Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anaesthesia (THRIVE) randomised controlled trial in the USA: A protocol

Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA. This protocol was co-created by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 13 000-patient, multicentre, patient-blinded, randomised, comparative effectiveness trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to one of two anaesthetic approaches, TIVA or INVA, using minimisation. The primary effectiveness endpoints are Quality of Recovery-15 (QOR-15) score on postoperative day (POD) 1 in patients undergoing (1) major inpatient surgery, (2) minor inpatient surgery or (3) outpatient surgery, and the primary safety endpoint is the incidence of unintended definite intraoperative awareness with recall in all patients, assessed on POD1 or POD30. Secondary endpoints include QOR-15 score on POD0, POD2 and POD7; incidence of delirium on POD0 and POD1; functional status on POD30 and POD90; health-related quality of life on POD30, POD90, POD180 and POD365; days alive and at home at POD30; patient satisfaction with anaesthesia at POD2; respiratory failure on POD0; kidney injury on POD7; all-cause mortality at POD30 and POD90; intraoperative hypotension; moderate-to-severe intraoperative movement; unplanned hospital admission after outpatient surgery in a free-standing ambulatory surgery centre setting; propofol-related infusion syndrome and malignant hyperthermia. This study is approved by the ethics board at Washington University, serving as the single Institutional Review Board for all participating sites. Recruitment began in September 2023. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. NCT05991453.