THRIVE: Trajectories of Recovery after
Intravenous propofol vs inhaled VolatilE
anesthesia
Sachin Kheterpal, MD, MBA
Research Director, MPOG
Outline
• Background
• Comparators and Outcomes
• Patient Population
• Study Phases
• Resources
• Projected Timeline
• One patient back to
baseline in 2 days
• Another patient takes
more than a week
Background
• Multicenter, pragmatic randomized control trial to
evaluate superiority of propofol TIVA over inhaled volatile
general anesthesia for patient experiences and outcomes
• Support from the Patient-Centered Outcomes Research
Institute (PCORI). $30M total over 6.5 years
Study overview
Patient Population
• 12,500 adult patients undergoing elective,
non-cardiac surgery (≥60 min) requiring general
anesthesia (both ambulatory and inpatient cases are
eligible)
• Exclusions for patients precluded from receiving one
of the techniques or if one technique is strongly
indicated (thyroidectomy, spine with monitoring)
What does propofol TIVA and inhaled volatile mean?
• Pragmatic definition to reflect routine care
• We have learned “routine” care varies VERY widely across clinicians and centers
• Propofol TIVA
– Propofol-based intravenous general anesthesia
– No use of inhaled (nitrous, isoflurane, sevoflurane, desflurane) at any point in surgery
– May use other intravenous adjuncts (dex, remi, sufentanil, lidocaine)
• Inhaled volatile
– Inhaled-volatile based general anesthesia
– Propofol infusion can be used
– May use other intravenous or inhaled adjuncts (nitrous,dex, remi, sufentanil, lidocaine)
• Up to the clinician
– Processed EEG monitoring
– Regional anesthesia
– ETT vs LMA
Time to put the T back in TIVA
• 80-90% of GA in MPOG are inhaled volatile based
• MIVA and DIVA don’t count
– “mostly” and “dirty” IVA
• Will require cross MPOG education and building on our QI mission,
regardless of THRIVE study
– How to deliver a TIVA in 2021 without TCI pumps
– How to use and interpret processed EEG
– Best practices to avoid intraoperative awareness
– Patient experiences after anesthesia
• Will advance patient care, regardless of THRIVE
• Anesthesia clinicians prefer TIVA 3:1 for their own care
Outcomes
Table 2. Patient Outcomes (IR-4)
Type Outcome Specific measure or definition Source Timepoints
*Primary (effectiveness) Quality of Recovery Quality of Recovery 15 Instrument PRO Day 1
*Primary (safety) Intraoperative Awareness Modified Brice Interview Interview Day 1 or 30
Secondary (effectiveness) Delirium 3D-CAM Interview Day 1
Secondary (effectiveness) Quality of Recovery Quality of Recovery 15 Instrument PRO Day 0 & 2 & 7
Secondary (effectiveness) Functional status Change from preoperative baseline in
World Health Organization Disability
Assessment Scale 2.0
PRO Day 30 & 90
Secondary (safety) Intraoperative Undesired
Patient Movement
Moderate or Severe Undesired
Intraoperative Patient Movement
Clinician report Day 0
Secondary (safety) Stage 1 Acute kidney injury Creatinine increase of 50% or 0.3 mg/dl
from preoperative baseline (KDIG`O)
80
EHR Day 7
Secondary (safety) Respiratory failure Reintubation or continued mechanical
ventilation >6hr postoperatively
EHR Day 0
Secondary (safety) Mortality All-cause mortality NDI Query Day 30
Exploratory safety Intraoperative hypotension Duration of mean arterial pressure < 65
mmHg (minutes)
EHR During surgery
Exploratory safety Mortality All-cause mortality NDI Query Day 90
Exploratory effectiveness Daily step count Fitbit or Apple Watch MyDataHelps Day 7, 30
Exploratory effectiveness Daily stand hours Fitbit or Apple Watch MyDataHelps Day 7, 30
Exploratory effectiveness Sleep duration Fitbit or Apple Watch MyDataHelps Day 7, 30
Data flows and processes
Study Phases
• Feasibility Phase ( 18 months) Establish enrollment sites,
complete 200 patient feasibility RCT at Wash U & U-M, inform
full-study protocol
• Full Study Phase (5 years) @ at least 12 MPOG sites, to include
a 4 month ramp up period and full-scale enrollment of ~ 1
patient per weekday (22 / month)
THRIVE centers
Collaboration across functional centers
Projected Timeline
Dates Milestone
12/1/2021-6/1/2023
Feasibility Study Phase
6/1/2023-6/1/2028
Full Study Phase
10/1/2023 Begin patient enrollment (average across centers)
10/1/2027 Complete patient enrollment
6/1/2028 Full study phase end
6/1/2028-10/1/2028
Peer Review / Report Writing Period
Full scale phase
• Begin enrollment as early as 6/1/2023 (10/1/2023 likely)
• 12-18 MPOG centers
• 1042 patients/site, 22 per site/month, 1 per day
• Resource assumptions (per site)
– 10-15% faculty FTE
– Approximately 2 study coordinator FTE for enrollment
• Reimbursement
– Fixed cost for participant engagement activities
– Per patient reimbursement (~$1000 including PCORI 40% indirects)
What’s next
• Now
– Continued discussions with PCORI and contract signature for feasibility start
– Work with patient partners and MPOG sites to finalize pilot trial
– Get your feedback
• Soon
– Enroll 300 patients at Wash U & U Michigan for pilot
– Get your feedback
– Work with interested MPOG sites to re-assess interest, capacity, finances
• Later
– Contracting with MPOG sites
What have we learned
• The power of MPOG is
recognized by funders
• The group comes together
FAST for a good question
• Should be submitting more
grants to address
– Clinical questions
– Informatics
– Science of QI
– Participant perspectives
Thank You
