REMAP Trial for Optimizing Surgical Outcomes at UPMC

Study Overview
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Brief Summary
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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.

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

Conditions
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Aging

Intervention / Treatment
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* Drug: Metformin ER
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPRY: Metformin LD-SC (low-dose, short course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin LD-IC (low-dose, intermediate course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin LD-LC (low-dose, long course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin ID-SC (intermediate-dose, short course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin ID-IC (intermediate-dose, intermediate course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin ID-LC (intermediate-dose, long course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin HD-SC (high-dose, short course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin HD-IC (high-dose, intermediate course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Experimental: SPRY: Metformin HD-LC (high-dose, long course)<br>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<br>* tablet<br>* Other names: Metformin Extended Release;|
| Placebo Comparator: SPRY: Placebo<br>Participants are randomized to receive dose matched placebo to take daily for either short-, intermediate-, or long-course. | Drug: Placebo<br>* Matched placebo in doses of 1, 2 and 3 tablets to coincide with the 500, 1000, and 1500 mg arms.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prehabilitation