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.

Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

Falls are a critical problem for older people, including those from ethnically diverse communities, who are under-represented in research. The aim of this pilot trial is to evaluate (1) the implementability of a co-designed intervention developed to support the sustained uptake of tailored exercise to reduce falls (MOVE Together: Reduce Falls) and (2) the feasibility of conducting a randomised controlled trial (RCT) in older people from Italian, Arabic, Cantonese or Mandarin-speaking communities.

Investigator and assessor-blinded pilot two-arm parallel RCT. 60 older people at risk of falls from Italian, Arabic, Cantonese or Mandarin speaking communities will be recruited, with the option to enrol on their own or with another participant (dyad). Participants or dyads will be randomly assigned to the experimental or control arm. The experimental arm will receive MOVE Together: Reduce Falls, which provides up to 12 sessions with a physiotherapist over 12 months and supports participants to engage in individualised exercises. Both arms will receive educational resources in the participant’s preferred language. The primary outcome is implementability of the co-designed intervention, MOVE Together: Reduce Falls; operationalised as fidelity (>70% of intended sessions delivered), feasibility (> 95% of sessions delivered with no serious adverse events related or likely related to the intervention) and acceptability (>50% acceptability score). The secondary outcome is feasibility of the RCT protocol, which will be evaluated quantitatively (eg, recruitment and retention rates, completion of clinical outcome data including prospective collection of falls data for 12 months via falls calendars) and qualitatively (eg, barriers and enablers to data collection).

Ethical approval has been granted for this study (HREC/106010/MH-2024). Study findings will be published in peer-reviewed journals and presented at relevant conferences and community forums.

ACTRN12624000658516.

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation that is not fully reversible and is associated with an abnormal inflammatory response of lungs to noxious particles and gases. The inflammatory and reparative processes occurring in the lungs induce a ‘spill-over’ of inflammatory mediators into the circulation, resulting in an increase in systemic inflammation, which is further increased during acute exacerbations of COPD (AECOPD), leading to the development of extra-pulmonary comorbidities, such as cognitive impairment. Cognitive impairment affects up to 61% of people living with COPD. Heightened levels of inflammation have been linked to increased risk of cognitive impairments; however, the exact mechanisms remain unclear, thus hampering the development of therapeutics. This study aims to determine whether patients hospitalised with an acute COPD exacerbation show impaired cognitive function compared with recovery (~day 45), and whether such dysfunction is associated with systemic inflammation and oxidative stress.

A prospective, observational study will be conducted at Austin Health in Victoria, Australia. Eligible participants will be assessed during admission for AECOPD and following stabilisation (approximately day 45). The primary outcome is the difference in cognitive function between admission for AECOPD to recovery using non-verbal cognitive tests. Secondary outcomes are changes in systemic markers of inflammation, oxidative stress and ACE2 catalytic activity. Tertiary outcomes are anxiety and depression scores.

Ethical approval has been granted in Australia by Austin Health Human Research Ethics Committee (HREC 56099) with governance approval at Austin Hospital. The results will be published in peer-reviewed scientific journals and presented at national and international scientific conferences. Findings will be disseminated to consumers in publications for lay audiences.

SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.

CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.

The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).

NCT05614349

Micronutrient deficiencies remain prominent drivers of adverse maternal and child health outcomes in Nepal. Gender-based inequalities and norms around women’s status and access to nutrition exacerbate poor nutritional status. Many newly married, preconception women lack adequate nutrition due to delayed engagement with the health system and limited autonomy to prioritise their own health. To address this gap, the Sumadhur trial provides multiple micronutrient supplements (MMS) alongside a household-level behavioural intervention targeting newly married women, their husbands and mothers-in-law.

This will be a village-cluster randomised controlled trial across three districts in Nepal, enrolling 700 households, each comprising a triad of newly married woman, husband and mother-in-law. Villages will be randomised to receive either Sumadhur behavioural intervention+MMS (intervention) or standard of care (control). In intervention villages, participants will join weekly group sessions for 5 months, covering maternal and reproductive health, equitable household food allocation and nutrition information, and gender norms and household relationships. Women will receive three bottles of MMS (180 tablets each) over 18 months. Quantitative data collection at baseline, 6, 12 and 18 months will include surveys, venous blood draws (not at 12 months) and anthropometry. Primary outcomes will be anaemia prevalence and micronutrient status (iron, folate, vitamin B₁₂). Secondary outcomes will include reproductive behaviours, birth outcomes and intrahousehold relationship dynamics. A nested qualitative component will employ longitudinal in-depth interviews with triads to understand the mechanisms of behavioural change. Impact will be measured through an intention-to-treat approach using mixed-effects logistic regression analyses.

The study is approved by institutional review boards in the Ethics Board of the Nepal Health Research Council and the University of California, San Francisco IRB. Results will be disseminated to participating communities, local stakeholders and international audiences through workshops, peer-reviewed publications and policy briefs.

All data will be made publicly available (deidentified) after the publication of the main impact paper.

NCT06810440.

Advancing equity, diversity and inclusion in health research trials is essential for improving health outcomes among priority populations. While evidence increasingly highlights the importance of cultural diversity in research trial leadership and participation, evidence-based strategies for enhancing this remain limited. This article outlines approaches to strengthen Aboriginal and Torres Strait Islander involvement in health research trials, drawing on insights from community engagement at the Darwin (Northern Territory) trial site of the Australian Fans in Training (Aussie-FIT) project.

Community engagement at this site aimed to (1) build mutually beneficial relationships with community leaders, specifically Aboriginal and Torres Strait Islander men; (2) codesign engagement standards to enhance the quality of engagement with these leaders and more broadly with local community members and stakeholders. A culturally diverse community advisory group was established, which codesigned engagement standards tailored to community needs and preferences.

While the codesigned standards supported Aboriginal and Torres Strait Islander trial leadership and participation during the trial, the extensive consultation needed to build cross-cultural relationships and develop the standards meant they were finalised only after trial recruitment had ceased. As a result, researchers were unable to fully implement them in the early stages of the trial.

This paper shared and critically discussed approaches used in the early stages of the Aussie-FIT trial to foster more equitable and inclusive practices in research trials. Implementation of these approaches and community-informed recommendations has the potential to enhance research quality, build trust with priority populations and address participation inequities, thus supporting effective trial design and improved health outcomes.

This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000437662).