Academic medical careers remain marked by persistent gender inequalities, despite the growing feminisation of the medical workforce. The objective of this study was to examine whether gender differences exist in key individual and institutional determinants of academic medical career aspirations among medical residents, including research motivation, mentoring, work centrality, self-efficacy, perceived discrimination and stress.

This was a national cross-sectional online survey.

Multicentre study conducted across 36 medical schools in France.

A total of 1570 medical residents (997 women and 573 men) voluntarily participated between November 2022 and February 2023. All participants completed validated self-report questionnaires. There were no exclusion criteria beyond being enrolled in a French residency programme.

Attitudes towards research (interest, motivation, significance) were measured using the Scale of Attitudes towards Research. Mentoring was assessed with the Mentor–Mentee Perception Questionnaire, work centrality with Hirschfeld and Feild’s scale, self-efficacy with the General Self-Efficacy Scale, perceived discrimination with the Sexual Harassment and Discrimination Experiences of Academic Medical Faculty instrument and stress with the Perceived Stress Scale. Gender differences were analysed using t-tests or ² tests with Holm-Bonferroni corrections for multiple comparisons.

Compared with men, women reported lower research motivation (mean (SD) 21.0 (5.5) vs 22.8 (5.5); p_adj=0.011), lower research interest (27.1 (5.5) vs 28.1 (5.7); p_adj=0.011), lower work centrality (26.7 (7.0) vs 28.2 (8.1); p_adj=0.011) and lower self-efficacy (28.3 (5.2) vs 29.9 (5.0); p_adj=0.011). Women were less likely to report having a mentor (38.5% vs 44.5%; p_adj=0.02). They also reported substantially higher levels of experienced gender discrimination (22.8% vs 3.8%; p_adj=0.005), sexual harassment (57.7% vs 18.2%; p_adj=0.005) and perceived stress (8.48 (3.29) vs 7.27 (3.43); p_adj=0.011)

Gender differences were observed across several individual and institutional factors associated with academic medical career aspirations. Reduced access to mentoring and greater exposure to discrimination and stress among women may contribute to lower research motivation and self-efficacy. These findings highlight the need for institutional strategies addressing mentoring, workplace culture and equity to support gender parity in academic medicine.

OSF preregistration for this study is available at https://osf.io/9yseq/?view_only=1c72743f542b402ba67beed6908e597d

We designed the Optimising Care in Critically Ill at the UCHealth by Liberalising the Target O₂ in Mechanically ventilated intensive care unit (ICU) Patients to determine the effectiveness of a multimodal educational and electronic health record order panel intervention in limiting occult hypoxaemia and hyperoxaemia in patients receiving invasive mechanical ventilation by targeting a prespecified oxygen saturation (S_pO₂ 90%–96%) range.

This trial is a pragmatic electronic health record-embedded, multisite, cluster-randomised, stepped-wedge implementation of a multimodal educational and electronic health record order panel intervention aimed at achieving a standardised intermediate target range of S_pO₂ (90%–96%) or partial pressure of oxygen (P_aO₂ 60–100 mm Hg) in mechanically ventilated adult patients admitted to the ICU across a 10 hospital health system that includes a large academic centre and smaller community hospitals.

The primary endpoint is ventilator-free days to day 30, defined as the number of days alive and not receiving support through invasive mechanical ventilation following the first initiation of invasive mechanical ventilation in a participating ICU during the hospitalisation. Secondary outcomes include a variety of clinical endpoints: hospital-free days to day 30, all-cause mortality to day 90, need for supplemental oxygen at discharge and incidence of occult hypoxaemia and hypoxaemia. We will analyse primary and secondary endpoints using a mixed effects modelling framework, with specific distributions chosen depending on the type of outcome (eg, binary, count, ordinal, time-to-event).

Research is performed under a waiver of informed consent for minimal-risk research, as approved by Colorado Multiple Institutional Review Board (24-0065). Results will be disseminated in peer-reviewed publications and at national and international conferences.

NCT06501118.

To evaluate the effectiveness of early administration of excitatory amino acid (EAA) inhibitors on long-term neurological outcomes in adults with acute moderate to severe traumatic brain injury (TBI).

Systematic review and meta-analysis of randomised controlled trials (RCTs).

MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov from inception to January 2026.

RCTs comparing EAA inhibitors with placebo, standard care or any other interventions were included. Trials enrolled adult patients (≥18 years) with moderate to severe TBI (Glasgow Coma Scale score ≤12) receiving the intervention within the acute phase of care (first week).

Pairs of reviewers independently screened trials, extracted data, assessed the risk of bias (RoB) with the Cochrane RoB tool 2 and graded the certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Random effects models were used for all effect measures and trial sequential analyses (TSA) were performed for each outcome.

The primary outcome was long-term neurological function at 6 months (or the nearest earlier time point), assessed with the Glasgow Outcome Scale (GOS) or extended version (GOS-E), using the classical definitions of an unfavourable outcome (GOS 1–3 or GOS-E 1–4).

28 trials enrolling 4238 patients were included. Early administration of EAA inhibitors was not associated with reduced unfavourable neurological outcomes (relative risk 0.93 (95% CI (0.84 to 1.03); I²=40%; 15 trials, n=3613, moderate certainty). No statistically significant difference was observed based on EAA inhibitor type, timing or duration of administration, RoB or TBI severity. Mortality, intensive care unit lengths of stay and mean intracranial pressure were not statistically different between groups, but hospital length of stay was reduced in the EAA inhibitors group. The early use of EAA inhibitors was not associated with adverse events (low certainty). TSA showed insufficient power for the primary outcome.

In adults with moderate to severe TBI, the early administration of EAA inhibitors was not associated with a reduction of unfavourable neurological outcomes. Further high-quality and adequately powered RCTs are required to clarify their role in TBI management.

CRD42025635527.

To identify the factors associated with low psychological resilience among university students in the Grand Est region of France at the end of the first national COVID-19 lockdown.

A cross-sectional online survey was conducted (May 2020) among students at the University of Lorraine using the LimeSurvey platform and institutional mailing lists.

Higher education setting in north-eastern France, involving students from the University of Lorraine (multicampus public university) and Sciences Po Nancy, a political science institute in the same region.

A total of 3708 students fully completed the online questionnaire, including the Brief Resilience Scale (BRS), resulting in an estimated response rate of 7.1%. All students enrolled at the University of Lorraine and Sciences Po Nancy during the 2019–2020 academic year were eligible to participate.

The primary outcome was psychological resilience, measured using the BRS. Secondary measures included perceived social support assessed with the Multidimensional Scale of Perceived Social Support, quality of interpersonal relationships evaluated using the Quality of Interpersonal Relationships Scale (Échelle de la Qualité des Relations Interpersonnelles, EQRI) and frequency of positive and negative thoughts measured with the Thermometer of Thoughts Tool. Factors associated with low resilience were analysed using bivariable and multivariable logistic regression.

Among 3708 students included in the sample, corresponding to a response rate of approximately 7.1%, 50.6% had normal resilience, while 37.3% reported low resilience. Female gender (OR=2.1, 95% CI: 1.8 to 2.6) and low social support (OR=1.7, 95% CI: 1.1 to 2.6) were the factors associated most strongly with low resilience. Negative thoughts (OR=1.4, 95% CI: 1.4 to 1.5), lower quality of relationships with people in general (OR=1.5, 95% CI: 1.3 to 1.8) and studying arts, humanities or languages (OR=1.4, 95% CI: 1.0 to 1.8) were identified as factors associated with low resilience. Increased age (OR=0.9, 95% CI: 0.9 to 1.0) and flat sharing (OR=0.6, 95% CI: 0.4 to 0.9) were inversely associated with low resilience levels.

Resilience seems to be impacted primarily by internal and micro-environmental factors. Consolidating levels of individual resilience of at-risk populations by acting on these factors could be the key to improving their mental health.

Acute respiratory distress syndrome (ARDS) is a major public health problem, accounting for 23% of intubated patients and associated with high mortality rates. Although lifesaving, invasive mechanical ventilation can worsen lung injury when ventilator settings are poorly adjusted to lung physiology. We hypothesise that individualising ventilator settings via (1) the bedside assessment of lung recruitability using a one-breath derecruitment manoeuvre and measurement of airway opening pressure to set positive end-expiratory pressure (PEEP), (2) controlling the distending pressure and (3) controlling respiratory drive improves ARDS outcomes.

The CAreful Ventilation In ARDS trial is an investigator-led multicentre (33 centres in eight countries), open-label, randomised controlled basket trial comparing two ventilation strategies in two subpopulations of moderate-to-severe ARDS: induced or not by COVID-19. A total of 740 patients will be randomised (370 in each substudy) in a 1:1 ratio to individualised ventilator settings or to using traditional PEEP to inspired fraction of oxygen tables for PEEP setting. Indications for proning and weaning strategies are similar in both arms. The primary outcome is all-cause mortality at day 60. Secondary outcomes include duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital stay, organ dysfunction, barotrauma and mortality in ICU, at day 28 and in hospital.

Ethics approval has been obtained for all participating centres: Unity Health Toronto Research Ethics Board (for three centres: St Michael’s Hospital, Toronto General Hospital and Toronto Western Hospital); Comité de Ética de Investigación con Medicamentos del Hospital Universitari Vall d’Hebron; Comité de protection des personnes Ile de France III; Comité d'Ética de la Investigatción con Medicamentos de la Fundació de Gestió Sanitària del Hospital de la Santa Creu i Sant Pau; Comitato Etico—Fondazione Policlinico Gemelli; Comitato Etico di Area Vasta Emilia Centro; NYU Langone Health Institutional Review Board; Comité Ético Científico de Ciencias de la Salud; Il Comitato Etico Area 1 dell’Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’ di Foggia; HIGA ‘Eva Perón’ Comité de Bioética; Comité de Revisión Institucional del Hospital Británico Comité de Ética en Investigación; Complejo Médico Churruca-Visca Comité de Ética Biomédica; Comité de Ética SATI Comité de Ética en Investigación; Comité de Ética en Investigación del CEMIC; Comité de Ética SATI Comité de Ética en Investigación; Medical Research Ethics Committees United. Findings will be disseminated in peer review journals and conference presentations.

NCT03963622.

To date, few studies have investigated the factors associated with musculoskeletal patients’ willingness to donate biological samples and their knowledge regarding the use of such samples. We investigated the associations between these distinct knowledge factors, patients’ willingness to donate and socio-demographic factors.

Cross-sectional survey.

Musculoskeletal outpatient clinics across four sites in England, representing varied demographic populations.

A total of 469 adult patients attending musculoskeletal appointments were recruited through convenience sampling.

Ordinal regression models were employed to identify socio-demographic and clinical predictors of patients’ willingness to donate biological samples. Other outcome measures specifically in two areas of patient knowledge include: (1) knowledge of sample use and (2) knowledge of surgical waste tissue value and management.

Only 37% of participants were aware of the term ‘biobank’. Despite this, participants showed a high level of knowledge regarding both biological sample use and surgical waste tissue management, although their understanding varied considerably by ethnicity and education. Participants with no formal education exhibited a lower level of knowledge in both areas related to sample use and surgical waste tissue management for biomedical research ((OR 0.30, 95% CI 0.14 to 0.61; p=0.001); (OR=0.29, 95% CI 0.16 to 0.52, p

Despite low awareness, musculoskeletal patients showed a high willingness to participate in biobanking. However, significant disparities by ethnicity and education persist. Targeted, inclusive engagement strategies are needed to address under-representation and foster informed, equitable participation of musculoskeletal patients in biomedical research.

The Optimising older People’s Transition from acute care Into residential aged care through Multidisciplinary Assessment and Liaison (OPTIMAL) trial is a multisite hybrid type II stepped wedge randomised controlled trial with an embedded process evaluation that aims to evaluate the effectiveness of implementing a bundle of evidence-based interventions to provide systematic support to older adults being discharged from hospital to residential aged care (RAC) homes for the first time. The trial is based on evidence from models of care used internationally to improve the quality of care transitions and addresses a need to provide evidence of transferability and effectiveness of these models in the Australian context. The embedded process evaluation will assess the acceptability, appropriateness, feasibility, adoption and fidelity of the OPTIMAL intervention, as well as the mechanisms of impact.

The OPTIMAL trial will be implemented across the three metropolitan local health networks (LHNs) in South Australia. The process evaluation will be conducted in parallel with the main trial and is theoretically informed by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) implementation framework, which theorises that the implementation success of OPTIMAL is determined by the facilitation of the intervention with the intended recipients in their inner and outer contextual setting. The process evaluation will employ a mixed methods approach. Qualitative and quantitative data will be collected through baseline context mapping of LHNs, interviews with key LHN and RAC stakeholders, online survey of clinical teams, fortnightly check-in forms, and activity logs and field notes maintained by the nurse facilitator in each LHN. Data will be mapped and reported based on the i-PARIHS framework.

Ethical approval for the OPTIMAL trial was obtained from the Southern Adelaide Clinical Human Research Ethics Committee (approval 2023/HRE00111), and the relevant governance approvals were obtained for each participating LHN. Ethical approval includes a waiver of the requirement for consent for routinely collected patient data. Study findings will be disseminated via journal publications, presentations at conferences, stakeholder discussions, consumer forums and advocacy to key decision makers to support knowledge translation.

Australia New Zealand Clinical Trial Registry, ACTRN12624001008516, registered 20 August 2024.

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%–39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%–70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD.

This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5x10⁷ and 10x10⁷ cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%.

The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 – Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels.

NCT06636032.

The results will be disseminated through conventional scientific channels.

Stroke volume is a major determinant of tissue perfusion and, therefore, a key parameter to monitor in patients with haemodynamic instability and hypoperfusion. Left ventricular outflow tract (LVOT) velocity-time integral (VTI) measurement using pulsed-wave Doppler is widely used as an estimation of stroke volume and should be a competence required for every intensive care unit (ICU) physician. Artificial intelligence (AI) applied to ultrasound facilitates the acquisition of adequate images. The aim of the present study is to evaluate the interchangeability of LVOT VTI measurements obtained by minimally trained operators and expert physicians, both guided by AI.

This is a prospective multicentre randomised controlled trial. ICU patients in whom fluid administration is considered necessary will be included. A minimally trained operator and an expert will independently measure LVOT VTI, guided by the UltraSight AI software to obtain the best five-chamber view, before and after a 250 mL fluid challenge. The order of acquisition between each operator will be randomised. 100 patients will be included.

The primary endpoint is the relative difference in LVOT VTI between operators. Secondary outcomes include the concordance of the therapeutic decision made by the blinded physician in charge of the patient based on the measures obtained by each operator, and the agreement between absolute values of LVOT VTI obtained by minimally trained and expert operators.

The study has been reviewed and approved by a regional ethics committee (Comité de Protection des Personnes—Ile de France II—n°24.00671.000291). An information note will be given to the participant before he or she participates in the study. The present study will be disseminated through peer-reviewed publications and academic and medical conferences.

NCT06486467.

Sexual and reproductive health (SRH) for adolescents is a global public health concern. Access to SRH information and services regarding contraception is necessary, particularly in underserved regions, such as the French overseas territories of Reunion Island and Guadeloupe, where indicators for teenage pregnancy and abortion are significantly high. This study protocol describes the methodology to be used to assess the feasibility of a peer-led contraception education programme for high school students using social media.

A multicentre, exploratory sequential mixed-methods with a pre-post design, prospective study is being conducted in Guadeloupe and on Reunion Island. The qualitative component started on 31 May 2025, and the study will continue until 30 June 2026. Participants will be aged 15 to 19 years and will attend high school. In Phase 1, focus groups will explore the adolescents’ perceptions of peer influencers in contraceptive education and their suggestions for organising a prevention programme on social media. These findings will directly inform the intervention in Phase 3. At this stage of this phase, peer influencers will also be identified. Phase 2 will train selected peer educators in SHR, digital content creation to prepare them for intervention design and delivery. Phase 3 consists of the co-construction, implementation and evaluation of the intervention. Outcomes will include feasibility, acceptability, adoption, fidelity and exploratory effectiveness. The primary outcome will be peer engagement defined as the completion of at least 70% of the planned educational tasks.

This study has received ethical approval from the Comité de Protection des Personnes under RIPH3 (ID-RCB: 2025-A00358-41) and will follow the French ethical standards for low-intervention research. Results will be shared in scientific publications and with participating schools.

NCT06943209.

Giant cell arteritis (GCA) is a large-vessel vasculitis occurring in people aged over 50 years. Recent studies have shown that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, is remarkably effective in treating GCA and allows significant dose sparing of glucocorticoids. However, it makes it difficult to monitor disease activity. Furthermore, treatment is often prolonged over 1 year due to the fear of relapse after stopping TCZ and/or the absence of an optimal discontinuation scheme.

This study aims at comparing two discontinuation regimens in a population of GCA patients who have been treated with TCZ for 12–36 months and have discontinued glucocorticoids for at least 12 weeks. Patients will be randomised with a 1:1 ratio between two arms: immediate discontinuation (cessation) versus gradual discontinuation of TCZ (162 mg subcutaneously every 2 weeks for 12 weeks and then every 4 weeks for 12 additional weeks). Patients will be followed up for 78 weeks. The primary endpoint is relapse-free survival after 26 weeks of follow-up. A total of 120 patients will be randomised (60 in each group) for a period of 3 years.

The trial was approved by an independent ethics committee (CPP Sud Ouest et Outre Mer IV) and the French health authority (French National Agency for Medicines and Health Products Safety—ANSM) through the Clinical Trials Information System (CTIS) provided by the European Medicines Agency (EMA). The informed consent complies with the ICH GCP guideline and regulatory requirements. Eligible patients may only be included in the study after providing informed consent. Findings will be published in peer-reviewed journals and conference presentations.

NCT06037460.

Nipah virus (NiV) is a bat-transmitted paramyxovirus causing recurrent, high-mortality outbreaks in South and South-East Asia. As a WHO priority pathogen, efforts are underway to develop therapies like monoclonal antibodies and small-molecule antivirals, which require evaluation in clinical trials. However, trial design is challenging due to limited understanding of NiV’s clinical characteristics. Given the rarity of NiV infections, strategies targeting improved outcomes for the broader acute encephalitis syndrome (AES) patient population, including those with NiV, are essential for advancing therapeutic research. To address these gaps, we designed the Bangladesh AES cohort study to characterise the patient population, clinical features, treatment practices, common aetiologies and outcomes in patients presenting with AES, including NiV infection, as a clinical characterisation study to inform the design of clinical trials for NiV and AES more broadly.

This prospective cohort study will be conducted in Bangladesh, a NiV endemic country with annual outbreaks. In collaboration with the ongoing NiV surveillance programme in Bangladesh, we aim to enrol up to 2000 patients of all ages presenting with AES at three tertiary care hospitals within the Nipah belt. Patients who provide informed consent to participate will be monitored throughout their hospital stay until 90 days post enrolment. Data will be systematically collected through interviews and medical record reviews at several time points: on the day of enrolment, day 3, day 7, the day of critical care admission (if applicable), discharge day and 90 days post enrollment. Additionally, a portion of the cerebrospinal fluid collected under the concurrent NiV surveillance protocol will be tested for an array of viral and bacterial pathogens responsible for encephalitis at the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory.

The study received ethical approval from the Oxford Tropical Research Ethics Committee, University of Oxford, UK (OxTREC Ref: 576–23) and the institutional review board of icddr,b, Bangladesh (icddr,b protocol number: 24016). By characterising the AES patient population, this study will generate essential evidence on key clinical parameters, which will be pivotal in optimising the design of clinical trials for potential interventions aimed at improving outcomes in patients with AES, including those with NiV disease. Findings will be shared with participating hospitals, patients and relevant government stakeholders. Results will also be disseminated through conference presentations and peer-reviewed publications.

Not applicable (this is an observational study).

There is high interest in long-acting injectable antiretroviral therapy (LAI-ART) among people with HIV (PWH), with many conveniences for uptake and persistence. However, both patients and clinicians have expressed important barriers to effective implementation, including concerns about frequent clinic visits and strain on clinic resources. Administration of LAI-ART by a trained layperson injector (such as family, friend or partner of the patient) can help mitigate some of these patient-identified and clinician-identified barriers. Alternative LAI-ART delivery methods have the potential to increase the PWH and layperson injector’s confidence, empowerment, convenience, privacy and self-management skills and ultimately facilitate LAI-ART uptake and persistence.

INVITE-Home (innovative administration of long-acting injectables for HIV treatment enhancement at home) will support the expansion of LAI-ART in non-clinical settings by developing, implementing and evaluating a comprehensive, theory-informed training to support the administration of LAI-ART by a trained layperson injector. First, INVITE-Home will design and develop an innovative, theory-based layperson injector training to improve acceptability and uptake of LAI-ART in home-based settings, grounded in qualitative evaluation of training barriers and needs of PWH, layperson injectors and clinicians to develop the training. In Aim 2, INVITE-Home will enhance understanding of home-based LAI-ART using the training, by examining implementation and effectiveness of home-based LAI-ART injections.

This study and its protocols have been approved by the University of California, San Francisco (UCSF) Institutional Review Board and the scientific staff of HIV Research Branch, Division of HIV Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, at the Centers for Disease Control and Prevention. Study staff will disseminate findings locally (eg, to partnering clinics, via the UCSF Center for AIDS Prevention Studies’ Community Engagement Core), statewide (eg, the California Department of Public Health’s Office of AIDS) and nationally at conferences related to HIV.

NCT06488846.

In the intensive care unit (ICU), brain-injured patients are frequently exposed to mechanical ventilation to protect the brain and preserve physiology. After intracranial pressure control and sedation withdrawal, this population is prone to residual disorder of consciousness and altered neurological control of respiratory drive, cough and airway protection. Consequently, extubation failure is more frequent than in general ICU patients, and there is no clear evidence-based clinical trigger for extubation. Different risk factors for extubation failure were described in observational trials, and clinical scores were constructed to detect patients at higher risk of extubation failure. Nevertheless, none of these scores were prospectively tested as interventional tools to prevent extubation failure. The Brain-Injured Patients Extubation Readiness (BIPER) study is an ongoing multicentre stepped-wedge cluster-randomised controlled trial aiming to test one of these scores as an intervention protocol to decrease extubation failure in neurocritical care patients with residual disorder of consciousness.

Trial design: Stepped-wedge cluster-randomised controlled trial with five groups of three to six clusters (20 ICUs). Groups of clusters are randomised to five possible sequences of nine periods with crossing from a control condition period (usual care for extubation) to an intervention condition period (BIPER-guided extubation protocol), separated by a 3-month transition period.

Participants: Participants are clinically stable brain-injured patients (18–75 years old), requiring more than 48 hours of invasive mechanical ventilation with residual disorder of consciousness after sedation withdrawal, and who achieved a spontaneous breathing trial.

Interventions: The control condition consists of extubation based on usual care and local practice. The intervention condition consists of extubation triggered by a clinical score evaluating deglutition, gag reflex, cough and visual tracking (Coma Recovery Scale-Revised Visual Scale).

Objective: To determine whether adoption of an extubation protocol based on a clinical score can lessen extubation failure compared with usual care in brain-injured patients with residual disorder of consciousness.

Outcome: The primary outcome measure is extubation failure, defined within 5 days following extubation. The key secondary outcome measure is time to effective extubation.

Randomisation: Clusters are allocated to sequence of treatments using random blocks randomisation. The constitution of groups of clusters was stratified according to planned recruitment of each centre.

Blinding: Investigators and outcome assessors are not blinded to condition allocation.

Number of participants: 660 patients (220 in the control condition and 440 in the intervention condition).

The BIPER trial was approved by an independent ethics committee. The study began on 9 February 2020, and 571 participants are now included. Results will be published in an international peer-reviewed medical journal. 

NCT04080440.