MPOG-Based Pragmatic Clinical Trials
Updates – THRIVE, VEGA-2, and IntraOp Ox
Allison Janda, MD
Assistant Professor, Department of Anesthesiology, University of Michigan
MPOG Retreat - October 16, 2026
Disclosures
• No personal consulting, financial, or board membership with any company
• I am a PI or Co-I on projects that receives or has recently received grant funding from:
– PCORI
– NIH
– NHLBI K23 - K23HL166685
– National Library of Medicine - 1R01LM01389401
– NIDDK - R01DK139484, R01DK13322601
– NHLBI - R01HL167790
– NIH NIGMS T32 Research Fellowship Grant – 5T32GM103730-07 (concluded)
– Haisco-USA Pharmaceuticals, Inc. (unrelated to this talk)
– Bio Intellisense, Inc. (unrelated to this talk)
Ongoing MPOG P ragmatic
Clinical Trials
But first, P ragmatic Clinical Trials?
• Pragmatic vs. Explanatory trials
• Pragmatic trials are designed to
compare an intervention in a real-
world (or near real-world) setting
• Can utilize embedded strategies
for data collection
• More applicable and generalizable
to “real-world” healthcare and
patients
https://rethinkingclinicaltrials.org/
Evidence Gaps
• Wide variation in practice continues
• Surveys demonstrate lack of compelling evidence
• Lack of generalizability in many “standard” RCTs
• Assumptions regarding ideal clinical state in standard trials
• “Efficacy” vs. “comparative effectiveness”
Pragmatic Trial Considerations
• Is the question suitable and does it matter?
– Must have clinical and cultural equipoise
• Choosing an appropriate design
• Individual vs. waiver of consent
• Site recruitment can be arduous
• Challenge to inform and educate about the
study and the protocol
• Engagement from clinical and research
champions is key
• Embedded (or at least cooperative) data
systems are needed
“If you want me to provide evidence-based
practice, start building practice-based evidence”
- Dr. Tremper
24 Centers
24 Participating Institutions
Your patient is participating in the Trajectories of Recovery after
Intravenous Propofol vs inhaled VolatilE anesthesia
(THRIVE) feasibility trial
• Administer Propofol TIVA
• Administer opioids and all other
IV agents as you deem clinically
appropriate
• Do NOT administer Inhaled Volatile
Agents (desflurane, sevoflurane,
isoflurane)
• Do NOT administer Nitrous Oxide
Your patient is randomized to receive:
PROPOFOL TIVA
DO DON’T
**remember that patients are blinded to treatment group**
Department of Anesthesiology
• Administer Inhaled Anesthetics (desflurane,
sevoflurane, isoflurane), at least 0.5 MAC
• Administer opioids and all other IV agents as you
deem clinically appropriate
Your patient is randomized to receive:
INHALED ANESTHESIA
DO
**remember that patients are blinded to treatment group**
Department of Anesthesiology
Your patient is participating in the Trajectories of Recovery after
Intravenous Propofol vs inhaled VolatilE anesthesia
(THRIVE) feasibility trial
THRIVE Trial Status
• Enrolled >12,000 patients (out of 13,000!)
• 24 participating institutions
• Outstanding adherence to TIVA and inhaled interventions
– TIVA Intervention adherence: 98.3%
– INVA Intervention adherence: 99.8%
• Excellent data completion for primary outcomes measures
– 97% for POD1 QOR-15 survey
– 99% for POD1 or POD30 modified Brice
• On track to complete recruitment EARLY in Spring of 2027
Educational Resources - https://tiva-model.org
The choice of vasopressor to prevent postoperative acute kidney
injury after major non-cardiac surgery: a multicenter pragmatic
cluster cross-over randomized trial
• NIH-funded 10-center pragmatic cluster cross-over randomized trial
• Compares phenylephrine to norepinephrine
• Primary outcome: Acute Kidney Injury
Trial
Cluster Randomized PCTs
Slide Credit: Douglas Colquhoun, University of Michigan
VEGA-2 Trial Status
• Adherence estimates are outstanding
• >88% “vasopressor of the month” adherence across
active sites
• >27,000 patients included
• 86 / 120 center*months completed
• Last pair of sites went “live” May 2026
• UCSF
• U of Mich
• UVA
• U of Maryland
• Wake Forest
• Intervention period will continue through July 2027
• Duke
• UT Southwestern
• Henry Ford Detroit
• U of Washington
• UHN – U of Toronto
IntraOp Ox Trial Overview
• Analyze 30,000+ cases at 4 hospitals with IRB approved waiver of informed consent
• Each center enrolls for 18 months (6 months of each FiO
2
target group)
• Intervention: After intubation, adjust FiO
2
to one of three target ranges until
emergence begins (approximately the surgery end time), while keeping SpO
2
>93%:
– Lower range: 0.21-0.40 (target <0.30)
– Intermediate range: 0.40-0.80 (target 0.50-0.65)
– Higher range: 0.80-1.00 (target >0.90)
• Treatment key points: FiO
2
administration is at discretion of treating physicians and
providers. All other clinical care is according to provider preferences.
https://clinicaltrials.gov/study/NCT07224243
IntraOp Ox: Inclusion/Exclusion Criteria
Cases in ORs X-Y
IntraOp Ox: Primary Outcome
• Composite of organ injury or in-hospital mortality at 30 days
Acute Kidney
Injury
Myocardial
Injury
Lung Injury Stroke
In-hospital
Mortality
• After intubation, adjust FiO
2
to one of three target ranges until
emergence begins (approximately the surgery end time),
while keeping SpO
2
> 93%:
– Lower range: 0.21-0.40 (target <0.30)
– Intermediate range: 0.41-0.79 (target 0.50-0.65)
– Higher range: 0.80-1.00 (target >0.90)
• Treatment key points: FiO
2
administration is at discretion of
treating physicians and providers. All other clinical care is
according to provider preferences.
Asks for IntraOp Ox
IntraOp Ox: Epic Integration
• Intraoperative Sidebar
showing most recent FiO
2
and SpO
2
, color
coordinated:
• On Target
• In Range
• Out of Range
Your patient may be eligible for the IntraOp Ox trial and assigned to
receive intermediate FiO2 during maintenance anesthesia. Immediately
after intubation, please adjust the fresh gas flows to meet a target FiO2
0.50-0.65, but maintain SpO2 > 93%. If using End-Tidal Control, please
select 50%. Please do this until emergence.
Click here to view more information about the IntraOp Ox trial.
If you believe that this patient should be excluded from the trial, please
use this form
IntraOp Ox Trial Status
• Active at all 4 sites (Vanderbilt, Utah, Nebraska, University of Michigan)
– Final site went live 9/1/26
– All trial support tools proceeding smoothly and site engagement is outstanding
• Enrolled >19,000 patients
• 19 site-study months completed
• >90% of on-treatment minutes adherent to assigned treatment!
• Excellent separation of treatment between the three FiO2 groups
• Enrollment and adherence are consistent with or exceed projections and expectations
• Remains on track to complete recruitment February 2028
References
1. Colquhoun, Douglas A., et al. "Considerations for integration of perioperative electronic health records across institutions for research and quality improvement: the approach taken by the
Multicenter Perioperative Outcomes Group." Anesthesia and analgesia 130.5 (2020): 1133.
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PMID: 25956159
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4. Tellor Pennington BR, Colquhoun DA, Neuman MD, Politi MC, Janda AM, Spino C, Thelen-Perry S, Wu Z, Kumar SS, Gregory SH, Avidan MS, Kheterpal S; THRIVE research group.
Feasibility pilot trial fo the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial. BMJ Open. 2023 Apr
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NA, Bollini ML, Mashour GA, Hassett A, Kent CD, Vlisides PE, Avidan MS, Kheterpal S, ˠTHRIVE Research Group: Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE
anaesthesia (THRIVE) randomised controlled trial in the USA: A protocol. BMJ Open.15(9): e103836, 09/2025. PM40953862.
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Gregory SH, du Toit L, Henrichs B, Torres B, Avidan MS, Kheterpal S; THRIVE research group. Feasibility Pilot Trial for the Trajectories of Recovery after Intravenous Propofol versus Inhaled
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