Recommendations of Enhanced Recovery Interventions for Patient's Clinical Team and Collection of Associated Data

The Periop Core Protocol is an administration structure designed to provide appropriate management of all aspects of the study, taking into account multiple factors including representation from clinics and hospitals that are participating in the trial, availability of skills and expertise related to trial conduct and statistical analysis, and content knowledge regarding acute illness, elective surgery, and the interventions that are being evaluated. Eligible patients will be randomized to a recommended set of standard of care treatments related to their surgery to identify those that improve outcomes as defined by hospital free days at 30 days from the date of the surgical encounter. The administration model is designed to provide effective operational and strategic management of the REMAP that operates in multiple UPMC facilities, is supported by multiple funding bodies and sponsors, and will evolve with addition of domains and interventions that are being evaluated.

The ERP domain under the Periop Core Protocol will evaluate the varying recommended combinations of perioperative treatments, in hopes to determine the optimal strategies for perioperative care based on surgery type and patient specific factors. In this study, patient care components within the preoperative, perioperative, and postoperative domains will be randomized with a machine learning REMAP technique. Optimal strategies combining the entire perioperative process will be analyzed that determine best outcomes for patients including hospital free days, reductions in postoperative nausea and vomiting, and improved pain control.

• Neuraxial Analgesia (Drug), also known as Intrathecal morphine/hydromorphone, IT morphine/hydromorphine: This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).
• Regional Block 1: Paravertebral (Drug), also known as Nerve Block: This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block)
• Perphenazine (Drug): This randomized group will receive 8 mg of perphenazine orally preoperatively.
• Aprepitant (Drug): This randomized group will receive 40 mg of aprepitant orally preoperatively.
• Dimenhydrinate (Drug): This randomized group will receive 25 mg of dimenhydrinate orally preoperatively.
• Ondansetron 4 MG (Drug): This randomized group will receive 4 mg of ondansetron orally.
• Dexamethasone (Drug): This randomized group will receive 4-5 mg of dexamethasone intravenously.
• Regional Block 2: QL1 (Drug), also known as Nerve Block: This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block)

Primary outcomes

• 30 Day Hospital Free Days [Day 0 - Day 30]: The primary endpoint for this domain is the REMAP Periop primary outcome of hospital free days at 30 days after the elective surgical encounter.

Secondary outcomes

• Change in Postoperative Nausea and Vomiting (PONV) by Measurement Incidences of Emesis Within 24 Hours Post Surgery [0 - 24 hours post-surgery]: Did the participant receive postoperative antiemetic medication within 24 hours of completion of surgery (number of participants who did receive postoperative antiemetics)
• Change in the Rate of Postoperative Opioid Use by Measurement of Oral Morphine Equivalents (OME) Measured 24 Hours After Surgery [0-24 hours post-surgery]: OME measurement is a method to compare and standardize different opioids administered to participants to account for varying strengths. OME is measured as a rate in milligrams per day and modeled as a continuous endpoint. For analysis purposes, OME was converted to log(OME) + 1

Sex: All, ages: 18 Years to any

Inclusion Criteria

1. Patient is seen in preoperative appointment prior to surgery
2. ≥ 18 years of age
3. Anticipated overnight hospital stay
4. Scheduled for elective abdominal surgery that utilizes ERP PowerPlans - placed into the patient's electronic chart at least one night before surgery
5. ERP Abdominal Complex Pathway PowerPlan (used for colorectal and gastrointestinal surgery)
6. ERP Bariatric Surgery Pathway PowerPlan
7. ERP Gynecology Oncology Pathway PowerPlan
8. ERP Whipple/Pancreas Pathway PowerPlan
9. ERP Open Liver Resection Pathway PowerPlan
10. Surgery is scheduled for one of the following UPMC sites:
11. UPMC Presbyterian Hospital
12. UPMC Passavant Hospital
13. UPMC Magee-Women's Hospital

Exclusion Critera

1. Death is deemed to be imminent or inevitable
2. Patient is pregnant < 18 years of age
3. Patients undergoing emergent/urgent surgery
4. Patients that are pregnant
5. Patients that have an eligible PowerPlan ordered less than one night before surgery

Participant flow

Outcome results

• 30 Day Hospital Free Days (Primary), Median, Number of hospital free days: PONV Optimal Prophylaxis 27 (25 to 28); PONV Supraoptimal Prophylaxis 27 (25 to 28); Neuraxial Analgesia 26 (24 to 28); Regional Analgesia Block 1 27 (25 to 28); Regional Analgesia Block 2 27 (25 to 28); Neuraxial and Regional Analgesia Block 1 27 (25 to 28); Neuraxial and Regional Analgesia Block 2 27 (25 to 28)
• Change in Postoperative Nausea and Vomiting (PONV) by Measurement Incidences of Emesis Within 24 Hours Post Surgery (Secondary), Count of participants, Participants: PONV Optimal Prophylaxis 271; PONV Supraoptimal Prophylaxis 246
• Change in the Rate of Postoperative Opioid Use by Measurement of Oral Morphine Equivalents (OME) Measured 24 Hours After Surgery (Secondary), Mean, mg/day: Neuraxial Analgesia 3.0 +/- 1.58; Regional Analgesia Block 1 3.7 +/- 1.23; Regional Analgesia Block 2 3.6 +/- 1.25; Neuraxial and Regional Analgesia Block 1 2.8 +/- 1.67; Neuraxial and Regional Analgesia Block 2 2.7 +/- 1.66

Adverse events

Time frame: from enrollment until 30 days after surgery

• Results publication: Holder-Murray J, Esper SA, Althans AR, Knight J, Subramaniam K, Derenzo J, Ball R, Beaman S, Luke C, La Colla L, Schott N, Williams B, Lorenzi E, Berry LR, Viele K, Berry S, Masters M, Meister KA, Wilkinson T, Garrard W, Marroquin OC, Mahajan A. REMAP Periop: a randomised, embedded, multifactorial adaptive platform trial protocol for perioperative medicine to determine the optimal enhanced recovery pathway components in complex abdominal surgery patients within a US healthcare system. BMJ Open. 2023 Dec 28;13(12):e078711. doi: 10.1136/bmjopen-2023-078711. PMID 38154902

• Study Protocol (PDF, 2023-06-09)
• Statistical Analysis Plan: Postoperative Nausea and Vomiting Domain SAP (PDF, 2024-03-07)
• Statistical Analysis Plan: PONV Adaptive Design Report (PDF, 2023-06-14)
• Statistical Analysis Plan: Analgesia Domain SAP (PDF, 2025-02-21)
• Statistical Analysis Plan: Analgesia Adaptive Design Report (PDF, 2023-06-14)
• Statistical Analysis Plan: Core Adaptive Design Report (PDF, 2013-06-14)

• Stephen Esper, MD, MBA, Study chair, University of Pittsburgh