History of Changes for Study: NCT04510194

MET-Covid Trial - METformin for Prevention and Outpatient Treatment of COVID-19

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Study Record Versions

Version	Submitted Date	Changes
1	August 10, 2020	None (earliest Version on record)
2	August 24, 2020	Eligibility and Study Status
3	October 30, 2020	Outcome Measures, Study Status, Eligibility, Arms and Interventions, Study Design and Study Description
4	November 23, 2020	Outcome Measures, Arms and Interventions, Study Description, Study Status, Study Identification, References, Eligibility and Study Design
5	January 12, 2021	Recruitment Status, Study Status, Study Identification, Contacts/Locations and Oversight
6	January 15, 2021	Contacts/Locations and Study Status
7	February 17, 2021	Outcome Measures, Study Status, Arms and Interventions, Study Design, Study Description, Study Identification, Contacts/Locations, Eligibility and Sponsor/Collaborators
8	May 3, 2021	Arms and Interventions, Study Description, Study Status, Eligibility and Study Design
9	May 17, 2021	Contacts/Locations, Study Status, Eligibility, Study Identification, Outcome Measures and Arms and Interventions
10	May 21, 2021	References and Study Status
11	June 1, 2021	Study Status and Arms and Interventions
12	July 30, 2021	Contacts/Locations and Study Status
13	September 13, 2021	Study Status and Study Identification
14	September 30, 2021	Outcome Measures, Study Design, Study Identification, Study Description and Study Status
15	November 16, 2021	Study Status
16	January 20, 2022	Outcome Measures, Study Status, Study Design, Document Section, Eligibility, Arms and Interventions and Study Description
17	March 2, 2022	Recruitment Status, Study Status, Contacts/Locations and Outcome Measures
18	August 5, 2022	Study Status
19	April 18, 2023	Quality Control Review has not concluded Returned: May 11, 2023 Document Section, Study Status, Outcome Measures, Study Design
20	May 24, 2023	Quality Control Review has not concluded Returned: June 15, 2023 Adverse Events, Baseline Characteristics, Study Status, Outcome Measures, Participant Flow and Study Design
21	June 21, 2023	Study Status, Adverse Events and Outcome Measures
22	April 22, 2024	Recruitment Status and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	Metformin
Brief Title:	MET-Covid Trial - METformin for Prevention and Outpatient Treatment of COVID-19
Official Title:	MET-Covid Trial - METformin for Prevention and Outpatient Treatment of COVID-19
Secondary IDs:

Study Status


Record Verification:	October 2020
Overall Status:	Not yet recruiting
Study Start:	November 2020
Primary Completion:	September 2021 [Anticipated]
Study Completion:	September 2021 [Anticipated]

First Submitted:	August 7, 2020
First Submitted that Met QC Criteria:	August 10, 2020
First Posted:	August 12, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	October 30, 2020
Last Update Posted:	November 3, 2020 [Actual]

Sponsor/Collaborators


Sponsor:	University of Minnesota
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

The purpose of this trial is to:

Determine whether metformin can reduce the severity of COVID-19 disease;
Determine whether metformin can prevent symptomatic COVID-19 disease;
Determine whether metformin can prevent SARS-CoV-2 infection (seroconversion of SARS-CoV2 antibody tests or PCR positivity)

Detailed Description:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly spreading viral infection causing COVID-19 disease. There currently is no preventive or outpatient treatment therapy for Covid-19. While vaccine development for SARS-CoV-2 has been promising, there may be reduced willingness among the public to receive a vaccine developed so quickly. Briefly, this trial has been designed as a parallel-enrolling trial in which there is a prevention cohort and treatment cohort. The sequential randomization between the two will help understand the duration of metformin necessary for benefit, as all the observational data is in persons who were on metformin before they were hospitalized. The fully powered trial will enroll 3,304 patients. But first, a stage 1 trial of the treatment-cohort will be launched. This first trial is a substudy with laboratory outcomes (70 patients will be enrolled). The intervention is metformin, a biguanide, administered in its immediate release formation, 1,500mg daily.

Conditions


Conditions:	Covid19 SARS-CoV Infection
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 2/Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	4
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	70 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Prevention Arm - Treatment Group Participants in the prevention arm of the trial are those who do not test positive for SARS-COV-2 infection at the time of screening. Participants in this arm and group will receive the study drug.	Drug: Metformin Metformin; immediate release formation; 1,500mg daily Other Names: glucophage
Placebo Comparator: Prevention Arm - Placebo Group Participants in the prevention arm of the trial are those who do not test positive for SARS-COV-2 infection at the time of screening. Participants in this arm and group will receive the placebo.	Drug: Placebo placebo; size-matched to study drug
Experimental: Treatment Arm - Treatment Group Participants in the treatment arm of the trial are those who test positive for SARS-COV-2 infection at the time of screening. Participants in this arm and group will receive the study drug.	Drug: Metformin Metformin; immediate release formation; 1,500mg daily Other Names: glucophage
Placebo Comparator: Treatment Arm - Placebo Group Participants in the treatment arm of the trial are those who test positive for SARS-COV-2 infection at the time of screening. Participants in this arm and group will receive the placebo.	Drug: Placebo placebo; size-matched to study drug

Outcome Measures


Primary Outcome Measures:
1.	Change in C-Reactive Protein [ Time Frame: 10 days ] This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum concentrations of c-reactive protein (mg/L) from baseline to 5 days and baseline to 10 days.
2.	Change in Albumin [ Time Frame: 10 days ] This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum concentrations of albumin (g/dL) from baseline to 5 days and baseline to 10 days.
3.	Change in Viral load [ Time Frame: 10 days ] This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum viral load (copies per ml of blood) from baseline to 5 days and baseline to 10 days.
4.	Rate of Death due to COVID-19 [ Time Frame: 28 days ] Outcome reported as the percent of participants in each arm who expire due to COVID-19 within 28 days of the initiation of treatment.
5.	Rate of Hospitalization due to COVID-19 [ Time Frame: 14 days ] Outcome reported as the percent of participants in each arm who are admitted to hospital due to COVID-19 within 14 days of the initiation of treatment.
6.	Rate of Emergency Department Utilization [ Time Frame: 14 days ] Outcome reported as the percent of participants in each arm who utilize emergency department services due to COVID-19 within 14 days of the initiation of treatment.
7.	Incidence of all-cause study medicine discontinuation [ Time Frame: 28 days ] This is the primary outcome for the Prevention Cohort. Outcome reported as the percent of participants in each arm who discontinue use of the study drug due to any reason.
Secondary Outcome Measures:
1.	Incidence of Possible COVID-19 Symptoms [ Time Frame: 14 days, 28 days ] Outcome measured using a visual analog Scale of COVID-19 symptom maximum severity at days 14 and 28 among those who develop PCR or antibody positivity. Scale ranges from 1-10 with higher scores indicating great symptom severity.
2.	Disease Severity Rating [ Time Frame: 7, 14, and 28 days ] Outcome reported as the percent of participants who fall into each of 8 ordinal categories on days 7, 14, and 28 of study treatment. Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.
3.	Global Health Survey (PROMIS survey) [ Time Frame: 60 days ] The PROMIS Gobal-10 is a 10-item short-form survey measuring symptoms, functioning, and healthcare-related quality of life for a wide variety of chronic diseases and conditions. Nine items are rated on a 5-point scale. Item 7 is rated on an 11-point scale and then transformed to a 5-point scale. Items 3, 6, 7, and 8 are scored in reverse. Item scores are summed to calculate a total raw score. Raw scores are then matched with a t-score using a scoring table. Outcome will be reported as t-score. T-scores range from 16.2 to 67.7 with higher scores indicating greater global health.
4.	Seroconversion of SARS-Cov2 Antibodies OR SARS-Cov2 PCR Positivity (Prevention Cohort Only) [ Time Frame: up to 3 months ] Outcome reported as the percent of participants in the treatment and placebo groups who contract SARS-CoV-2 during participation in the prevention arm of the study.

Eligibility


Minimum Age:	30 Years
Maximum Age:	85 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	Inclusion Criteria: Prevention Arm: Negative IgM, IgG antibody for SARS-CoV-2 Glomerular Filtration Rate (GFR) > 45ml/min/1.73 m2 Patient has medical record visible within the Electronic Health Record (EHR) program of participating sites Body Mass Index (BMI) >= 25kg/m2 by self-report height/weight or >= 23kg/m2 in patients who self-identify as South Asian or Latinx Treatment Arm: Positive laboratory test for active SARS-CoV-2 viral infection based on local laboratory standard (+PCR) Glomerular Filtration Rate (GFR) > 45ml/min/1.73 m2 Patient has medical record visible within the Electronic Health Record (EHR) program of participating sites Body Mass Index (BMI) >= 25kg/m2 by self-report height/weight or >= 23kg/m2 in patients who self-identify as South Asian or Latinx Exclusion Criteria: Currently taking metformin or prior adverse reaction to metformin Electronic medical record history of kidney disease, defined as: Any history of dialysis Estimated Glomerular Filtration Rate (eGFR) of < 45ml/min/1.73 m2 (must be have been measured within 6 months of enrollment) Other kidney disease that in the opinion of the investigator would affect clearance Electronic medical record history of severe liver disease Other liver disease that in the opinion of the investigator, would affect metformin clearance Documented AST or ALT > 3 times the upper limit of normal within 3 months of randomization (if available in electronic medical record) Electronic Health Record history of New York Heart Association (NYHA) Stage 3 or 4 heart failure Enrollment in another blinded randomized drug clinical trial for COVID History of Lactic Acidosis Patients taking the following medications: insulin, sulfonylurea, hydroxychloroquine, dolutegravir, patiromer, ranolazine, tafenoquine Alcohol use disorder

Contacts/Locations


Central Contact Person:	Carolyn Bramante, MD Telephone: 612-624-5624 Email: Covid19trial@umn.edu
Study Officials:	Carolyn Bramante, MD Principal Investigator University of Minnesota
Locations:

IPDSharing


Plan to Share IPD:	Undecided

References


Links:
Available IPD/Information: