REMAP Trial for Optimizing Surgical Outcomes at UPMC

Phase 3

Terminated

Conditions: Aging

Interventions: Drug: Metformin ER
Drug: Placebo

Registration Number: NCT03861767

Lead Sponsor: Matthew Neal MD

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 302

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SPRY: Metformin ID-IC (intermediate-dose, intermediate course)	Metformin ER	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.
SPRY: Metformin HD-IC (high-dose, intermediate course)	Metformin ER	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.
SPRY: Metformin LD-SC (low-dose, short course)	Metformin ER	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.
SPRY: Metformin LD-IC (low-dose, intermediate course)	Metformin ER	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.
SPRY: Metformin ID-LC (intermediate-dose, long course)	Metformin ER	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.
SPRY: Metformin HD-SC (high-dose, short course)	Metformin ER	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.
SPRY: Metformin HD-LC (high-dose, long course)	Metformin ER	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.
SPRY: Metformin ID-SC (intermediate-dose, short course)	Metformin ER	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.
SPRY: Metformin LD-LC (low-dose, long course)	Metformin ER	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.
SPRY: Placebo	Placebo	Participants are randomized to receive dose matched placebo to take daily for either short-, intermediate-, or long-course.

Primary Outcome Measures

Name	Time	Method
Hospital Free Days (HFD)	Day 90 from the date of the elective surgical procedure	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Surgical Site Infection	Day 30 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	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
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	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.
Incidence and Total Number of Reoperation/Reintervention	Day 90 from the date of the elective surgical procedure	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
Number of Participants With Surgical Site Occurrence	Day 30 from the date of the elective surgical procedure
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
Organ Failure Free Days	Day 30 from the date of the elective surgical procedure
Mortality	Day 90 from the date of the elective surgical procedure
Hospital Readmission Rate	Day 90 from the date of the elective surgical procedure
Gastrointestinal Intolerance	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.
Hospital Length of Stay (LOS)	Participants will be followed for the duration of their hospital admission, estimated to be 2-4 days
SAE (Serious Adverse Event) as Defined in Core Protocol (Mild, Moderate, Severe, Life Threatening/Disabling; Adjudicated as Related, Possibly Related, Unrelated)	From enrollment to day 90 after surgery	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