Journal Article

Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis

Zytaruk, Nicole, Muscedere, John, Matic, Karlo, Deane, Adam, Arabi, Yaseen, Knowles, Serena, Heels-Ansdell, Diane, Dennis, Brittany, Thabane, Lehana, Marshall, John, Myburgh, John, Poole, Alexis, Guyatt, Gordon, Lauzier, François, Hardie, Miranda, Saunders, Lois, English, Shane, Xie, Feng, Ostermann, Marlies, Hall, Richard, Mumtaz, Hassan, Finfer, Simon, Al Fares, Abdulrahman, Venkatesh, Bala, Hammond, Naomi, Alhazzani, Waleed, Rajbhandari, Dorrilyn, Cook, Deborah

2024

Overview

Background During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective To describe the conduct of an international randomized trial of stress ulcer prophylaxis ( R e- Ev aluating the I nhibition of S tress E rosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. Methods REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. Results The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p  < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p  = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p  < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. Conclusion Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Anti-Ulcer Agents - administration & dosage / Anti-Ulcer Agents - therapeutic use / Canada / Care and treatment / Clinical Protocols / Clinical trials / COVID-19 / COVID-19 - epidemiology / COVID-19 - prevention & control / COVID-19 Pandemic / Critically ill / Data collection / Data entry / Disease prevention / Epidemics / Female / Forecasts and trends / Gastrointestinal bleeding / Gastrointestinal Hemorrhage - prevention & control / Health aspects / Health Sciences / Hospital patients / Hospital transfers / Humans / Influence / Informed consent / Intensive Care Units - statistics & numerical data / Male / Medicine / Medicine & Public Health / Methods / Middle Aged / Mortality / Pandemics / Pandemics - prevention & control / Pantoprazole / Pantoprazole - therapeutic use / Participation / Patient outcomes / Patients / Prevention / Randomization / Research ethics / Respiration, Artificial - statistics & numerical data / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Statistical Theory and Methods / Statistics for Life Sciences / Stress ulceration / Theory of Medicine/Bioethics / Ulcers / Ventilators