Metformin Use in Patients Undergoing Total Joint Replacement Surgery

Perioperative Metformin Use in Patients Undergoing Total Joint Replacement Surgery: A Pilot Study

The goal of this pilot, randomized, single-blind, placebo-controlled trial is to evaluate the feasibility of and provide preliminary information for a multi-center randomized controlled trial that will assess the effects of metformin on blood sugar control in patients after total hip or total knee replacement surgery.

The primary objective of this study is to assess the feasibility of conducting a large, randomized trial with regards to timely recruitment, study drug administration, protocol adherence, and overall retention in patients undergoing total joint arthroplasty.

Secondarily, the investigators aim to obtain preliminary estimates of group-specific outcome means and variances for primary and secondary outcomes of a larger future trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperglycemia
• Intervention / Treatment: Other: Placebo; Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Aidan Morrell; Phone Number: 5034948211; Email: morrella@ohsu.edu
• Study Contact Backup: Name: Ryland Kagan; Phone Number: 5034945649; Email: kagan@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
      • Contact: Ryland Kagan; Phone Number: 503-494-5649; Email: kagan@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, age 18-99 years
• Undergoing total hip or total knee arthroplasty, including elective, primary, and revision surgeries
• Ability to take oral medication and be willing to adhere to the prescribed metformin regimen regardless of current, past, or no metformin use.

Note: Patients with or without type 2 diabetes are considered eligible. (E.g.)

• Type 2 diabetic on metformin
• Type 2 diabetic on metformin and other medication, including insulin
• Type 2 diabetic on medication but not metformin
• Pre-diabetic
• Non-diabetic

Exclusion Criteria:

• Advanced renal insufficiency (glomerular filtration rate (GFR) < 45, or chronic kidney disease (CKD) stage 3B or higher)
• Advanced liver cirrhosis or failure (Child-Pugh class B or C)
• Congestive heart failure (New York Heart Association (NYHA) class 3 or 4)
• Current alcohol abuse within 30 days of surgery (>4 standard servings daily for men, >3 standard servings daily for women)
• Type 1 diabetes
• Received contrast dye within 48 hours of surgery
• Vulnerable populations: Children, pregnant women, neonates, decisionally impaired adults, prisoners

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo tablet	Other: Placebo; Placebo tablet
Experimental: Treatment; Oral metformin hydrochloride	Drug: Metformin; Metformin 500mg oral once daily for 7 days, increased to 1000mg (500mg twice daily) for another 7 days, taken in morning and evening with meals, for a total of 14 days of treatment prior to surgery. Continue dose on day of surgery and up to post operative day 2, or until time of discharge, whichever happens first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of participant enrollment	Feasibility defined by an average of four participants per month successfully enrolled and randomized.	3 months
Rate of appropriate study drug administration	Feasibility defined by ≥90% participants receiving 1000mg metformin or placebo daily by day of surgery, assessed via combination of self-report and counting of remaining tablets.	3 months
Rate of participant adherence to trial intervention per protocol	Feasibility defined by ≥90% participant adherence to trial intervention per protocol.	3 months
Rate of participant retention to 90-day follow up	Feasibility defined by ≥90% retention to follow up at 90 days.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative glycemic variability	Defined as coefficient of variation (CV) = standard deviation / mean of blood glucose levels	3 months
Sliding scale insulin utilization	Measured by total number of units administered from time of surgery to discharge.	3 months
Hospital length of stay	Measured in days.	3 months
90-day Rate of surgical site infection	Defined by criteria published by Centers for Disease Control and Prevention.	3 months
90-day Rate of periprosthetic joint infection	Defined by criteria published in 2018 by Musculoskeletal Infection Society (MSIS).	3 months
90-day Rate of mortality		3 months
90-day rate of readmission		3 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Ryland Kagan, Oregon Health and Science University

Publications and helpful links

Helpful Links

• Metformin labeling

Study record dates

Study Major Dates

• Study Start (Estimated): February 26, 2024
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Arthroplasty; Metformin; Knee; Hip; glycemic variability
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: STUDY00025798

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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