Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.

The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.

This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.

NCT03559114.

Dyspnoea affects 10% of the general population, and 12% of hospitalised patients report experiencing dyspnoea at rest. It is a common and distressing symptom experienced by people living with chronic obstructive pulmonary disease (COPD). Neuromodulation, which uses electrical stimulation to modulate neural pathways, is a validated clinical procedure offering a potential therapeutic approach. We speculate that non-invasive transcutaneous vagus nerve stimulation (tVNS) and trigeminal transcutaneous electric nerve stimulation (TENS) could improve dyspnoea management by targeting relevant neural circuits.

We will conduct a feasibility cross-over trial in people with severe COPD and significant exertional dyspnoea referred for pulmonary rehabilitation. Patients will be recruited following the prerehabilitation assessment visit comprising a clinical evaluation and a maximal cardiopulmonary exercise testing on ergocycle. Subsequently, two study visits will be conducted within 2 weeks apart from each other. Eight participants will perform a submaximal constant work rate at 80% workload of the VO₂ max, either with cervical tVNS (n=4) or trigeminal TENS (n=4). In a cross-over design, both patient groups will undergo sham and active treatment of the neuromodulation technique in a randomly assigned order. The main outcome will be feasibility, assessed by the percentage of patients who attend all visits and complete all tests. Secondary outcomes include other feasibility endpoints, the acceptability and suitability of the interventions (including an evaluation of sham as an exploratory outcome), and the incidence of adverse or undesirable events related to the procedures. Exploratory outcomes include changes in dyspnoea symptoms, measured using standardised questionnaires, such as Borg scale and the Visual Analogue Scale.

The protocol is approved by the institutional research ethics committee of the Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Estrie—CHUS, Sherbrooke, Quebec, Canada (#2025-5604) and follows 2013 Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Results will be communicated in international meetings and submitted to peer-reviewed journals with respect to the 2010 CONsolidated Standards Of Reporting Trials (CONSORT) statement for feasibility studies.

NCT06985628.