REMAP Trial for Optimizing Surgical Outcomes at UPMC (UPMCREMAP)

Matthew Neal MD

Status and phase: Terminated; Phase 3

Conditions: Aging

Treatments: Drug: Placebo; Drug: Metformin ER

Study type: Interventional

Funder types: Other

Identifiers

NCT03861767

STUDY19090186

Details and patient eligibility

About

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.

Enrollment: 302 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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302 participants in 10 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

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

Experimental group

Description:

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.

Treatment:

Drug: Metformin ER

SPRY: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo