Inhaled anaesthetics can be used in mechanically ventilated critically ill patients to provide sedation. This approach to sedation potentially improves patient and health system outcomes, but further supportive evidence is needed. The objective of the SAVE-ICU clinical trial is to compare the effectiveness of inhaled versus intravenous sedation in ventilated adults with acute hypoxaemic respiratory failure.

SAVE-ICU is a multicentre, open-label, pragmatic, randomised controlled trial conducted in 15 intensive care units (ICUs) in Canada and the USA. Eligible patients include mechanically ventilated and sedated adults with acute hypoxemic respiratory failure from COVID-19 or non-COVID causes with PaO₂/F_IO₂ ratio 12 hour). A hierarchy of outcomes was identified at the time of trial design, as the trial was launched during the COVID-19 pandemic when study drug shortages, staffing challenges and healthcare system pressures were prevalent and there was a requirement for rapid evidence generation and implementation on this topic. The primary outcome and highest in the hierarchy is hospital mortality (requiring 758 participants). Secondary and lower hierarchical outcomes are ventilator-free days at day 30 (200 patients), quality of life at 3 months (144 participants) and ICU-free days at day 30 (128 participants). Additional secondary outcomes include median daily oxygenation at day 3 (PaO₂/F_IO₂ ratio), need for adjunctive acute respiratory distress syndrome therapies (prone positioning, inhaled nitric oxide, paralysis with a neuromuscular blocking agent and extracorporeal membrane oxygenation) during ICU stay, days alive and free from delirium and coma at day 14, hospital-free days at day 60 and disability score at 3 months and 12 months after enrolment.

The protocol was approved by all hospital ethics committees and by Health Canada. Informed consent will be obtained from substitute decision makers or deferred consent (as permitted by site ethics board). Trial findings will be shared at the end of the study using peer-review publications, conference presentations and social media as part of the trial knowledge translation plan.

NCT04415060.

Endometriosis is a chronic condition affecting up to 11% of people presumed female at birth by the age of 44 years, characterised by the growth of tissue similar to the lining of the uterus on other organs. Endometriosis significantly impacts health-related quality of life (HRQoL) and imposes a substantial burden on both individuals and the healthcare system. International guidelines recommend the interdisciplinary management of endometriosis due to its significant biopsychosocial burden; however, research aimed at exploring psychological approaches for endometriosis is limited. This trial aims to evaluate the effectiveness of CodeEndo, an online co-designed interdisciplinary supportive care program, compared with a waitlist control (WLC), on HRQoL and biopsychosocial outcomes in people with a diagnosis of endometriosis.

A hybrid type 1 effectiveness and implementation randomised controlled trial (RCT) will be conducted. Eligible participants will be randomly allocated to either the CodeEndo program (n=176) or WLC group (n=176) for 8 weeks. The primary outcome will be HRQoL, and secondary outcomes will include psychological symptoms (anxiety, depression, stress), self-efficacy, menstrual, bladder and gastrointestinal symptoms, pain, fatigue, sleep, exercise, diet, symptom bothersomeness and physical and psychological well-being, measured at 8 weeks post-randomisation (T2) and 6-month follow-up (T3). Cost-effectiveness will also be examined. Longitudinal qualitative individual interviews (up to n=40) will be conducted with participants who complete the CodeEndo program to explore benefits, barriers and facilitators of ongoing use. Additionally, the CodeEndo program will undergo evaluation by a group of endometriosis healthcare providers, who will assess potential barriers and facilitators to its real-world implementation. Various process evaluation strategies will also be measured to inform future implementation. Data analyses will incorporate mixed-effects regression models on an intention-to-treat basis, cost-consequences and cost-utility, dietary and qualitative thematic analysis.

This protocol received ethics approval from Deakin University Research Ethics Committee (DUREC Ref: 2024-157). Dissemination is expected to include peer-reviewed journal articles, reports, conference presentations as well as websites or social media platforms of relevant chronic pain organisations. Participants will be sent a summary of trial results.

ACTRN12623000598684p.