REMAP Trial for Optimizing Surgical Outcomes at UPMC (UPMCREMAP)

Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Optimizing Surgical Outcomes at UPMC

The purpose of this project is to determine the effect of various interventions to improve patient outcome as defined by hospital free days at day 90 for adult patients undergoing elective surgery. Within this project, multiple studies may be conducted.

The structure of this project permits:

• the testing of multiple treatments at the same time within the same patient
• the use of early study results to provide better treatment options to future patients
• the removal of treatments which are shown to be less effective than the other treatments
• the addition of new treatments

The first study to be conducted under this project (IRB STUDY19090186) is the Strategies to Promote ResiliencY (SPRY) clinical trial (IRB PRO18060038).

The SPRY clinical trial will determine the effectiveness of Metformin on improving surgical outcomes among nondiabetic older adults who are scheduled for elective surgery.

Study Overview

• Status: Terminated
• Conditions: Aging
• Intervention / Treatment: Drug: Metformin ER; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC

Participation Criteria

Eligibility Criteria

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

Description

UPMC REMAP

Inclusion Criteria:

• Adult patient evaluated pre-operatively for elective surgery at UPMC
• Minimum lead time before surgery to provide domain specific intervention (range 7-180 days pre-operatively)
• Age greater to or equal to 18 years of age

Exclusion Criteria:

• Death is deemed to be imminent or inevitable
• Emergency surgical procedure without suitable lead-in time
• Previous participation in this REMAP within the last 90 days, flagged by elective or emergency surgical encounter at UPMC in the past 90 days

SPRY Domain

Inclusion Criteria:

• Age >= 60 years
• Age < 60 but evidence of comorbidity risk as represented by a Charlson Comorbidity Index of > 2 in 12 months prior to enrollment
• Able to take an oral medication in non-crushable pill form
• Women must be post-menopausal, which is defined as not having a menstrual period within the last 12 months

Exclusion Criteria:

• The treating clinician believes that participation in the domain would not be in the best interest of the patient
• Pre-existing diabetes type I or II
• Women of child-bearing potential
• Hospital stay <24 hours
• Presently taking metformin or prior use in the past 6 months

• Evidence of an absolute or relative contraindication to Metformin therapy

  • Known allergy to metformin
  • Acute or chronic metabolic acidosis with or without coma
  • Hemodialysis, end-stage renal disease, or Glomerular Filtration Rate (GFR) < 45 in the prior 30 days
  • Ongoing treatment with therapy known to have significant drug-drug interaction with metformin (carbonic anhydrase inhibitors, cimetidine, gliptins)
  • History of lactic acidosis
  • History of excessive alcohol intake
  • Severe hepatic dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPRY: Metformin LD-SC (low-dose, short course); LD-SC (low-dose, short course) Participants take Metformin ER 500 mg daily for 7-28 days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin LD-IC (low-dose, intermediate course); LD-IC (low-dose, intermediate course) Participants take Metformin ER 500 mg daily for 29-90 days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin LD-LC (low-dose, long course); LD-LC (low-dose, long course) Participants take Metformin ER 500 mg daily for 90+ days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin ID-SC (intermediate-dose, short course); ID-SC (intermediate-dose, short course) Participants take Metformin ER 1000 mg daily for 7-28 days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin ID-IC (intermediate-dose, intermediate course); ID-IC (intermediate-dose, intermediate course) Participants take Metformin ER 1000 mg daily for 29-90 days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin ID-LC (intermediate-dose, long course); ID-LC (intermediate-dose, long course) Participants take Metformin ER 1000 mg daily for 90+ days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin HD-SC (high-dose, short course); HD-SC (high-dose, short course) After a 7 day run-in of Metformin ER 1000 mg, participants take Metformin ER 1500 mg daily for 7-28 days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin HD-IC (high-dose, intermediate course); HD-IC (high-dose, intermediate course) After a 7 day run-in of Metformin ER 1000 mg, participants take Metformin ER 1500 mg daily for 29-90 days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Experimental: SPRY: Metformin HD-LC (high-dose, long course); HD-LC (high-dose, long course) After a 7 day run-in of Metformin ER 1000 mg, participants take Metformin ER 1500 mg daily for 90+ days prior to their elective surgical procedure as determined by the patient's scheduling of their surgery. Participants take this same dose of Metformin ER for 90 days after their surgical procedure.	Drug: Metformin ER; tablet; Other Names: Metformin Extended Release
Placebo Comparator: SPRY: Placebo; Participants are randomized to receive dose matched placebo to take daily for either short-, intermediate-, or long-course.	Drug: Placebo; Matched placebo in doses of 1, 2 and 3 tablets to coincide with the 500, 1000, and 1500 mg arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Free Days (HFD)	90 - the number of days during the index stay minus the number of days readmitted during the 90 days after surgery. Death within 90 days after surgery is recorded as -1 HFD.	Day 90 from the date of the elective surgical procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		Day 90 from the date of the elective surgical procedure
Incidence of ICU Admission After Surgery	The intended measure of this outcome is to get the rate of ICU admission per described group or the number of participants that had an ICU admission within each group.	Participants will be followed for the duration of their hospital admission, estimated to be 2-4 days in the event ICU admission is needed
Incidence and Total Number of Reoperation/Reintervention	This outcome is also intended to measure the rate of Reoperation/reintervention within each group or the total number of participants that had a Reoperation/reintervention within each group as shown below	Day 90 from the date of the elective surgical procedure
Venous Thromboembolic Events Including Deep Vein Thrombosis and Pulmonary Embolism	The intended measure from this outcome is to also show the rate of Venous thromboembolic events or the number of participants with Venous thromboembolic events within each group	Day 90 from the date of the elective surgical procedure
Number of Participants With Surgical Site Infection		Day 30 from the date of the elective surgical procedure
Number of Participants With Surgical Site Occurrence		Day 30 from the date of the elective surgical procedure
Organ Failure Free Days		Day 30 from the date of the elective surgical procedure
Hospital Length of Stay (LOS)		Participants will be followed for the duration of their hospital admission, estimated to be 2-4 days
ICU (Intensive Care Unit) Length of Stay (LOS)		Participants will be followed for the duration of their hospital admission, estimated to be 2-4 days, in the event admission to an ICU is needed
Hospital Readmission Rate		Day 90 from the date of the elective surgical procedure
Gastrointestinal Intolerance		From enrollment to day 90 after surgery
SAE (Serious Adverse Event) as Defined in Core Protocol (Mild, Moderate, Severe, Life Threatening/Disabling; Adjudicated as Related, Possibly Related, Unrelated)	The number of participants here includes the full cohort because adverse events were recorded for all participants while other outcome measures were only recorded for participants that underwent surgery	From enrollment to day 90 after surgery
Discharge Disposition		Participants will be followed for the duration of their hospital admission, estimated to be 2-4 days, in the event admission to an ICU is needed
In Hospital Mortality		Participants will be followed for the duration of their hospital admission, estimated to be 2-4 days, in the event admission to an ICU is needed.

Collaborators and Investigators

• Sponsor: Matthew Neal MD
• Collaborators: Berry Consultants; University of Pittsburgh Medical Center
• Investigators: Principal Investigator: Matthew D Neal, MD, FACS, University of Pittsburgh

Publications and helpful links

General Publications

• Reitz KM, Seymour CW, Vates J, Quintana M, Viele K, Detry M, Morowitz M, Morris A, Methe B, Kennedy J, Zuckerbraun B, Girard TD, Marroquin OC, Esper S, Holder-Murray J, Newman AB, Berry S, Angus DC, Neal M. Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients. BMJ Open. 2020 Sep 29;10(9):e037690. doi: 10.1136/bmjopen-2020-037690.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): September 23, 2022
• Study Completion (Actual): September 23, 2022

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Prehabilitation
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: STUDY19090186

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 methodologically 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