fondaparinux than LMWH (P < 0.001). PT and APTT were higher in the rivaroxaban group compared with LMWH (PT P < 0.001, APTT P = 0.012) and fondaparinux (PT P < 0.001, APTT P = 0.035). FIB and PLT showed no significant differences. CRP and PCT were significantly lower with rivaroxaban than LMWH (CRP P < 0.001, PCT P < 0.001) and fondaparinux (CRP P = 0.018, PCT P = 0.018), while IL-6, ESR, and WBC showed no group differences. Intraoperative blood loss and bleeding complications were comparable across groups. CONCLUSION: Among high-altitude residents undergoing TKA, rivaroxaban demonstrated superior efficacy in preventing postoperative DVT and reducing inflammatory response without increasing bleeding risk. These findings contribute important evidence to guide anticoagulant selection in populations living at high altitude, who face unique thrombotic challenges due to chronic hypoxia.
Co-design of resources to support researchers to develop accessible and inclusive patient information leaflets for randomised controlled trials: the UK-based MAPLE project.
Wylde V, Johnson E, Roberts K … +4 more , Brennan S, Fulton T, Abdullahi N, Jameson C
Trials · 2026 Jun · PMID 42260534 · Full text
BACKGROUND: Low English language literacy and diverse communication needs are widespread in the UK. Provision of lengthy and complex patient information leaflets (PILs) for clinical trials can impose a barrier to researc...
BACKGROUND: Low English language literacy and diverse communication needs are widespread in the UK. Provision of lengthy and complex patient information leaflets (PILs) for clinical trials can impose a barrier to research participation. Inclusive research design incorporates providing clear and accessible written information, often in a layered approach. This project aimed to co-design resources to support researchers to create visual, inclusive, and accessible PILs for randomised controlled trials (RCTs). METHODS: Nineteen public and community involvement and engagement co-design workshops were held with nine groups, with a total of 150 attendees. Workshops were held with communities, patients, and charity representatives that are often marginalised in health research, including representation from racially marginalised communities, adults with learning disabilities and/or autism, adults with physical and mental health conditions, and the LGBTQIA+ community. A prototype modifiable accessible PIL was developed by the research team, designed using previously co-developed recommendations. During the first round of 10 workshops, a prototype accessible PIL was reviewed and discussed, and changes made to the phrasing, order, format, and layout. Additional feedback informed the development of guidance to researchers on the use of the accessible PIL. Suggestions for images for each section of the accessible PIL were collated and corresponding images sourced from online platforms. During the second round of nine co-design workshops, images were discussed and selected for inclusion, alongside recommendations for further edits and refinements to the accessible PIL and guidance to researchers. RESULTS: The co-design process resulted in substantial changes to the prototype accessible PIL. A suite of resources were developed, including an adaptable accessible PIL that can be downloaded and modified offline for each RCT, a selection of images from which researchers can choose images to purchase from platforms to include in their accessible PIL, and additional guidance on the use and modification of the accessible PIL. The resources are available at https://maple.bristol.ac.uk/. CONCLUSION: These co-designed practical resources aim to support researchers to create more accessible and inclusive written information to reduce English language literacy as a barrier to participation in RCTs, as part of a layered approach to information provision.
To adopt or adapt an existing COS for neonatal research: qualitative study.
Karumbi J, Gathara D, Williamson P … +1 more , Young B
Trials · 2026 Jun · PMID 42260531 · Full text
BACKGROUND: Core outcome sets (COS) standardise the outcomes reported in clinical trials and research, reducing outcome heterogeneity and enabling evidence synthesis. Most neonatal COS have been developed in high-income...
BACKGROUND: Core outcome sets (COS) standardise the outcomes reported in clinical trials and research, reducing outcome heterogeneity and enabling evidence synthesis. Most neonatal COS have been developed in high-income country (HIC) contexts and may not reflect the priorities, health system capacities, or disease burden of low- and middle-income countries (LMICs). Kenya's neonatal mortality rate remains high at 21 per 1000 live births, yet no COS exists for neonatal care and research in Kenya or, more broadly, in sub-Saharan Africa. This study aimed to develop a contextually appropriate COS for neonatal care and research in Kenya, and to assess the feasibility of adapting an existing HIC COS for use in an LMIC setting. METHODS: A mixed qualitative and consensus-based approach was used, guided by the COMET handbook. The process comprised three phases: a rapid review of outcomes reported in neonatal trials from sub-Saharan Africa compared with an existing HIC COS; qualitative stakeholder engagement through key informant interviews (KIIs) and focus group discussions (FGDs) with healthcare providers, national-level policymakers, and mothers of previously admitted neonates at two Kenyan hospitals representing urban and rural settings; and an in-person consensus workshop using the nominal group technique with 13 multidisciplinary stakeholders. Thematic analysis followed Braun and Clarke's six-phase framework. Outcomes endorsed by ≥ 70% of consensus meeting participants were included in the final COS. RESULTS: Seventeen stakeholders participated in KIIs, and 15 mothers participated in two FGDs. Sixteen candidate outcomes were presented at the consensus meeting. Five outcomes achieved immediate universal consensus: survival, length of hospital stay, ability to feed/weight gain/growth, cognitive ability, and visual impairment/retinopathy of prematurity (RoP). Following discussion and voting, a further seven outcomes were endorsed: impact on mothers and wider family, financial costs to the mother, pain, adverse events due to medicines, respiratory distress, quality of life, and sepsis/infections. The final COS comprises twelve outcomes. Seven overlapped with the existing HIC COS, though with contextually adapted definitions. Five outcomes are Kenya-specific, reflecting the out-of-pocket payment structure, high comorbidity burden, and family-centred care priorities of the Kenyan health system. CONCLUSIONS: Adapting an HIC neonatal COS for use in an LMIC context is feasible, but requires systematic definitional adaptation, engagement with existing local frameworks such as WHO Essential Newborn Care guidelines, and attention to diagnostic capacity constraints. The Kenya COS captures both clinical and life-impact outcomes, reflecting the priorities of diverse stakeholder groups including mothers. Realising its value requires phased implementation sensitive to urban-rural differences in facility capacity, investment in workforce training, and stronger collaboration between clinicians and researchers to ensure outcome measurement serves both care improvement and evidence generation. TRIAL REGISTRATION: This is not a clinical trial. CLINICAL TRIAL NUMBER: not applicable.
'They are with me on this journey', the importance of participant-researcher relationships on attendance at follow-up in a behavioural weight management trial: a qualitative study of participant perspectives.
Torrens C, O'Dolan C, MacLean A … +2 more , Ozakinci G, Farquharson B
Trials · 2026 Jun · PMID 42249492 · Full text
BACKGROUND: Retaining people for the duration of a trial or study can be challenging. This has been a particular difficulty for trials of behavioural weight management programmes. Poor retention can detrimentally impact...
BACKGROUND: Retaining people for the duration of a trial or study can be challenging. This has been a particular difficulty for trials of behavioural weight management programmes. Poor retention can detrimentally impact data quality, validity, reliability, and knowledge translation. A number of behavioural strategies (for example reminders or monetary rewards) have been implemented to improve retention at follow-up in trials. However, research in this area is limited, the evidence is uncertain, and has not considered wider strategies such as style of delivery or the role of participant-researcher relationships within trial processes. The aim of this qualitative study was to explore participant views and experiences of follow-up weight assessments. METHODS: Participants (n = 390) were randomised to protocolised weight assessments, scheduled at 3 and 6 months. These were implemented in an embedded study within a trial of a 12-month text-based behavioural weight management programme. Participants received a task-oriented approach focused on completing weight verification and the case report form or a relational approach focused on building the participant relationship. Assessments were delivered by researchers at three recruiting centres (Belfast, Bristol, and Glasgow). Framework method was used to analyse transcripts of semi-structured interviews with participants. RESULTS: Fifty-four trial participants took part in interviews. Three overarching themes were constructed from the narratives: the value of attending follow-up weight assessments, mode of weight assessment delivery, and contextual and practical factors influencing attendance at weight assessments. The themes provided novel insights into attendance at follow-up outcome assessments in a weight management trial including the emotive nature of attending weight assessments, related to weight stigma. Little distinguished the two groups. Participants spoke of positive relationships with researchers, benefitted from the researcher role within assessments, and desired in-person human contact, each considered by participants to enhance attendance. CONCLUSION: Participant-researcher relationships have an important role in retention. How researchers approach trial processes, such as outcome assessments, could improve attendance within weight management trials primarily by supporting motivation through mechanisms of change such as a sense of responsibility or accountability. Removal of connection through digital-only interventions, with limited in-person follow-up, has potential implications for retention. SWAT REGISTRATION: Northern Ireland Hub for Trials Methodology Research SWAT 147, 1/04/2020.
Remote, bivariate prior elicitation for a Bayesian non-inferiority randomized controlled trial.
Jiang A, Aregbesola A, Gangwani A … +9 more , Klassen TP, Plint AC, Doyle E, Craig W, Eltorki M, Oketola B, Badran H, Ouyang Y, Heath A
Trials · 2026 Jun · PMID 42249465 · Full text
BACKGROUND: Prior distributions must be specified for the parameters of interest in a Bayesian clinical trial. When existing evidence on the effects of the trial interventions is limited or inconclusive, prior distributi...
BACKGROUND: Prior distributions must be specified for the parameters of interest in a Bayesian clinical trial. When existing evidence on the effects of the trial interventions is limited or inconclusive, prior distributions can be constructed with expert elicitation. However, conventional elicitation requires face-to-face interactions and intensive pre-elicitation training, which can be infeasible and costly. Our remote elicitation was based on an established expert elicitation methodology, and we incorporated bivariate prior distributions to introduce dependencies between the elicited probabilities. We aimed to elicit a prior distribution for the Croup Dosing Trial, which assesses the efficacy of two separate doses of dexamethasone on the number of return visits to the emergency department within 7 days in children with croup. This trial evaluates the non-inferiority of 0.15 mg/kg of dexamethasone, compared to the standard dose of 0.60 mg/kg to treat croup. METHODS: We conducted three remote workshops to elicit expert beliefs on the efficacy of the two doses of dexamethasone. Each workshop consisted of two survey rounds, separated by a group discussion. Prior to the workshop, experts reviewed the same current literature that was provided on the effects of the two doses of dexamethasone. Beliefs were aggregated using expert-specific bivariate distributions with latent effects. The aggregated distribution, along with the surveyed non-inferiority margin, determined the sample size for the Bayesian non-inferiority trial design. RESULTS: Twelve emergency medicine physicians participated in our remote elicitation exercise. The elicitation generated a prior distribution centered at 6% for the 0.60 mg/kg dose and 8% for the 0.15 mg/kg dose. The aggregated prior distribution produced a sample size of 1850, based on a non-inferiority margin of 4%. CONCLUSIONS: We elicited a prior distribution that incorporated past evidence and expert opinion. The elicited prior is consistent with previous literature on the efficacy of the dexamethasone doses in treating croup. Our approach demonstrates the feasibility of remotely eliciting bivariate distributions to design clinical trials. TRIAL REGISTRATION: NCT06272383 (Registered May 8, 2024).
Fibrinogen concentrates versus cryoprecipitate for intraoperative hypofibrinogenemia in liver transplantation: study protocol for a randomized trial (FIBCRYO-LT trial).
Bang YJ, Oh CS, Lee DK … +6 more , Kang H, Kim KW, Kim H, Lee H, Kim TY, Kim GS
Trials · 2026 Jun · PMID 42243996 · Full text
BACKGROUND: Lyophilized factor concentrates, such as fibrinogen concentrate (FC), are considered superior to frozen products, such as cryoprecipitate, due to their rapid availability. Unlike frozen products, lyophilized...
BACKGROUND: Lyophilized factor concentrates, such as fibrinogen concentrate (FC), are considered superior to frozen products, such as cryoprecipitate, due to their rapid availability. Unlike frozen products, lyophilized factor concentrates do not require thawing or ABO blood type cross-matching, which can be time-consuming. We compared the time required for goal-directed management of hypofibrinogenemia using two strategies during liver transplantation (LT): a conventional cryoprecipitate-based strategy versus a lyophilized fibrinogen concentrate (FC)-based strategy. METHODS: This randomized trial will be performed in a tertiary university hospital from December 2025 to June 2026. Patients undergoing liver transplantation (LT) who provide written informed consents and develop intraoperative coagulopathy requiring fibrinogen supplementation-defined as serum fibrinogen < 100 mg/dL in standard central lab (SCL) tests or citrated functional fibrinogen maximum amplitude < 15 mm on thromboelastography (TEG6S™)-will be enrolled and randomized (1:1) to receive either cryoprecipitate (Group- C) or fibrinogen concentrate (Group- L). The primary outcome is an inter-group comparison of the treatment time (T-time, the duration from ordering cryoprecipitate or fibrinogen concentrate (FC) to completing its intravenous administration). Secondary outcomes include perioperative bleeding, blood transfusion requirements, coagulation profiles, reoperation, thromboembolic complications, mortality, oxygenation profiles, fibrinolysis phenotypes, bleeding-related costs, and length of hospital stay. DISCUSSION: A significantly shorter T-time in Group-L would support the superiority of the factor concentrate-based strategy for prompt intraoperative coagulation management during liver transplantation (LT). Its rapidity could reduce bleeding, transfusion requirements, and transfusion-related complications, thereby improving perioperative outcomes. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the registration number of NCT06144112 on November 16, 2023 ( https://classic. CLINICALTRIALS: gov/ct2/show/ NCT06144112).
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