REACT SHOCK trial protocol and analysis plan—a multicenter randomised controlled trial comparing individualised blood pressure target versus standard blood pressure target among critically ill patients with shock

Background Critically ill patients with shock receiving vasopressor or inotrope therapy in ICU are often exposed to relative hypotension, which is quantified as percentage blood pressure deficit relative to usual pre-illness blood pressure. Whether minimising such blood pressure deficit, by adjusting blood pressure targets according to patients’ pre-illness blood pressure (individualised blood pressure target strategy), can improve clinical outcomes remains unclear. Therefore, we are conducting a multicenter randomised controlled trial, the REACT SHOCK RCT, comparing individualised blood pressure targets to standard care among critically ill patients with shock. Methods The REACT SHOCK RCT is an international, multicenter, parallel-group, randomised, standard-care controlled, clinical superiority trial that will be conducted in up to 35 ICUs in Australia, Ireland, Singapore, UK and USA. In total, 1260 patients, receiving vasopressor therapy for non-haemorrhagic shock in ICU, will be randomly assigned to individualised mean arterial blood pressure (MAP) targets (determined as an average of 2–5 recent pre-illness blood pressure readings within last 3 years, with a MAP target range of 55 to 95 mmHg) or standard care (default MAP target of 65 mmHg) in a 1:1 ratio. The REACT SHOCK RCT is anticipated to complete recruitment by 2028. The primary endpoint is all-cause 14-day mortality. Secondary endpoints are major adverse kidney events by day 14, all-cause 90-day mortality, survival time to 14 days and 90 days, and renal replacement therapy free days by day 28. Discussion The REACT SHOCK RCT is the first international multicenter randomised clinical trial designed to ascertain whether an individualised blood pressure target strategy is superior to standard care for critically ill patients with shock. This trial will generate evidence that may influence current recommendations for MAP targets during management of shock in ICU. The pre-specified protocol summary and statistical analysis plan are presented here. Trial registration Prospectively registered on Australian and New Zealand Clinical Trials Registry (ANZCTRN 12623000044628); ClinicalTrials.gov ID NCT05850962 dated 29th April 2023.