Trials[JOURNAL]
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200 papers
Optimising a behavioural intervention to support endocrine therapy adherence for women with breast cancer: protocol for the ROSETA optimisation factorial randomised controlled trial.
Green SMC, McNaught E, Graham CD … +21 more , Dowse A, Wilkes H, Ow PL, Travis E, Foy R, French DP, Hall LH, Walwyn R, Day F, Taylor C, Carter A, Howdon D, Clark J, Waller J, Buxton J, Moore SJL, Parbutt C, Velikova G, Farrin A, Collinson M, Smith SG
Trials · 2026 May · PMID 42108483 · Full text
BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality. However, up to three quarters of women with breast cancer do not take AET as prescribed. Existing interventions to support adhe...
BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality. However, up to three quarters of women with breast cancer do not take AET as prescribed. Existing interventions to support adherence have shown limited effectiveness and often do not target the range of barriers to appropriate AET use. We developed four intervention components targeting barriers to AET adherence: Short Message Service (SMS) messages targeting forgetfulness, an information leaflet targeting medication beliefs, a self-management website targeting side-effects, and an acceptance and commitment therapy-based guided self-help programme targeting psychological flexibility. In the preparation phase of the Multiphase Optimisation Strategy (MOST), we conducted an external pilot optimisation trial. We met predefined progression criteria regarding consent, component adherence and availability of outcome measures, and concluded progression to an optimisation randomised controlled trial (O-RCT) was warranted. Our primary aim is to optimise the intervention package to support adherence to AET in women with early-stage breast cancer. METHODS: We will conduct a multi-centre, individually randomised superiority O-RCT using a 2 factorial design, with nested mixed-methods process and economic evaluations. We will randomise 512 women with early-stage breast cancer who have been prescribed AET to one of sixteen experimental conditions, operationalised as factors with two levels (on/off). Each condition is comprised of unique combinations of the intervention components. All participants will receive usual care. Our primary outcome is self-reported medication adherence at 12 months post-randomisation. Key secondary and process outcomes include quality of life, self-efficacy, habit formation, medication beliefs, psychological flexibility and distress, completed at 4, 8 and 12 months post-randomisation. Within the process evaluation, semi-structured interviews with participants will be conducted 5 and 13 months post-randomisation, and with trial therapists following intervention delivery. Cost per incremental quality-adjusted life year will be estimated in a health economic evaluation. DISCUSSION: Within the optimisation phase of the MOST framework, this trial, using a complex factorial design, will enable us to build a more effective, affordable, scalable and efficient intervention package to support AET adherence in women with breast cancer. This approach will advance intervention science by simultaneously testing the mechanisms through which the intervention components are operating. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN17334319. Registered on 02/02/2024.
Study protocol for a randomized, double-blind, placebo-controlled clinical trial of desidustat oral tablet in sickle cell disease: a phase IIa proof-of-concept evaluation.
Gangwar M, Kumar G, Roy S … +5 more , Gupta S, Parmar D, Kansagra K, Shah S, Mukherjee A
Trials · 2026 May · PMID 42106815 · Full text
BACKGROUND: Sickle cell disease (SCD) is a genetic disorder characterized by chronic hemolysis and vaso-occlusive crises. Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), has shown pro...
BACKGROUND: Sickle cell disease (SCD) is a genetic disorder characterized by chronic hemolysis and vaso-occlusive crises. Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), has shown promise in treating SCD by stimulating erythropoietin production in a similar manner that happens in response to hypoxia, promoting erythropoiesis and improving iron metabolism, leading to increased hemoglobin and RBC indices. METHODS: This was a phase IIa, double-blind, randomized, placebo-controlled, parallel-group, proof-of-concept, multicenter clinical trial designed to evaluate the efficacy and safety of desidustat in Indian adults with sickle cell disease (SCD). A total of 24 participants were enrolled based on predefined eligibility criteria, with 8 subjects per dose cohort (50 mg, 100 mg, and 150 mg), randomized in a 3:1 ratio (desidustat:placebo). The study included a screening period of up to 4 weeks, an 8-week treatment phase, and a follow-up visit at week 10, totaling 98 days. Efficacy (hemoglobin response rate) was assessed at week 8 relative to baseline compared to placebo. Dose adjustment of desidustat at week 4 was guided by hemoglobin levels measured using a calibrated HemoCue instrument. DISCUSSION: Management of sickle cell disease (SCD) has limited treatment modalities available like hydroxyurea and blood transfusions. They offer benefits but their limitations underscore the ongoing need for safer, more effective, and accessible treatments. This proof-of-concept trial was conducted to investigate the efficacy and safety of desidustat oral tablet, 3 times per week for 8 weeks in SCD patients. Results from this trial could aid in establishing a cost-efficient therapeutic option for managing rare diseases like SCD. TRIAL REGISTRATION: The study was approved by Central Drugs Standard Control Organization (CDSCO: CT NOC number CT/SND/27/2023, protocol number DESI.23.001, version no. 01 registered on 12 June 2023) and was conducted for a new drug as per the GCP guidelines. The first subject was screened on 7 January 2025 and the last visit of the last subject was conducted on 31 July 2025, followed by clinical study report finalization on 29 September 2025.
Tools to help patients and other stakeholders' input into choice of intercurrent event strategy for estimands in randomised trials.
Hindley J, Hartley C, Hellier J … +10 more , Sturgeon K, Greenwood S, Newsome I, Barrett K, Smith D, Pham TM, Bi D, Goulao B, Cro S, Kahan BC
Trials · 2026 May · PMID 42104488 · Full text
BACKGROUND: Estimands can help to clarify the research questions being addressed in randomised trials. Because the choice of estimand can affect how relevant trial results are to patients and other stakeholders, such as...
BACKGROUND: Estimands can help to clarify the research questions being addressed in randomised trials. Because the choice of estimand can affect how relevant trial results are to patients and other stakeholders, such as clinicians or policymakers, it is important for them to be involved in these decisions. However, there are barriers to having these conversations. For instance, discussions around how intercurrent events (post-randomisation events which affect the interpretation or existence of the outcome) should be addressed in the estimand definition typically involve complex concepts as well as technical language. We aimed to provide tools that could facilitate conversations between researchers and patients and other stakeholders about the choice of intercurrent event strategy for estimands. METHODS: We developed three tools: (i) a video explaining the concept of an estimand and the five different ways that intercurrent events can be incorporated into the estimand definition; (ii) an infographic outlining these five strategies; and (iii) an editable PowerPoint slide which can be completed with trial-specific details to facilitate conversations around choice of estimand for a particular trial. Each tool was produced through collaboration between researchers and public partners. This involved (i) an initial meeting between researchers and public partners to discuss the aims of the tool; (ii) a draft of the tool being prepared by the research team; (iii) public partners providing feedback; and (iv) the research team updating and finalising the tool. RESULTS: These resources can help to start conversations between the trial team and patients and other stakeholders about the best choice of estimand and intercurrent event strategies for a randomised trial. The video and infographic-which explain estimands and intercurrent events with reference to imagined examples-can be sent to stakeholders in advance of a consultation, or presented in the meeting itself. It is important that a member of the trial team is available to answer questions or clarify concepts following this. The editable slide can be completed by the trial team with the specific details of their trial, and then shown to patients or other stakeholders during the meeting to facilitate discussion around which intercurrent event strategy is most relevant for the trial. An example of a completed editable slide is also provided for an example weight loss trial. CONCLUSIONS: We developed three tools to help researchers to have conversations with patients and other stakeholders about estimands, and how intercurrent events should be incorporated into the target estimand for a randomised trial. Further work to evaluate the tools in real-world settings across different stakeholder groups could help to validate the tools and reveal any further refinements necessary to improve their utility.
Testing the biobehavioral regulation of negative emotion as a mechanism of change in transdiagnostic youth psychotherapy: study protocol for a randomized controlled trial.
Aitken M, Andrade BF, Krasinkiewicz CE … +10 more , Chan SWS, Gandhi SP, Pun JW, Hamilton-Wright A, Wang W, Sack L, Weisz JR, Bancroft R, Henderson J, Thomassin K
Trials · 2026 May · PMID 42104467 · Full text
BACKGROUND: Youth (i.e., child and adolescent) mental health difficulties are a prevalent concern, with anxiety, depression, and disruptive behavior disorders being the most common presentations. Even though psychotherap...
BACKGROUND: Youth (i.e., child and adolescent) mental health difficulties are a prevalent concern, with anxiety, depression, and disruptive behavior disorders being the most common presentations. Even though psychotherapy is often recommended to help youth and families manage mental health difficulties, recent meta-analyses suggest that youth psychotherapy is only moderately effective, highlighting a need for further improvement and innovation. Emotion dysregulation is a transdiagnostic risk factor across childhood emotional and behavioral disorders, yet despite the important connection between emotion regulation and psychopathology, little research has been conducted on emotion regulation as a potential mechanism of change during psychotherapy. This study will test the biobehavioral regulation of negative emotion as a transdiagnostic mechanism of change in youth psychotherapy using the Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH). MATCH is a well-researched therapy program for youth that is suitable for testing transdiagnostic mechanisms of treatment response. METHODS: This protocol describes a two-site randomized controlled trial that aims to recruit 202 youth between the ages of 8 to 15 years with anxiety, depression, and/or disruptive behavior. Participants are randomized to the MATCH intervention condition or a waitlist control condition. Youth and their parent(s) in both conditions complete in-lab assessments and online questionnaires at the start of the study, every 3 months (i.e., quarterly), and at post-test (i.e., following the intervention/waitlist period). Physiological measures of emotion regulation such as heart rate variability and skin conductance are acquired during lab-based tasks. Youth symptoms and emotion regulation are monitored weekly for both conditions. The primary outcome is change in youth symptoms of psychopathology at post-treatment, and whether this change is mediated by change in behavioral and physiological emotion regulation. Secondary outcomes include parental functioning, parenting, family functioning, impairment, and additional measures of youth psychopathology. DISCUSSION: Findings from the study are expected to enhance the understanding of processes that drive therapeutic change, ultimately leading to better therapy personalization and effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05637320. Prospectively registered on November 15, 2022. https://clinicaltrials.gov/study/NCT05637320 .
Publication bias and time to the publication of randomised trials conducted in sub-Saharan Africa: a cross-sectional study.
Hohlfeld A, Bennie LDM, Kredo T … +1 more , Clarke M
Trials · 2026 May · PMID 42098823 · Full text
BACKGROUND: Ideally, evidence-based decisions about healthcare interventions should be informed by access to up-to-date information from all relevant RCTs, making it essential that the reports are published soon after st...
BACKGROUND: Ideally, evidence-based decisions about healthcare interventions should be informed by access to up-to-date information from all relevant RCTs, making it essential that the reports are published soon after study completion. However, studies have consistently shown that between 25 and 50% of clinical trials remain unpublished or are only published many years after completion. The WHO has noted a slow but steady increase in the number of RCTs since the mid-2000s, particularly in sub-Saharan Africa (SSA). However, the extent of publication bias of SSA RCTs remains unknown. Therefore, our study objectives were to assess (1) the proportion of completed RCTs from SSA that have been published and (2) the time from completion to publication. METHODS: This cross-sectional study, consisting of a retrospective analysis of registered SSA RCTs, aims to report the proportion of completed and terminated SSA RCTs registered in ClinicalTrials.gov and the Pan African Clinical Trials Registry (PACTR) and their time to publication. RESULTS: Our search yielded 7896 records, of which 3026 RCTs met our inclusion criteria for analysis. We identified journal publications for 1983 (65.5%) RCTs. The overall median time to publication from the primary completion date was 34.2 months (95% CI: 32.4 to 35.5). CONCLUSIONS: Overall, we found a substantial proportion (34.5%) of unpublished SSA RCTs. Moreover, the median time to publication from primary completion was 34.2 months. The persistence of publication bias threatens the integrity of evidence-based healthcare practice, particularly given that consumers depend on peer-reviewed journal publications as conventional and trusted sources to stay informed. Our findings underscore the importance of continued research to test and implement preventative strategies to mitigate publication bias.
Challenges of delivering a lifestyle intervention before surgery in multiple surgical specialties in the NHS: experience from the INSPIRE trial.
Bridgeman E, Beard C, Joyce K … +4 more , Levett D, Phillips D, Pufulete M, Culliford L
Trials · 2026 May · PMID 42098807 · Full text
This paper describes the challenges of undertaking a trial of a pre-operative lifestyle intervention in multiple surgical specialties, the INSPIRE trial, and additional challenges of doing so during the COVID-19 pandemic...
This paper describes the challenges of undertaking a trial of a pre-operative lifestyle intervention in multiple surgical specialties, the INSPIRE trial, and additional challenges of doing so during the COVID-19 pandemic. The INSPIRE trial was a randomised controlled trial to test if inspiratory muscle training could reduce the incidence of postoperative pulmonary complications in patients undergoing cardiac, thoracic and abdominal elective surgery. We present the challenges of trial conduct alongside the adaptations introduced to mitigate the impact of those challenges. The INSPIRE trial was halted by the funder at the end of the internal pilot phase. We were therefore unable to assess the effect of some of the adaptations, and there were further adaptations we were unable to make. We are using our experience to make recommendations for future similar trials.
Existential distress in advanced cancer: study protocol of a pragmatic randomized controlled trial of a short-term psychodynamic therapy (ORPHYS) compared to usual psycho-oncological treatment (TAU).
Philipp R, Walbaum C, Bokemeyer C … +14 more , Dinger U, Härter M, Hemsen B, Holsteg S, Karger A, Koch U, Kriston L, Lezius S, Lindner R, Maatouk I, Oechsle K, Scholl I, Wagner A, Vehling S
Trials · 2026 May · PMID 42098804 · Full text
BACKGROUND: As improvements in anti-cancer treatments have extended survival, patients with advanced cancer and their family caregivers face existential tension between engaging in life and coping with uncertainty about...
BACKGROUND: As improvements in anti-cancer treatments have extended survival, patients with advanced cancer and their family caregivers face existential tension between engaging in life and coping with uncertainty about illness trajectory and the course of treatment. For a subgroup, this tension is associated with overwhelming fear and existential distress. Such adjustment difficulties may increase the risk of mental disorders, poor quality of life, and suicidality, and impair prognostic awareness and patient-clinician communication. Despite growing interest in open conversations about end-of-life issues, systematic evidence on effective psychotherapies to best support psychological adaptation in patients with high levels of existential distress is still scarce. We aim to evaluate the effectiveness of a short-term psychodynamic therapy (ORPHYS) to mitigate existential distress compared to usual psycho-oncological treatment (TAU). METHODS: We conduct a two-arm parallel randomized controlled trial with an active control group. ORPHYS is a manualized individual face-to-face psychotherapy focusing on emotional and relational conflicts specific to cancer patients' illness situation. Treatment lasts between 5 and 11 months with 15 to 31 weekly sessions (50 min). TAU includes at least one individual session provided by physicians or psychologists with experience in psycho-oncological care. Patients will be assessed pre-intervention and 3, 6, 9, and 12 months after baseline. Target sample size is 160 randomized participants. We recruit patients with stage III/IV solid tumors or advanced hematological cancer and clinically significant existential distress from psycho-oncology clinics and referring oncologists at Hamburg, Düsseldorf, and Würzburg Comprehensive Cancer Centers, Germany. The primary outcome is demoralization (Demoralization Scale-II). Secondary outcomes include diagnoses of affective, anxiety and stress-related disorders, death anxiety, dignity-related distress, and quality of life. Outcome assessments are conducted via self-report questionnaires and diagnostic interviews. Linear mixed models examine outcome differences between trial arms. A confirmatory test of the group contrast at 6-month follow-up after baseline is conducted. DISCUSSION: Due to an aging population and prolonged survival, there is a growing demand to help patients deal with existential challenges undergoing palliative cancer care. The study will contribute to knowledge about how clinicians can best help patients with advanced cancer who substantially struggle with uncertainty at the end of life. TRIAL REGISTRATION: German Clinical Trials Registry, DRKS00038173. Registered October 20th, 2025, https://drks.de/search/en/trial/DRKS00038173 . CLINICALTRIALS: gov, NCT07312760. Registered December 30, 2025, https://clinicaltrials.gov/study/NCT07312760 .
The REACT MCI study: a randomized controlled clinical trial on the effect of repeated advanced cognitive training in mild cognitive impairment.
Hernes SS, Nordnes PR, Hol HR … +6 more , Ringstad G, Knapskog AB, Emhjellen P, Løhaugen G, Emini M, Edwin TH
Trials · 2026 May · PMID 42098801 · Full text
BACKGROUND: Mild cognitive impairment (MCI) and its course have multiple determining factors with both detrimental and compensatory processes in the brain. Computerized working memory training can improve cognitive funct...
BACKGROUND: Mild cognitive impairment (MCI) and its course have multiple determining factors with both detrimental and compensatory processes in the brain. Computerized working memory training can improve cognitive function and individuals with MCI are potential targets. Since more than 1/3 of these individuals develop dementia within 5 years, any intervention postponing the progression will be immensely important. We aim to investigate the efficiency and cost-effectiveness of working memory training in MCI. METHODS: In this blinded randomized controlled trial, 213 participants will be allocated to three groups: (1) one 5-week period of working memory training, (2) two 5-week periods of working memory training, or (3) the active control group. The participants are followed for a period of 48 months (3, 6, 12, 24, and 48 months). Furthermore, we investigate microstructural effects of working memory training on magnetic resonance imaging and seek to identify high responders to training by assessing the association with function in the glymphatic system and genetic variations. Finally, the impact of working memory training on quality of life and relatives' stress, and whether it is a cost-effective approach in MCI, will be assessed. DISCUSSION: Effective therapy for MCI is lacking. Finding an intervention postponing the progression of MCI is of great importance for patients as well as for the global economy and health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04792528. Registered on 02.23.2021.
A randomised controlled trial of physical activity and cognitive training in older adults: the PhABHeaD study.
Cherbuin N, Northey JM, Walsh EI … +11 more , Burns RA, Speer H, Lawlis N, Namsrai T, Scott A, McCarthy V, Lane J, van Boxtel JJA, Lampit A, Brüstle A, Rattray B
Trials · 2026 May · PMID 42098784 · Full text
BACKGROUND: Robust empirical evidence supports the effectiveness of physical and cognitive training in preventing and delaying cognitive decline. Emerging research suggests distinct neurobiological mechanisms underpin th...
BACKGROUND: Robust empirical evidence supports the effectiveness of physical and cognitive training in preventing and delaying cognitive decline. Emerging research suggests distinct neurobiological mechanisms underpin the effects of these different training modalities. An unresolved question is whether the mechanisms through which these training modalities impart their effect interact synergistically to improve cognitive outcomes, rather than exerting additive effects, differ. In addition, past research has been inconsistent in adequately controlling for or documenting the dosage of physical and/or cognitive training. Consequently, the aim of this study is to assess the relative effectiveness of physical and cognitive training conducted in isolation or concurrently, whilst rigorously controlling and documenting the treatment parameters. METHODS: This study is a three-arm randomised controlled trial conducted over a 3-month period, comparing cognitive training, physical activity, and a combination of both interventions. Older cognitively healthy participants (n = 126) aged 60-75 years will be recruited from the community. The physical only training will require participants to cycle on a cycle ergometer at above 60% of their age-predicted heart rate maximum for 50 min with a 3-min warm-up and cool-down period. The cognitive only training will require participants to complete up to five different cognitive tasks selected from a set of eight on the BrainHQ platform during each 50-min training session. The concurrent cognitive and physical training will require participants to undertake both treatments at the same time. Primary outcomes, assessed pre- and post- intervention, will include speed of processing and episodic memory assessed with the NIH Toolbox, as well as general driving skills assessed on a driving simulator. DISCUSSION: Findings will inform the design of interventions and population health advice aimed at mitigating cognitive decline. If a substantial synergetic effect is detected, it may lead to the use of more widespread concurrent physical and cognitive training and the potential development of methods to make concurrent training practical. Findings will also provide important clarification as to the relative benefit of the two modes of training. TRIAL REGISTRATION: Prospective registration with Australia and New Zealand Clinical Trial Registry (ACTRN12624001088538) on 10th September 2024 and World Health Organisation International Clinical Trials Registry (U1111-1280-3851).
Reperfusion thrombolytic therapy for ischemic stroke in patients on non-vitamin K antagonist oral anticoagulants: study protocol of a phase II randomized clinical trial.
Karaszewski B, Jabłoński B, Gąsecki D … +2 more , Szczyrba S, Wyszomirski A
Trials · 2026 May · PMID 42093017 · Full text
BACKGROUND: Cardioembolic stroke accounts for more than 20% of all acute ischemic strokes (AIS) and is mainly caused by cardiac arrhythmias, particularly atrial fibrillation (AF). The presence of specific or multiple add...
BACKGROUND: Cardioembolic stroke accounts for more than 20% of all acute ischemic strokes (AIS) and is mainly caused by cardiac arrhythmias, particularly atrial fibrillation (AF). The presence of specific or multiple additional vascular risk factors indicates the need for oral anticoagulant (OAC) therapy in AF patients (according to the CHA2DS2-VASc classification). While OAC treatment significantly reduces the risk of AIS by over 80% in this population, the risk remains higher compared to the general population. Approximately half of AF patients on OAC therapy who experience AIS do not meet the criteria for thrombolytic (high blood activity of OAC) or mechanical thrombectomy (non-large vessel occlusion stroke) treatment. AIM: This study aims to assess the efficacy and safety of recombinant tissue plasminogen activator (rtPA) in AIS patients who have been on chronic non-vitamin K antagonist oral anticoagulant (DOAC) therapy after receiving a specific reversal agent. METHODS AND DESIGN: Patients with acute ischemic stroke (AIS) who are treated with specific oral anticoagulants (OACs) with anti-Xa activity have been on chronic non-vitamin K antagonist oral anticoagulant e included in the study. The protocol involves administering a fast-acting antidote (andexanet alfa for rivaroxaban or apixaban) or a placebo, followed by intravenous thrombolytic therapy with rtPA or a placebo. The study arms for rivaroxaban and apixaban are designed as prospective, randomized, placebo-controlled interventional trials that meet phase II trial criteria. DISCUSSION: The STRoke on Oral AntiCoagulants for Thrombolysis (STROACT) trial is, to our knowledge, the first randomized phase II study designed to explore the feasibility, efficacy, and safety of reversal-enabled intravenous thrombolysis in a highly selected population of acute ischemic stroke patients on factor Xa inhibitors. The results are expected to be hypothesis-generating and may inform the design of future confirmatory trials. TRIAL REGISTRATION: www.clinicaltrialsregister.eu ; EudraCT Nr: 2020-004898-41; March 31, 2021.
Impact of the gut microbiome on health impacts of Haskap berries: study protocol for a randomized control trial.
Chamberlin ML, Spears ML, Cooper G … +5 more , Miller ZJ, Bothner B, Walk ST, Yeoman CJ, Miles MP
Trials · 2026 May · PMID 42087172 · Full text
BACKGROUND: Haskap berries have great potential as a superfood due to high polyphenolic content which confers both anti-inflammatory and antioxidant activity. These health impacts are mitigated, at least in part, by the...
BACKGROUND: Haskap berries have great potential as a superfood due to high polyphenolic content which confers both anti-inflammatory and antioxidant activity. These health impacts are mitigated, at least in part, by the gut microbiome as most ingested polyphenols pass to the large intestine for microbial enzymatic action and conversion to secondary phenolic metabolites. These microbial actions mediate both the bioavailability and the bioefficacy of Haskap-derived phenolics. However, clinical intervention trials characterizing the impact of long-term Haskap consumption on human health and the interaction between Haskap-derived phenolics and the gut microbiome are limited. This study aims to determine the impact of Haskap consumption on gut microbiome composition, gut microbial and serum metabolites, and other health outcome metrics in a cohort of adults with both low and high risk of metabolic syndrome. METHODS: This is a four-armed, randomized, triple-blind, placebo-controlled clinical trial conducted in a cohort of adults with both low and high risk of metabolic syndrome. A total of 120 participants (60 metabolically healthy, 60 metabolically unhealthy) will be randomized in a 1:1 ratio to consume a daily dose of either Haskap or placebo juice for 8 weeks. Outcome measures will be collected before and after the intervention period to determine the health impacts of Haskap in both groups. Primary outcome measures include fasting blood markers of glucose and lipid metabolism and inflammation, fat oxidation rates during submaximal exercise, 16S rRNA fecal microbial composition data, and mass spectrometry-acquired fecal and serum metabolomic data. Secondary outcome measures include anthropometric and sleep quality measures as well as acute and habitual dietary intake data. DISCUSSION: Investigating how the gut microbiome influences the health benefits of consuming Haskap berries will help elucidate potential mechanisms of Haskap-induced metabolic health benefits and help inform the development of effective strategies to decrease metabolic disease risk through Haskap consumption. TRIAL REGISTRATION: ClinicalTrials.gov NCT06546020. Registered on 1 August 2024.
Postoperative drainage after pancreatoduodenectomy: a randomized controlled trial among patients with intermediate and low risks for pancreatic fistula-DRAIN1.
Wallon S, Williamsson C, Karlsson V … +5 more , Wennerblom J, Bratlie SO, Sandström P, Tingstedt B, Björnsson B
Trials · 2026 May · PMID 42083018 · Full text
BACKGROUND: Routine use of surgical drains after abdominal operations has largely been abandoned over the past decades. Studies have failed to demonstrate benefits of routine drainage following liver, gallbladder, gastri...
BACKGROUND: Routine use of surgical drains after abdominal operations has largely been abandoned over the past decades. Studies have failed to demonstrate benefits of routine drainage following liver, gallbladder, gastric, and colorectal surgeries. Until recently, intraoperative placement of abdominal drains was the gold standard in pancreatoduodenectomies (PDs) due to concerns about uncontrolled postoperative pancreatic fistula (POPF). A large randomized trial in 2014 reported increased mortality in patients without postoperative drain placement. However, as the study did not stratify participants based on their preoperative risk of developing a POPF, further research is needed. Limited evidence from a non-randomized cohort suggests that omitting drains may be safe in very low-risk settings. However, a larger comparative study, including a broader range of PD cases, is necessary to confirm these findings. METHODS: This is a two-arm, randomized, controlled, non-blinded, multicenter trial comparing intra-abdominal drain placement with no drain placement during planned pancreatoduodenectomies (PDs). Eligible patients who meet the inclusion criteria will be assessed for their individual risk of postoperative pancreatic fistula (POPF) using a risk scoring system. They will then be randomized into either the drain placement or no drain placement group. The groups will be compared using the chi-square test for categorical variables and Fisher's exact test. Logistic regression models will be used to calculate odds ratios for morbidity. Univariable and multivariable models will assess the impact of drain placement on clinical outcomes. DISCUSSION: This trial aims to determine whether omitting routine intraoperative drain placement reduces the risk of complications in patients undergoing pancreatoduodenectomy (PD). It will provide level 1 evidence on the association between routine intra-abdominal drainage and postoperative complications in patients with a low to intermediate risk of developing a postoperative pancreatic fistula (POPF). The findings will contribute to future treatment guidelines by expanding the available knowledge on optimal drainage strategies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05270564. Registered on February 16 2022.
Methodological changes made to NIHR-funded randomised controlled trials: review of 100 trials.
Mott A, Fitzmaurice E, Watson J … +1 more , McDaid C
Trials · 2026 May · PMID 42071217 · Full text
BACKGROUND: Previous studies have reviewed protocol amendments to trial methods in commercial studies and single centres. These studies identified that many were avoidable changes. This study aimed to assess the types of...
BACKGROUND: Previous studies have reviewed protocol amendments to trial methods in commercial studies and single centres. These studies identified that many were avoidable changes. This study aimed to assess the types of changes and rationale for changes in publicly funded randomised controlled trials undertaken in the UK. METHODS: The most recent 100 published randomised controlled trials, on 23rd June 2024, in two NIHR Journals (Health Technology Assessment and Efficacy and Mechanism Evaluation), were selected for review. Data was collected on trial characteristics and the changes reported in the protocol, published reports, and trial registry entry. RESULTS: Of the 100 included trials, 90 reported changes to the methods. A total of 846 methodological changes were recorded; 45.49% of the recorded changes occurred within the first year of study conduct. A rationale was provided for 204 of the changes with 39 unique reasons given. Frequent reasons for the changes were oversight committee recommendations, site feedback, COVID, and alignment with clinical guidance. The changes were not universally reported across the report, protocol, and registry entry and less than half were reported on the trial registry. CONCLUSIONS: The majority of NIHR-funded trials make methodological changes throughout the duration of the trial, with a large proportion being made within the first year. Consideration should be given to whether a change in the way trials are designed and planned could reduce the need for changes early on. The reporting of methodological changes also needs improvement to ensure trial documentation is consistent and up to date. TRIAL REGISTRATION: This project was registered on the OSF registry, the details of the registration are available here: https://doi.org/10.17605/OSF.IO/WV2GX . Registered on July 22 2024.
Bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir plus lamivudine plus tenofovir disoproxil fumarate in people living with HIV experiencing virologic failure in China: a study protocol for a multicenter, open-label, randomized controlled non-inferiority trial.
Wang R, Ren Y, Li R … +7 more , Liu H, Liu X, Hua W, Wang X, Cao Y, Sun L, Dai L
Trials · 2026 May · PMID 42067921 · Full text
BACKGROUND: In China, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens remain widely utilized as first-line antiretroviral therapy (ART) despite issues of low resistance barriers and significant side...
BACKGROUND: In China, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens remain widely utilized as first-line antiretroviral therapy (ART) despite issues of low resistance barriers and significant side effects, leading to frequent treatment interruptions and virologic failures. Timely drug-resistance testing is often inaccessible, complicating subsequent treatment management. This trial aims to fill this critical gap by comparing the efficacy, safety, and tolerability of the single-tablet regimen (STR) of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) with the multi-tablet regimen (MTR) of dolutegravir plus lamivudine plus tenofovir disoproxil fumarate (DTG+3TC+TDF) in people living with HIV (PLWH) experiencing virologic failure. METHODS: This multicenter, open-label, randomized controlled non-inferiority trial will enroll 374 PLWH experiencing virologic failure of first-line NNRTI-based therapy from 14 clinics across China. Participants will be randomized 1:1 to receive either a once-daily STR of BIC/FTC/TAF or a once-daily MTR of DTG+3TC+TDF. The primary endpoint is the proportion achieving viral suppression (HIV-1 RNA < 50 copies/mL) at week 48. Secondary endpoints include the time to viral suppression, emergence of resistance-associated mutations (RAMs), immunologic markers, treatment adherence, patient-reported outcomes, and safety profiles. Data will be analyzed using intention-to-treat (ITT) and per-protocol (PP) populations, with non-inferiority defined using a margin of 12%. DISCUSSION: This trial aims to provide high-quality evidence for a simplified, high-barrier, STR as an optimized second-line strategy in resource-limited settings where drug resistance testing is inaccessible. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Trial ID: ChiCTR2500108287). Registered on 27 August 2025. Retrospectively registered. https://www.chictr.org.cn .
AdoHealth e-wellness initiative for adolescent non-communicable disease risk reduction: protocol for a school-based cluster randomised controlled trial in SAS Nagar (Mohali), Punjab, India.
Virk A, Lal D, Sharma S … +6 more , Goel A, Bhardwaj A, Nadda A, Kumar A, Bharti B, Singh S
Trials · 2026 May · PMID 42063181 · Full text
BACKGROUND: Non-communicable diseases (NCDs) increasingly affect adolescents, particularly in low- and middle-income countries. Seven key lifestyle behaviours, alcohol and tobacco use, consumption of JUNCS foods (junk, u...
BACKGROUND: Non-communicable diseases (NCDs) increasingly affect adolescents, particularly in low- and middle-income countries. Seven key lifestyle behaviours, alcohol and tobacco use, consumption of JUNCS foods (junk, ultra-processed, nutritionally inappropriate, caffeinated/coloured/carbonated foods/beverages, sugar-sweetened beverages); physical inactivity; inadequate sleep; excessive screen time; and stress, collectively termed the 'Big-7 Behavioural Risk Determinants', contribute to NCD onset in adolescence and persistence into adulthood. OBJECTIVE: To determine the effectiveness of the AdoHealth e-wellness initiative in reducing the Big-7 Behavioural Risk Determinants among school-going adolescents aged 14-17 years, measured as change from baseline at 6 and 12 months post-intervention compared with control schools. METHODS: This multisite, open-label, superiority cluster randomised controlled trial will include 180 high and senior secondary schools (Classes 9-12, ages 14-17 years; including public and private) in SAS Nagar (Mohali), Punjab, India, randomly assigned in a 1:1 ratio to intervention or control groups, stratified by school location (urban/rural) and school type (government/private). Participants will be recruited by trained field investigators. Eligible participants are students aged 14-17 years enrolled in participating schools, with written parental consent and adolescent assent; students with serious health conditions or planned school transfer will be excluded. The intervention comprises e-modules (10-15 min each) on the Big-7 Behavioural Risk Determinants, delivered via classroom smartboards with facilitator support, over 8 weekly sessions. A pilot phase will be conducted in one school (approximately 100 adolescents) prior to full-scale implementation. Behavioural and biochemical assessments using standardised tools will be conducted at baseline, 6 months, and 12 months post-intervention. Safety monitoring includes adverse event reporting and referral for psychological support as needed. The planned sample size is 18,000 students (9000 per arm across 90 clusters each). The primary endpoint is the change in the 'Big-7 Behavioural Risk Determinants' at 12 months post-intervention, while secondary endpoints include intermediate behavioural changes, biochemical risk markers, and overall well-being. EXPECTED IMPACT: This study aims to evaluate the feasibility and potential effectiveness of school-based e-wellness interventions targeting multiple health behaviours simultaneously. If successful, findings may contribute to early NCD prevention strategies and inform policy development for adolescent health promotion programs in low- and middle-income countries. TRIAL REGISTRATION STATEMENT: Trial registration: Clinical Trials Registry of India (CTRI), CTRI/2025/01/079797. Registered on January 30, 2025. https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=121397&EncHid=98502.11769&modid=1&compid=19 . First participant recruitment commenced on August 16, 2025.
Ivermectin therapy is associated with changes in SARS-CoV-2 RNA load in asymptomatic patients: a randomized controlled trial.
Mouawia H, Saab HB, Ayoub H … +5 more , Mourad A, Yaghi N, Al Saabi A, El-Seblani M, Raad H
Trials · 2026 May · PMID 42063155 · Full text
BACKGROUND: Ivermectin, an antiparasitic agent with reported antiviral properties, has been investigated for repurposing in the treatment of COVID-19. This study aimed to assess the efficacy of a single weight-adjusted o...
BACKGROUND: Ivermectin, an antiparasitic agent with reported antiviral properties, has been investigated for repurposing in the treatment of COVID-19. This study aimed to assess the efficacy of a single weight-adjusted oral dose of ivermectin in reducing viral load and improving clinical outcomes in asymptomatic individuals infected with SARS-CoV-2. METHODS: A randomized controlled trial was conducted with 126 asymptomatic SARS-CoV-2-positive participants. Subjects were assigned to receive either standard care (zinc and vitamin C supplementation) or standard care plus a single dose of ivermectin. Reverse transcription-PCR was used to assess changes in cycle threshold (Ct) values after 96 h. Clinical symptom development and hospitalization rates were also monitored. RESULTS: Baseline Ct values were similar between groups. After 96 h, participants in the ivermectin group showed a greater increase in Ct values (from 15.97 ± 2.823 to 24.35 ± 3.086) compared with controls (from 16.65 ± 3.593 to 19.84 ± 3.743; p < 0.001), the mean increase in Ct was 8.38 (95% CI, 7.56-9.20) in the ivermectin group versus 3.19 (95% CI, 2.36-4.02) in the control group (mean difference 5.19 (95% CI, 3.72 to 6.66); p < 0.001), suggesting a potential for more rapid reduction in viral load. Participants receiving ivermectin also reported fewer symptoms (e.g., anosmia, fatigue, myalgia) and had a lower hospitalization rate, though these clinical trends should be interpreted cautiously. CONCLUSION: A single oral dose of ivermectin may accelerate viral clearance and reduce symptom progression in asymptomatic SARS-CoV-2-positive individuals. Further large-scale, multi-center randomized trials are warranted to confirm these findings and evaluate ivermectin's potential role in early COVID-19 management. TRIAL REGISTRATION: This randomized controlled trial was conducted between November and December 2021 and was registered in the World Health Organization Clinical Trial Registry (ChiCTR2000033627; Date of Registration: 2020-06-07).
Early secondary outcome analysis in multi-phase randomised-controlled trials, a pragmatic approach: the Healthy Life Trajectories Initiative (HeLTI).
Kumaran K, Baillargeon JP, Birken CS … +9 more , Dennis CL, Fan J, Fraser WD, Huang H, Hung RJ, Suryanarayana KG, Lye SJ, Norris SA, Matthews SG
Trials · 2026 Apr · PMID 42057197 · Full text
BACKGROUND: The extended time frame of some trials can cause significant challenges in delaying all analyses until the primary outcome is attained. This may particularly affect any mechanistic studies linked to secondary...
BACKGROUND: The extended time frame of some trials can cause significant challenges in delaying all analyses until the primary outcome is attained. This may particularly affect any mechanistic studies linked to secondary outcomes, as well as impact the involvement of trainees and junior investigators in the project. This manuscript describes the strategy and process by which the leadership of the Healthy Life Trajectories Initiative (HeLTI) developed an analysis approach. METHODS: The study involved the engagement of an expert panel with broad knowledge in disciplines relevant to the study. RESULTS: Several reviewers emphasised the importance of undertaking analysis only after the primary outcome has been achieved. However, the majority of reviewers highlighted that this was not practical in the context of the HeLTI consortium because valuable interim analysis would be missed. CONCLUSION: After careful consideration of the issue and feedback received, the HeLTI leadership agreed to an approach that allowed publishing between-group comparisons of secondary outcomes and linked mechanistic studies before the primary outcome, using an a priori agreed phased approach.
Efficacy of transcutaneous spinal cord stimulation combined with resistance training on motor function in motor-incomplete spinal cord injury: protocol for an open-label, single-blind randomized controlled trial.
Chen J, Luo X, Zhang Y … +8 more , Li Y, Wang Y, Ye J, Sun J, Huang H, OuYang Z, Yuan Y, Wang Y
Trials · 2026 Apr · PMID 42057082 · Full text
BACKGROUND: Spinal cord injury (SCI) commonly results in substantial motor impairments, particularly in standing and walking abilities, due to the disruption of the sensory-motor circuits. Conventional rehabilitation app...
BACKGROUND: Spinal cord injury (SCI) commonly results in substantial motor impairments, particularly in standing and walking abilities, due to the disruption of the sensory-motor circuits. Conventional rehabilitation approaches have limited effectiveness in restoring motor function. The present study investigates the combined effects of transcutaneous spinal cord stimulation (tSCS) and resistance training (RT) on improving motor function in patients with motor-incomplete SCI. Furthermore, it examines the underlying mechanisms of these improvements through the use of advanced neuroimaging and electrophysiological techniques. METHODS: This open-label, single-blind, randomized controlled trial will be conducted over 28 days at Shanghai Yangzhi Rehabilitation Hospital. A total of 56 participants with motor-incomplete SCI will be randomly assigned to two groups: the intervention group (tSCS + RT) and the control group (RT only). The intervention group will receive tSCS in combination with RT 3 times per week for 4 weeks, while the control group will undergo RT without tSCS. Primary outcomes will include peak torque measurements and secondary outcomes will involve motor functions and multimodal neurofunctional metrics. Data will be analyzed to evaluate the efficacy of the combined treatment in improving lower limb motor function. DISCUSSION: The novel combination of tSCS and RT aims to enhance motor function by providing dual-channel neuromodulation that targets both sensory and motor pathways. The results of this study could inform future therapeutic strategies and the broader clinical application of neuromodulation technologies in spinal cord injury rehabilitation. TRIAL REGISTRATION: This study was prospectively registered at the Chinese Clinical Trials Registry, ChiCTR2400089603, registered on September 11, 2024, https://www.chictr.org.cn .
Effectiveness and mechanisms of digital cognitive and physical function prehabilitation for improving prognosis in kidney transplant recipients: protocol for a randomised controlled trial.
Ma X, Petersen JD, Yao B … +5 more , Chen R, Zhi T, Guo Y, Bai D, Jiang H
Trials · 2026 Apr · PMID 42050736 · Full text
INTRODUCTION: Frailty and cognitive impairment are highly prevalent among patients on the kidney transplant waitlist (KTWs), contributing to poor post-transplant outcomes. While digital health interventions have shown pr...
INTRODUCTION: Frailty and cognitive impairment are highly prevalent among patients on the kidney transplant waitlist (KTWs), contributing to poor post-transplant outcomes. While digital health interventions have shown promise in chronic disease management, their application as a comprehensive prehabilitation tool for KTW patients remains largely unexplored. This study aims to evaluate the effectiveness of a digital cognitive and physical prehabilitation program in improving the prognosis for KTW patients. Furthermore, it seeks to investigate the underlying biological mechanisms, focusing on the inflammation-muscle-brain axis. METHODS: This single-center, assessor-blinded, randomized controlled trial will enroll 100 eligible KTW patients. Participants will be allocated (1:1) to either an intervention group or an active control group. The control group will receive standard care plus a digital platform for daily health management. The intervention group will receive, in addition, a 12-week, home-based program of digitally supervised exercise (aerobic and resistance) and cognitive training. RESULTS: The primary outcomes will include changes in physical function (evaluated through the 6-min walk test, sit-to-stand test, timed up-and-go test, and handgrip strength) and cognitive function (assessed using the Montreal Cognitive Assessment and Digit Symbol Substitution Test). Key clinical transplant outcomes, such as delayed graft function, graft survival, patient survival, and rejection episodes, will also be assessed. Secondary outcomes will encompass longitudinal changes in biomarkers related to the inflammation-muscle-brain axis (including inflammatory cytokines, myokines, and neurological markers), as well as patient-reported quality of life (SF-36) and vascular function (brachial-ankle pulse wave velocity). CONCLUSION: This study will provide critical evidence on the implementation of a multimodal digital prehabilitation strategy in KTW patients. The results are expected to inform future clinical guidelines and offer a scalable model to optimize pre-transplant fitness. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) identifier number: ChiCTR2500104025. Registered on 10 June 2025.
Transcutaneous tibial nerve stimulation versus sham stimulation for the treatment of catheter-related bladder discomfort in patients undergoing transurethral resection of the prostate: a prospective, randomized, placebo-controlled, double-blind trial.
Song Y, Sun X, Mei L … +2 more , Wang Y, Song J
Trials · 2026 Apr · PMID 42050700 · Full text
BACKGROUND: Catheter-related bladder discomfort (CRBD), characterized by urinary urgency, frequency, and suprapubic pain, is a clinically significant complication following transurethral resection of the prostate (TURP)....
BACKGROUND: Catheter-related bladder discomfort (CRBD), characterized by urinary urgency, frequency, and suprapubic pain, is a clinically significant complication following transurethral resection of the prostate (TURP). Current CRBD pharmacotherapy faces inherent limitations due to adverse effect profiles. Transcutaneous tibial nerve stimulation (TTNS), a noninvasive neuromodulation therapy with demonstrated efficacy in bladder dysfunction management, shows particular promise as a safe and effective alternative for CRBD treatment. METHODS: This prospective, randomized, double-blind, placebo-controlled clinical trial enrolled patients undergoing TURP under general anesthesia. Participants were randomly allocated in a 1:1 ratio to either active TTNS intervention or sham stimulation. The primary outcome focused on CRBD-related discomfort severity assessed via the Numeric Rating Scale (NRS) immediately post-intervention. Secondary outcomes comprised CRBD severity and pain scores at 1-, 2-, and 6-h post-intervention intervals, analgesic consumption, patient satisfaction ratings, and occurrence of postoperative delirium. DISCUSSION: This protocol evaluates the therapeutic potential of TTNS for CRBD following TURP, exploring its viability as a non-invasive alternative to current CRBD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400088488. Registered on 20th August 2024.
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