Many patients receive oral anticoagulation for reduced stroke risk in atrial fibrillation or as treatment or prevention of venous thromboembolism. Oral factor Xa inhibitors (oral FXaI, eg, apixaban, edoxaban or rivaroxaban) are commonly prescribed for this indication. Dabigatran, an oral direct thrombin inhibitor, is similarly approved. In vitro and animal model evidence suggests that dabigatran also has direct effects on Staphylococcus aureus virulence and infection. Observational data have shown that dabigatran users are less likely to develop S. aureus bacteremia (SAB), and a small randomised controlled trial showed that dabigatran has anti-S. aureus effects when compared with low molecular weight heparins during bloodstream infection. We seek to answer whether dabigatran is superior to the oral FXaIs in achieving better SAB outcomes among patients who independently require oral anticoagulation. We report the intervention-specific protocol, embedded in an adaptive platform trial.

The S. aureus Network Adaptive Platform (SNAP) trial [NCT05137119] is a pragmatic, randomised, multicentre adaptive platform trial that compares different SAB therapies for 90-day mortality rates. For this intervention (‘Dabi-SNAP’), patients receiving therapy with an oral FXaI will be randomised to continue as usual or to change to dabigatran as of the next scheduled dose. All subjects will receive standard of care antibiotics and/or antibiotics allocated through other active domains in the platform. As the choice of anticoagulant may not demonstrate large differences in mortality, a ranked composite of death and adverse outcomes (Desirability of Outcome Ranking, or DOOR) was chosen as the primary outcome.

The study is conditionally approved by the research ethics board of the McGill University Health Centre: identifier 2025-10900. Trial results will be published open access in a peer-reviewed journal and presented at a global infectious disease conference. The trial is registered at clinicaltrials.gov with the identifier NCT06650501.

NCT0665050.

There is a pressing need for effective interventions that can support healthcare workers and caregivers in the challenging yet crucial task of disclosing the HIV status to infected children and adolescents. Previously, we developed and tested a successful disclosure intervention called Sankofa in Ghana. In an ongoing 5-year follow-up study, Sankofa 2, we aim to build on the successful Sankofa trial by testing the intervention on a larger scale.

This study is a pragmatic, stepped-wedge cluster randomised trial.

It is being conducted in 12 HIV paediatric clinics in Ghana to examine the effectiveness, health benefits, cost and implementation of the Sankofa intervention. Caregiver–child dyads (n=700) will be enrolled. Evaluation of effectiveness, health benefits, cost and implementation of the Paediatric HIV disclosure intervention, Sankofa 2, is posed to offer valuable insights for scale-up and sustainability.

Ethical clearance has been obtained from the Ghana Health Service Ethics Review Committee, the University of Ghana Ethical and Protocol Review Committee, the Committee on Human Research Publication and Ethics of the Kwame Nkrumah University of Science and Technology, the Johns Hopkins Medicine Institutional Review Board and the Yale School of Medicine Human Investigation Committee. The clinical trial was registered on ClinicalTrials.gov on 5 March 2021. All caregiver participants are required to provide written informed consent and the children assent before enrolment. If either the child or caregiver says no to the study, the dyad is not eligible for the study. No study-related procedures are performed until consent is obtained. The results of the trial will be added on ClinicalTrials.gov, published in peer-reviewed journals and presented at international conferences.

NCT04791865.

Diagnosing pulmonary tuberculosis (PTB) in children is challenging owing to paucibacillary disease, non-specific symptoms and signs and challenges in microbiological confirmation. Chest X-ray (CXR) interpretation is fundamental for diagnosis and classifying disease as severe or non-severe. In adults with PTB, there is substantial evidence showing the usefulness of artificial intelligence (AI) in CXR interpretation, but very limited data exist in children.

A prospective two-stage study of children with presumed PTB in three sites (one in South Africa and two in Pakistan) will be conducted. In stage I, eligible children will be enrolled and comprehensively investigated for PTB. A CXR radiological reference standard (RRS) will be established by an expert panel of blinded radiologists. CXRs will be classified into those with findings consistent with PTB or not based on RRS. Cases will be classified as confirmed, unconfirmed or unlikely PTB according to National Institutes of Health definitions. Data from 300 confirmed and unconfirmed PTB cases and 250 unlikely PTB cases will be collected. An AI-CXR algorithm (qXR) will be used to process CXRs. The primary endpoint will be sensitivity and specificity of AI to detect confirmed and unconfirmed PTB cases (composite reference standard); a secondary endpoint will be evaluated for confirmed PTB cases (microbiological reference standard). In stage II, a multi-reader multi-case study using a cross-over design will be conducted with 16 readers and 350 CXRs to assess the usefulness of AI-assisted CXR interpretation for readers (clinicians and radiologists). The primary endpoint will be the difference in the area under the receiver operating characteristic curve of readers with and without AI assistance in correctly classifying CXRs as per RRS.

The study has been approved by a local institutional ethics committee at each site. Results will be published in academic journals and presented at conferences. Data will be made available as an open-source database.

PACTR202502517486411

Secondary and tertiary renal hyperparathyroidism (RHPT) are common sequelae of chronic kidney disease and are associated with worse patient mortality and quality of life. Clinical guidelines remain lacking with regard to recommendations for using intraoperative parathyroid hormone (IOPTH) during surgery for RHPT. A prospective randomised study will help evaluate the role of IOPTH in guiding surgery for secondary and tertiary RHPT.

Intraoperative parathyroid hormone monitoring to guide surgery in renal hyperparathyroidism is a pragmatic, multicentre, five-arm, parallel-group, patient-blinded and outcome assessor-blinded prospective pilot trial used to evaluate the feasibility of performing a definitive trial. Eligible participants include adult patients diagnosed with secondary or tertiary hyperparathyroidism who are candidates for subtotal or total parathyroidectomy. Consenting patients will be randomly assigned, through central allocation, in a 1:1:1:1:1 fashion to undergo surgery with IOPTH monitoring (four experimental arms: postexcision IOPTH samples taken at 10, 15, 20 or 25 min) or to undergo surgery without IOPTH monitoring (control arm). The primary feasibility objective is to estimate the percentage of eligible patients that are randomised: ≥70% proceed; 50–69% modify protocol before proceeding;

Ethics approval was obtained from the Hamilton Integrated Research Ethics Board. Pilot trial results will be shared widely through local, national and international academic and clinical networks and will be disseminated through conference presentations and publication in peer-reviewed journals.

NCT06542315, registered on 6 August 2024.