Background: Each day in the United States, more than 50,000 patients receive general anesthesia for major surgery. When patients undergo general anesthesia, they are placing their safety and comfort into the hands of anesthesia clinicians. In particular, the anesthesia care team’s choice of general anesthesia between total intravenous anesthesia with propofol (PROPOFOL) versus inhalational anesthesia with volatile (VOLATILE) agents may drive completely different patient experiences. Some patients report, “I woke up feeling refreshed” while others state, “I threw up for hours and was groggy for days.”
Study Population and Research Setting(s): Adult patients undergoing elective noncardiac surgery with general anesthesia will be eligible. Preplanned subgroup analyses will focus on PCORI priority populations underrepresented in research. Members of the Multicenter Perioperative Outcome Group (MPOG), including more than 50 academic and private health systems across 18 states in the United States, will serve as the clinical sites. Twelve clinical sites with geographic and academic/private diversity will recruit patients undergoing surgery. Comparators: The two active comparator groups will be PROPOFOL (total intravenous anesthesia using propofol without inhaled anesthetic) and VOLATILE (inhaled volatile anesthetic). Each technique has been in use for decades, has established safety and efficacy, has similar financial costs, is used daily at every surgery center in the United States, and is within the skillset of every anesthesia clinician. The team’s analysis of 2.6 million patients undergoing general anesthesia for elective surgery between 2016 and 2019 demonstrated 82 percent received VOLATILE anesthesia, while only 18 percent received PROPOFOL despite clinician surveys indicating 70 percent preferred PROPOFOL for their own care.
Outcomes: The primary effectiveness outcome is the patient-reported Quality of Recovery-15 score (QOR15) measured the day after surgery. QOR15 is an internationally validated scale routinely used in perioperative clinical trials to assess the domains of physical comfort, physical independence, psychological support, emotional state, and pain using 15 questions. The instrument can be completed in less than three minutes and administered in person, electronically via smartphone or tablet, or over the phone. The QOR15 measures what matters to patients beyond the physiologic and medical outcomes. The primary safety outcome will be intraoperative awareness with recall (modified Brice interview), a rare (0.1 percent) and devastating adverse event during general anesthesia, which is alleged to be more frequent during PROPOFOL despite little evidence to support the belief; it will be measured at three time points. Exploratory outcomes in a subgroup of patients will include passively collected median daily step count, daily stand hours, sleep duration on POD 7-10, via a study-provided Fitbit or Apple Watch.
Study Design: THRIVE is a multicenter, pragmatic, comparative effectiveness, patient-level randomized controlled trial. MPOG has a track record of robust EHR data integration, research collaboration, and practice change implementation; each month, more than 50 hospitals contribute 130,000 patient records using a common data model and lexicon to the MPOG DCC.
Engagement Approach: A decade of patient-centered clinical trials led by the investigators of this study inform its design. Patients have been engaged in the study design, protocol, and proposal and will continue to be involved during all phases of project planning, design, and execution.
Project Structure: The University of Michigan, Washington University (St. Louis), University of Pennsylvania, and Stanford University will lead the design and execution of the study across 12 hospitals in the United States.
Impact: The team hypothesizes that participants receiving PROPOFOL will demonstrate clinically and statistically significant improvement in quality of recovery the evening of surgery and POD 1 without an increase in intraoperative awareness with recall. By conducting the first pragmatic, large-scale, comparative effectiveness, randomized evaluation of patient experience of PROPOFOL versus VOLATILE, this study will rapidly inform and improve the care of 300 million patients undergoing surgery each year worldwide. The findings of the THRIVE trial will be readily translated into real-world practice through dissemination of evidence, and specifically through the team’s extensive national MPOG quality improvement infrastructure, which provides personalized, monthly benchmarking and feedback to 50 health systems and 4,500 individual clinicians.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.