Acute kidney injury (AKI) is prevalent among children with severe malaria, contributing to considerable morbidity and mortality. Oxidative stress has been implicated in the pathophysiology of malaria-induced AKI, and paracetamol, with its antioxidant properties, has been proposed as a solution. This phase I/II randomized trial evaluated paracetamol as a potential renoprotective adjunct in children with severe malaria and acute kidney injury. We conducted a phase I/II open label parallel randomized controlled trial of 40 hospitalized children aged > 6months to < 12years with malaria-induced AKI in eastern Uganda. Participants were randomized by a sealed envelope 1:1 to receive either oral paracetamol 20mg/kg 6 hourly for 48h or tepid sponging every 30min until fever subsided. Only the assessors of the primary outcome were masked to the intervention. The primary outcome was renal recovery at 48h assessed using restricted mean survival time (RMST) in intention to treat population of children according to their randomization groups. Between 19 September 2021 and 25 August 2023, 250 children with hemoglobinuric severe malaria were screened and the 40 enrolled were randomly assigned paracetamol (n = 20) or tepid sponging (n = 20). The mean age was 6.54 (2.61) years. The mean time to renal recovery in the paracetamol group was 0.491h (95% CI, -9.265 to 10.248; p = 0.921) longer than the control group within 48h, but this difference was not statistically significant even after adjusting for age and weight: 1.04h (95% CI, -8.61 to 10.70; p = 0.832). The safety assessment indicated no significant differences in adverse events and hepatotoxicity in either group. Although paracetamol was safe, it did not significantly improve renal recovery in children with malaria-induced AKI. Further larger studies are needed to explore this role of paracetamol. ISRCTN84974248. Registered on August 12, 2020.

BackgroundGastric bypass surgery is an efficient surgical intervention for the treatment of obese patients. The procedure can be performed either laparoscopically or robotic assisted. To simplify the intracorporeal handling of the suture material in a bi- or tri-dimensional plane, a new generation of sutures, named barbed sutures, has been developed recently and is being used for different indications. Barbed sutures allow knotless slippage-resistant suturing due to the self-anchoring elements distributed along the thread length and therefore obviate the need for assistance. Their safety and efficacy have been demonstrated in several meta-analyses and systematic reviews. In the present study, the clinical performance of a new unidirectional barbed suture material, which differs in regard to its configuration from other barbed suture materials, is analysed and compared to a conventional suture material in robotic-assisted gastric bypass surgery to treat morbid obesity.MethodsThe study will be performed as an industry-sponsored, mono-centre, randomized, active-controlled, two-arm, parallel-group, superiority trial. A total of 150 patients will be randomly allocated to both suture types in a 1:1 ratio. The suture material will be used to construct the gastro-jejunal anastomosis as well as the jejuno-jejunal anastomosis. The time needed to create both anastomoses is the primary endpoint. Intraoperative handling of both suture materials, patient satisfaction, pain, and complications occurring during the study will serve as secondary outcomes. Furthermore, the difference in quality of life using two different questionnaires (EQ5D5L and Bariatric Analysis and Reporting Outcome System (BAROS)) will be assessed preoperatively and postoperatively (30 days and 12 months) and will be compared between the suture groups as well as over time. The EQ-5D-5L questionnaire consists of five dimensions (mobility, self-care, usual activities, pain or discomfort, anxiety or depression) and a visual analogue scale (VAS) to record the patient’s health status. The BAROS evaluates three sub-categories: The percentage of excess weight loss, the changes in medical conditions, and quality of life, leading to three individual sub-scores, which are added to the final total score defining the failure or success of treatment. The follow-up period is 1 year after surgery.DiscussionTo our knowledge, the BARGASTRO study will be the largest randomized controlled trial investigating a barbed suture versus a conventional one in robotic-assisted gastric bypass surgery to treat obese patients. The study will provide and report clinical data on evidence level Ib.Trial registrationNCT05433688. Registered on 12 Oct. 2022

BackgroundThe AAMS open-label clinical study demonstrated the safety and feasibility of epicardial transplantation of autologous right atrial appendage micrografts (AAMs) during coronary artery bypass grafting (CABG) surgery. The study also provided the first indications of therapeutic efficacy of the AAMs, as delivered within an extracellular matrix patch, to reduce ischemic scar and increase viable ventricular wall thickness. To further evaluate the initial beneficial effects observed in the AAMS study, we designed the randomized, double-blinded, and placebo-controlled AAMS2 trial. Focusing on patients with ischemic heart disease (IHD) and myocardial scar, the AAMS2 trial aims to generate state-of-the-art structural and functional imaging data of the myocardium treated with an AAMs-patch during CABG.MethodsThe AAMS2 trial recruits IHD patients who are set to undergo non-urgent CABG and present with an ischemic myocardial scar in preoperative cardiac magnetic resonance imaging (CMRI) with late gadolinium enhancement. Patients are randomized (1:1) to receive a collagen-based matrix patch (Hemopatch®), with or without AAMs, epicardially onto the scar border. The primary endpoint, assessed by CMRI preoperatively and at 6 months post-operative follow-up, focuses on the left ventricle scar mass. The secondary endpoints center on the change in scar mass by the AAMs-patch site and evaluation of therapy safety and feasibility as well as its effects on myocardial structure and function by echocardiography. Change in blood N-terminal-pro-BNP levels in the timeframe is the co-primary endpoint.DiscussionData from the AAMS2 trial provides the first randomized, blinded, and placebo-controlled evaluation of efficacy on epicardial AAMs transplantation for ischemic myocardial scar. This data will pave the road towards rational design of larger AAMs therapeutic efficacy-addressing trial(s).Trial registrationClinicalTrials.gov, NCT05632432, registered 30 November 2022, https://clinicaltrials.gov/study/NCT05632432.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-025-09379-4.

BackgroundModerate-late preterm infants born at 32–35 completed weeks’ gestation constitute a large proportion of all preterm births (< 37-week gestation), yet they are not well represented in the newborn resuscitation literature. Preterm infants often receive respiratory support in the delivery room, and recommendations exist to guide the use of supplemental oxygen when providing this support. However, there are minimal data regarding the best initial supplementary oxygen concentration for moderate-late preterm infants requiring respiratory support at birth, resulting in practice variation. The aim of this trial is to compare initial supplementary oxygen concentrations of 30% and 21% (air) in preterm infants of 32–35 weeks’ gestation who require respiratory support in the delivery room, with a primary outcome of the need for ongoing respiratory support upon leaving the delivery room.MethodsThis is a prospective, unblinded, multicenter, cluster-randomized, crossover trial in Australian maternity hospitals comparing initial supplementary oxygen concentrations of 30% and 21% (air) in moderate-late preterm infants who require respiratory support at birth. Eligible infants are those born from 32 + 0 to 35 + 6 weeks’ gestation without major cardiorespiratory or craniofacial anomalies, who are receiving active care, and who receive respiratory support in the delivery room within the first three minutes after birth. The primary outcome is the need for ongoing respiratory support upon leaving the delivery room. The trial will recruit a minimum of 1200 infants from at least 20 study sites in Australia using a waiver of consent process.DiscussionThe AIROPLANE trial is a pragmatic study in an underrepresented population using a novel study design. It will be the first randomized study of initial supplementary oxygen concentration during respiratory support in the delivery room to exclusively recruit moderate-late preterm infants. The results will address an important evidence gap and will inform future international guidelines.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12621001267842. Registered on 20th September 2021.

Participation in clinical cancer research trials should diversely reflect the intersectionality characteristics of the general population for results to be representative and applicable. European migrant populations residing in the United Kingdom (UK) are a group whose participation in clinical research warrants further exploration from a community and clinical perspective. This study aimed to explore the barriers and facilitators of individuals who have migrated to the UK from an EU8 or EU2 (EU8/2) country to participating in clinical cancer research trials to update clinical and research agendas for optimising inclusive engagement strategies. Perspectives of migrant individuals and of clinical research staff were explored to identify barriers and opportunities for optimising engagement. Five focus groups with clinical research staff at four hospitals across the East Midlands and three online focus groups with individuals who had migrated to the UK from Poland, Latvia and Romania were conducted. Data was analysed using template analysis. Twenty-two clinical research staff and 17 individuals from EU8/2 countries participated in the study. Three key themes and related subthemes were identified: (1) Ambivalence, misunderstanding and fear shape cancer research perceptions (1.1. a lack of familiarity with cancer research practices; 1.2. Cancer fear may hinder participation); (2) Structural barriers and gaps in cultural competency; and (3) Building trust through community engaged research (3.1.Co-researching with communities; 3.2.Incentivising and legitimising research). Many migrant participants were unfamiliar with UK-based research practices, and it was suggested that fatalist attitudes towards a cancer diagnosis and mistrust of research generally created apprehension and defensiveness when hearing about clinical cancer research in migrant communities. Migrant individuals and staff endorsed research design strategies which engage community champions (including clinicians); narrate positive stories of cancer research participation; and consider language accessibility and comprehension as key elements of engagement-focused research design.

IntroductionAutism spectrum disorder (ASD) affects millions of children worldwide, negatively impacting the daily functioning and quality of life of patients and their families. New therapeutic approaches for ASD are being investigated. Probiotics have shown promise in modulating gut microbiota and ameliorating ASD symptoms. We aim to evaluate the impact of a 12-week multispecies probiotic supplementation on the severity of core autism symptoms in children with ASD.Methods and analysisThis study is a randomized, double-blind, placebo-controlled clinical trial. One hundred and 10 children aged 7 to 15 years diagnosed with ASD will be randomly assigned in a 1:1 ratio to receive either a probiotic mixture or a placebo for 12 weeks. The probiotic mixture contains 5 × 109 colony-forming units per dose of Bacillus subtilis W20, Bifidobacterium infantis W17, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus rhamnosus W140, Lactococcus lactis W19, and Propionibacterium freudenreichii W200. The primary outcome will be the assessment of core autism symptoms using the Autism Symptom Rating Scales (ASRS). The secondary outcomes will include the quality of life, evaluations of sleep impairments, parental stress levels, gastrointestinal symptoms, and urinary p-cresol levels. These outcomes will be assessed twice: at baseline and after 12 weeks of intervention.Ethics and disseminationThe study has received approval from the Ethics Committee of the Medical University of Warsaw. Results will be submitted to a peer-reviewed journal and presented at national and international scientific meetings.Trial registrationNCT06448767. Registered on 3 June 2024Protocol versionVersion 2, 27 of October 2025Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-025-09373-w.

The implantation of cardiac implantable electronic devices (CIED) is the treatment of choice for the prevention of sudden cardiac deaths in high-risk patients. Given the comorbidities, this superficial surgical intervention is mostly performed in local anaesthesia. Triggered by the upcoming opioid crisis, the burden of postsurgical pain has gained popularity, as adequate perioperative pain management is a cornerstone in the prevention of persistent opioid use. Aim of this study is to assess the perioperative pain management of local anaesthesia versus pectoserratus plain/interpectoral plain (PSP/IPP) block for submuscular CIED implantation. In a single-centre, prospective, single-blinded, two-group randomized trial, 80 patients undergoing submuscular CIED implantation will be randomized to receive a PSP/IPP with ropivacaine 0.375% (intervention group) or a LA with lidocaine 2% (control group). The primary outcome is the Quality of Recovery-15 (QoR-15) assessed 24h after surgery. Secondary endpoints include the intraoperative additional LA administration; the postoperative analgesic consumption; the need and dose of additional analgesia; Visual Analogue Scale (VAS) after 2, 4, 6, 12, and 24h; and VAS-AUC and VAS groups <30mm/30-60mm/>60mm. This prospective, randomized, controlled, and single-blinded trial aims to assess if a PSP/IPP with ropivacaine affects the postoperative QoR-15 score compared to a conventional local anaesthesia with lidocaine in patients undergoing submuscular CIED implantation. Given the impressively high rate of persistent opioid use (POU) in patients after CIED, results from this study could help improve the perioperative pain management. EUDRA CT Number: 2023-508997-27. Registered on 20 September 2024. https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-508997-27-00 .

BackgroundAntibiotic resistance (ABR) is a global health threat, significantly driven by its misuse. The World Health Organization stresses the need for better antibiotic use to combat ABR through behavioral change interventions. Visual storytelling, which merges narrative with visuals, can enhance health behaviors by boosting cognitive and emotional engagement. In Pakistan, more than half of the population lack access to mobile phone, limiting digital health solutions. To address this gap, we developed a culturally tailored Visual Storytelling for Antibiotic Adherence (VISTA) intervention – a theory-driven sticker-based tool – to improve antibiotic adherence among urinary tract infection (UTI) patients in low-connectivity settings.MethodsIn this parallel, two-arm superiority randomized controlled trial, participants with physician-confirmed uncomplicated UTI who have filled an oral antibiotic prescription will be recruited from six tertiary care hospitals in Khyber Pakhtunkhwa, Pakistan. The participants will be randomized in a 1:1 manner to receive either the VISTA intervention or standard care. The VISTA intervention was developed based on nudge theory, guided by the Taxonomy of Choice Architecture framework, and complemented by the MINDSPACE (messenger, incentives, norms, defaults, salience, priming, affect, commitments, and ego) framework. It was developed and validated through a Delphi method, assessing expert feedback, and refined based on a patient understanding study. The intervention sticker uses contrasting colors—red (non-adherence: bacteria evolving into “superbugs”) and green (adherence: antibiotics fully eradicating bacteria)—to communicate the consequences of incomplete versus complete adherence. The primary outcome is adherence, measured by pill count at the initial follow-up. Secondary outcomes include UTI recurrence, knowledge, and attitudes regarding antibiotic adherence. Analysis will follow both intention-to-treat and per-protocol principles.DiscussionThis randomized controlled trial will evaluate a theory-driven, scalable intervention for low-resource, low-connectivity settings, aligning with WHO priorities for ABR mitigation. It addresses the patient support gap caused by limited digital access. Pill counts provide an objective adherence measure, though they may miss intentional non-adherence; including UTI recurrence as a secondary outcome helps mitigate this. Cultural tailoring through expert panels and patient feedback aims to enhance relevance and applicability across similar contexts, improving generalizability.Trial registrationThe trial was registered with ClinicalTrials.gov (registered: March 13, 2025, NCT06885658, https://clinicaltrials.gov/study/NCT06885658).Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-025-09328-1.

Adolescence is a period of rapid physical, psychological, and social change. Older adolescents (15-19years) experience key transitions; successfully navigating these can reduce the risk of stress and may mitigate subsequent impacts in adulthood, given that stress and depression in young people are highly correlated with behavioural risk factors such as alcohol and substance use, physical inactivity, and poor dietary behaviours. The Adolescent Resilience-Building In Urban Slums-A Multifaceted Implementation Trial of Life Skills Education in India (ANUMATI 2.0) will be undertaken in 105 slums across New Delhi and Hyderabad/Secunderabad in India among older adolescents. The hypothesis is that life skills administered either in-person or through social media will improve wellbeing, depression symptoms, and lead to a reduction in other non-communicable disease risk factors (smoking, alcohol and substance use, physical inactivity) relative to enhanced usual care. A secondary hypothesis is that the social media-based programme will be more cost-effective than the in-person programme. The Life Skills Education Programme (LSEP) was co-designed with adolescents from slums and comprises four modules delivered over 8months, with refresher sessions being carried out in the remaining 4months of the 12-month implementation period. It will be implemented and evaluated in a 3-arm, hybrid type 2 cluster randomised controlled trial with process and economic evaluations. Older adolescents will be screened for depression and suicide ideation using the Patient Health Questionnaire (PHQ-9). Adolescents with a PHQ-9 score ≥ 10 and/or a score ≥ 2 on the self-harm/suicide risk question of the PHQ-9 will be included in the trial. Arm 1 will receive the in-person LSEP, arm 2 will receive the LSEP delivered through social media platforms, and arm 3 will be provided with enhanced usual care. Life skills education is an evidence-based approach to enhance young people's resilience to stressors. It focusses on improved communication, assertiveness, self-awareness, decision-making, problem solving, and creative thinking. The findings from this study will generate evidence on scalable strategies to enhance resilience and reduce non-communicable disease risk factors for young people living in resource-limited settings both in India and elsewhere. Clinical Trial Registry India, CTRI/2024/08/072338. Registered on August 12, 2024.

The COVID-19 pandemic posed a major public health challenge with varying devastating effects on the global community. Vaccination is the most effective measure in combating this pandemic. A major challenge, especially in resource-limited settings, was the shortage of the vaccines. However, evidence by WHO in the use of fractionated doses in combating yellow fever prompted the evaluation of the safety and immunogenicity of fractionated doses of COVID-19 vaccines (ChAd0x1, AD26.COV2.S, and BNT162B2) among Nigerian adults (18-65years). This is a multi-center, non-inferiority randomized, triple-blind trial involving 1812 COVID-19 vaccine naïve participants. Six hundred four eligible participants will be randomized into each of the three vaccine arms of ChAd0x1, AD26.COV2.S, and BNT162B2 COVID-19 vaccine. 151 participants will be randomized each into the 25% and 50% fractionated dose and 300 in the standard full dose arm for the ChAd0x1 and AD26.COV2.S group. In the BNT162B2 group, 201 participants will be randomized into the 50% fractionated dose and 403 into the standard dose arms. The efficacy (immunogenicity) will be evaluated by collecting blood samples at baseline (day 0) and day 28 after immunization to determine the geometric mean fold rise (GMFR) of ≥ 2.5 within the range of 20% non-inferiority to the standard dose of anti-SARS-CoV-2 S antibody response detected by ELISA termed as seroconversion. Safety and adverse events will be evaluated through active evaluation during the first 72h of vaccine administration and on days 14 and 28 of clinic visits. The trial will also assess secondary immunogenicity variables of 50% plaque plaalite reduction neutralization by antibodies against SARS-CoV-2 variants (α, δ, and κ) and cytokines production (IFNα, γ, and IL-2 producing CD4 and CD8 T lymphocytes). The proposed trial will allow for a comprehensive understanding of the immunologic responses and safety profile of fractional doses compared to full doses of COVID-19 vaccines among Nigerian adults. In addition, this will guide policy implementation for prompt vaccination of the population to maximize access to the limited vaccines available during the COVID-19 pandemic or future epidemics/pandemics. The study is registered at the Pan African Clinical Trials Registry (PACTR), a primary registry in the WHO International Clinical Trial Platforms. PACTR202206754734018. Registered on June 1, 2022, Accessible at: https://pactr.samrc.ac.za/ Trial Sponsor: Open Philanthropy.