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

Randomized, Embedded, Multifactorial Adaptive Platform for Perioperative Medicine at UPMC (UPMC REMAP): Core Protocol - Enhanced Recovery Protocols (ERP)

This REMAP Periop ERP domain study falls under the Periop Core Protocol, which compares the different recommended strategies for enhancing recovery through the use of various standard of care treatments before, during and after surgery in all patients with elective surgical encounters at UPMC who meet eligibility criteria.

The ERP domain seeks to enhance recovery by optimizing strategies of perioperative care through evaluating combinations of perioperative treatment, which consists of preoperative, intraoperative and postoperative care. Optimal combinations of perioperative care will be generated and analyzed to determine the best outcomes for patients as defined by reduction in hospital free days, reduction in postoperative nausea and vomiting, and improved pain control.

Study Overview

• Status: Completed
• Conditions: Perioperative Optimization
• Intervention / Treatment: Drug: Neuraxial Analgesia; Drug: Regional Block 1: Paravertebral; Drug: Perphenazine; Drug: Ondansetron 4 MG; Drug: Dexamethasone; Drug: Aprepitant; Drug: Dimenhydrinate; Drug: Regional Block 2: QL1

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3395
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Passavant
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Magee-Womens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PONV Optimal Prophylaxis & Neuraxial Analgesia; PONV Pre-op -perphenazine Induction -dexamethasone Emergence -ondansetron Analgesia Intrathecal Morphine	Drug: Neuraxial Analgesia; This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).; Other Names: Intrathecal morphine/hydromorphone; IT morphine/hydromorphine; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.
Active Comparator: PONV Supraoptimal Prophylaxis & Neuraxial Analgesia; PONV Pre-op; aprepitant; dimenhydrinate; perphenazine; ondansetron Induction -dexamethasone Emergence -ondansetron Analgesia Intrathecal morphine	Drug: Neuraxial Analgesia; This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).; Other Names: Intrathecal morphine/hydromorphone; IT morphine/hydromorphine; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Aprepitant; This randomized group will receive 40 mg of aprepitant orally preoperatively.; Drug: Dimenhydrinate; This randomized group will receive 25 mg of dimenhydrinate orally preoperatively.
Active Comparator: PONV Supraoptimal Prophylaxis & Regional Analgesia Block 1; PONV Pre-op; aprepitant; dimenhydrinate; perphenazine; ondansetron Induction -dexamethasone Emergence -ondansetron Analgesia Paravertebral block	Drug: Regional Block 1: Paravertebral; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Aprepitant; This randomized group will receive 40 mg of aprepitant orally preoperatively.; Drug: Dimenhydrinate; This randomized group will receive 25 mg of dimenhydrinate orally preoperatively.
Active Comparator: PONV Supraoptimal Prophylaxis & Regional Analgesia Block 2; PONV Pre-op; aprepitant; dimenhydrinate; perphenazine; ondansetron Induction -dexamethasone Emergence -ondansetron Analgesia QL1	Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Aprepitant; This randomized group will receive 40 mg of aprepitant orally preoperatively.; Drug: Dimenhydrinate; This randomized group will receive 25 mg of dimenhydrinate orally preoperatively.; Drug: Regional Block 2: QL1; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block
Active Comparator: PONV Supraoptimal Prophylaxis & Neuraxial and Regional Analgesia Block 1; PONV Pre-op; aprepitant; dimenhydrinate; perphenazine; ondansetron Induction -dexamethasone Emergence -ondansetron Analgesia IT morphine and Paravertebral	Drug: Neuraxial Analgesia; This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).; Other Names: Intrathecal morphine/hydromorphone; IT morphine/hydromorphine; Drug: Regional Block 1: Paravertebral; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Aprepitant; This randomized group will receive 40 mg of aprepitant orally preoperatively.; Drug: Dimenhydrinate; This randomized group will receive 25 mg of dimenhydrinate orally preoperatively.
Active Comparator: PONV Supraoptimal Prophylaxis & Neuraxial and Regional Analgesia Block 2; PONV Pre-op; aprepitant; dimenhydrinate; perphenazine; ondansetron Induction -dexamethasone Emergence -ondansetron Analgesia IT morphine and QL1	Drug: Neuraxial Analgesia; This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).; Other Names: Intrathecal morphine/hydromorphone; IT morphine/hydromorphine; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Aprepitant; This randomized group will receive 40 mg of aprepitant orally preoperatively.; Drug: Dimenhydrinate; This randomized group will receive 25 mg of dimenhydrinate orally preoperatively.; Drug: Regional Block 2: QL1; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block
Active Comparator: PONV Optimal Prophylaxis & Regional Analgesia Block 1; PONV Pre-op -perphenazine Induction -dexamethasone Emergence -ondansetron Analgesia Paravertebral Block	Drug: Regional Block 1: Paravertebral; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.
Active Comparator: PONV Optimal Prophylaxis & Regional Analgesia Block 2; PONV Pre-op -perphenazine Induction -dexamethasone Emergence -ondansetron Analgesia QL1	Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Regional Block 2: QL1; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block
Active Comparator: PONV Optimal Prophylaxis and Neuraxial & Regional Analgesia Block 1; PONV Pre-op -perphenazine Induction -dexamethasone Emergence -ondansetron Analgesia Intrathecal Morphine & Paravertebral Block	Drug: Neuraxial Analgesia; This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).; Other Names: Intrathecal morphine/hydromorphone; IT morphine/hydromorphine; Drug: Regional Block 1: Paravertebral; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.
Active Comparator: PONV Optimal Prophylaxis and Neuraxial & Regional Analgesia Block 2; PONV Pre-op -perphenazine Induction -dexamethasone Emergence -ondansetron Analgesia Intrathecal Morphine & QL1	Drug: Neuraxial Analgesia; This randomized group will receive a neuraxial morphine injection (intrathecal morphine/hydromorphone).; Other Names: Intrathecal morphine/hydromorphone; IT morphine/hydromorphine; Drug: Perphenazine; This randomized group will receive 8 mg of perphenazine orally preoperatively.; Drug: Ondansetron 4 MG; This randomized group will receive 4 mg of ondansetron orally.; Drug: Dexamethasone; This randomized group will receive 4-5 mg of dexamethasone intravenously.; Drug: Regional Block 2: QL1; This randomized group will receive regional technique analgesia with sodium channel nerve blockade pharmacotherapy (ie nerve block); Other Names: Nerve Block

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 Day Hospital Free Days	The primary endpoint for this domain is the REMAP Periop primary outcome of hospital free days at 30 days after the elective surgical encounter.	Day 0 - Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Postoperative Nausea and Vomiting (PONV) by Measurement Incidences of Emesis Within 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)	0 - 24 hours post-surgery
Change in the Rate of Postoperative Opioid Use by Measurement of Oral Morphine Equivalents (OME) Measured 24 Hours After 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	0-24 hours post-surgery

Collaborators and Investigators

• Sponsor: Jennifer Holder-Murray
• Collaborators: Berry Consultants
• Investigators: Study Chair: Stephen Esper, MD, MBA, University of Pittsburgh

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): March 21, 2025
• Study Completion (Actual): March 21, 2025

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: length of stay; perioperative; postoperative nausea and vomiting; readmission; enhanced recovery; ERP; patient-directed care; randomized embedded multifactorial adaptive platform; REMAP; 90-day hospital free days; perioperative optimization; oral morphine equivalents
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Signs and Symptoms, Digestive; Vomiting; Nausea; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Postoperative Nausea and Vomiting; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Surgical Procedures, Operative; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Imidazoles; Amines; Indoles; Purinones; Purines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Anesthesia and Analgesia; Pregnadienetriols; Heterocyclic Compounds, 4 or More Rings; Ethylamines; Neurosurgical Procedures; Morpholines; Oxazines; Drug Combinations; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Heterocyclic Compounds, 3-Ring; Anesthesia, Conduction; Anesthesia; Phenothiazines; Carbazoles; Benzhydryl Compounds; Xanthines; Denervation; Theophylline; Diphenhydramine; Aprepitant; Dexamethasone; Ondansetron; Hydromorphone; Dimenhydrinate; Perphenazine; Nerve Block
• Other Study ID Numbers: STUDY19030022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant-level data underlying the results reported in journal articles, subject to appropriate security controls, may be available for sharing with other researchers.
• IPD Sharing Time Frame: Relevant data may be available 1 year following publication.
• IPD Sharing Access Criteria: Data access is subject to a methodically sound proposal and the necessary data sharing agreements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No