REMAP Trial for Optimizing Surgical Outcomes at UPMC

NCT03861767 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: STUDY19090186
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aging

Keywords

Prehabilitation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Incidence of ICU Admission After Surgery

  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

  Day 90 from the date of the elective surgical procedure

• Venous Thromboembolic Events Including Deep Vein Thrombosis and Pulmonary Embolism

  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

Study Arms (10)

SPRY: Metformin LD-SC (low-dose, short course)

EXPERIMENTAL

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

SPRY: Metformin LD-IC (low-dose, intermediate course)

EXPERIMENTAL

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

SPRY: Metformin LD-LC (low-dose, long course)

EXPERIMENTAL

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

SPRY: Metformin ID-SC (intermediate-dose, short course)

EXPERIMENTAL

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

SPRY: Metformin ID-IC (intermediate-dose, intermediate course)

EXPERIMENTAL

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

SPRY: Metformin ID-LC (intermediate-dose, long course)

EXPERIMENTAL

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

SPRY: Metformin HD-SC (high-dose, short course)

EXPERIMENTAL

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

SPRY: Metformin HD-IC (high-dose, intermediate course)

EXPERIMENTAL

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

SPRY: Metformin HD-LC (high-dose, long course)

EXPERIMENTAL

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

SPRY: Placebo

PLACEBO COMPARATOR

Participants are randomized to receive dose matched placebo to take daily for either short-, intermediate-, or long-course.

Drug: Placebo

Interventions

Metformin ER DRUG

tablet

Also known as: Metformin Extended Release

SPRY: Metformin HD-IC (high-dose, intermediate course); SPRY: Metformin HD-LC (high-dose, long course); SPRY: Metformin HD-SC (high-dose, short course); SPRY: Metformin ID-IC (intermediate-dose, intermediate course); SPRY: Metformin ID-LC (intermediate-dose, long course); SPRY: Metformin ID-SC (intermediate-dose, short course); SPRY: Metformin LD-IC (low-dose, intermediate course); SPRY: Metformin LD-LC (low-dose, long course); SPRY: Metformin LD-SC (low-dose, short course)

Placebo DRUG

Matched placebo in doses of 1, 2 and 3 tablets to coincide with the 500, 1000, and 1500 mg arms.

SPRY: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Matthew Neal MD: lead
• University of Pittsburgh Medical Center: collaborator
• Berry Consultants: collaborator

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• 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.

  PMID: 32994242 DERIVED

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Recruitment was terminated early and was limited by the COVID-19 pandemic, as such the study is underpowered and could not meet its set goals. No patients fell in the high dose long course group since no participants were randomized to that group

Results Point of Contact

• Title: Matthew D. Neal, MD FACS
• Organization: UPMC

nealm2@upmc.edu

412-647-1158

Study Officials

• Matthew D Neal, MD, FACS

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: March 4, 2019
• Study Start: April 15, 2019
• Primary Completion: September 23, 2022
• Study Completion: September 23, 2022
• Last Updated: June 18, 2024
• Results First Posted: June 18, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Relevant data may be available 1 year following publication
• Access Criteria: Data access is subject to a methodologically sound proposal and the necessary data sharing agreements.

Locations

US (1)