ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)

Covid19 Clinical Trial

Official title:

ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06042855
• Other study ID #: Pro00107921_G
• Secondary ID: 3U24TR001608-05W
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 5, 2023
• Est. completion date: November 2024

Study information

• Verified date: June 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness of repurposed medications (study drug(s) in reducing symptoms of non-hospitalized participants with mild to moderate COVID-19. Participants will receive either study drug or placebo. Participants will self-report any new or worsening symptoms or medical events experienced while taking study drug or placebo. This study is intended to be all remote with no in person visits, unless the study team feels it is in the best interest of a participant to be seen in person.

Prior and current drug arms are listed on clinicaltrials.gov and will be updated with the activation of any new drug arms. Each study arm will also have its own clinicaltrials.gov entry and will include "Pro00107921" in the Unique Protocol ID.

Description:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that first emerged in December 2019 and has since caused a global pandemic unseen in almost a century with respect to the number of cases and overall mortality. The clinical disease related to SARS-CoV-2 is referred to as Coronavirus Disease 2019 (COVID-19). Over 2020, advances were made for treatment of COVID-19 and several vaccinations have received emergency use authorization for prevention of SARS-CoV-2 infections. However, the pandemic continues to evolve with new variants and surges of infections in different regions of the world, requiring an ongoing evidence-generating platform, in particular for the treatment of COVID-19 infection in the outpatient setting.

This proposed platform protocol can serve as an evidence generating system for prioritized drugs repurposed from other indications with an established safety record and preliminary evidence of clinical efficacy for the treatment of COVID-19. The ultimate goal is to evaluate if repurposed medications can make participants feel better faster and reduce death and hospitalization.

This platform protocol is designed to be flexible so that it is suitable for a wide range of settings within healthcare systems and in community settings where it can be integrated into routine COVID-19 testing programs and subsequent treatment plans. This platform protocol will enroll participants in an outpatient setting with a confirmed polymerase chain reaction (PCR) or antigen test for SARS-CoV-2.

Participants will be randomized to study drugs or placebo based on the arms that are actively enrolling at the time of randomization. Study drugs may be added or removed according to adaptive design and/or emerging evidence. When there are multiple study drugs available, randomization will occur based on appropriateness of each drug for the participant as determined by the study protocol and investigator and participant equipoise. Each participant will be required to randomize to at least one study drug versus placebo. The probability of placebo to treatment will remain the same regardless of eligibility decisions.

Eligible participants will be randomized (1:1), in a blinded fashion, to either the study drug arm or placebo arm in addition to standard of care. As additional study drugs are added, the randomization will be altered to leverage placebo data across arms. Participants will receive a complete supply study drug or placebo with the quantity depending on the study drug/placebo to which they are randomized.

All study visits are designed to be remote. However, screening and enrollment may occur in-person at sites and unplanned study visits may occur in-person or remotely, as deemed appropriate by the site investigator for safety purposes. Participants will be asked to complete questionnaires and report safety events during the study. Participants will be prompted by the online system to report safety events and these will be reviewed and confirmed via medical records and site staff, as necessary.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15000
• Est. completion date: November 2024
• Est. primary completion date: June 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Eligibility for overall study are listed below. There may be additional appendix-specific criteria.

Inclusion Criteria:

• Completed Informed Consent

• Age = 30 years old

• Confirmed SARS-CoV-2 infection by any authorized or approved polymerase chain reaction (PCR) or antigen test collected within 10 days of screening

• Two or more current symptoms of acute infection for =7 days. Symptoms include the following: fatigue, dyspnea, fever, cough, nausea, vomiting, diarrhea, body aches, chills, headache, sore throat, nasal symptoms, new loss of sense of taste or smell

Exclusion Criteria:

• Current or recent (within 10 days of screening) hospitalization for COVID-19 infection

• Current or planned participation in another interventional trial to treat COVID-19, at the discretion of the study principal investigator (PI)

• Current or recent use (within the last 14 days) of study drug or study drug/device combination

• Known allergy/sensitivity or any hypersensitivity to components of the study drug or placebo

• Known contraindication(s) to study drug including prohibited concomitant medications

• Previous or current enrollment in the ACTIV-6 trial

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Other:
• Placebo
Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug.

Drug:
• Metformin
Metformin IR tablets contain the active metformin hydrochloride and inactive ingredients including povidone and magnesium stearate. Commercially available metformin 500 mg tablets will be provided.

Locations

Country	Name	City	State
United States	Christus Saint Frances Hospita	Alexandria	Louisiana
United States	Express Family Clinic	Allen	Texas
United States	Emory Healthcare	Atlanta	Georgia
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Focus Clinical Research Solutions	Bayonne	New Jersey
United States	Boston Medical Center	Boston	Massachusetts
United States	Diabetes and Endocrinology Assoc. of Stark County	Canton	Ohio
United States	A New Start II, LLC	Central City	Kentucky
United States	Chandler Regional Medical Center	Chandler	Arizona
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern Univesity	Chicago	Illinois
United States	Olivo Wellness Medical Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Vaidya MD PLLC	Clayton	North Carolina
United States	Geriatrics and Medical Associates	Clinton	New York
United States	Essential Medical Care, Inc.	College Park	Georgia
United States	Doctors Medical Group of Colorado Springs, P.C.	Colorado Springs	Colorado
United States	Pine Ridge Family Medicine Inc.	Colorado Springs	Colorado
United States	University of Missouri - Columbia	Columbia	Missouri
United States	Clincept, LLC	Columbus	Georgia
United States	HOPE Clinical Research and Wellness	Conyers	Georgia
United States	David Kavtaradze MD, Inc.	Cordele	Georgia
United States	Ananda Medical Clinic	Dearborn	Michigan
United States	Arena Medical Group	Deerfield Beach	Florida
United States	GFC of Southeastern Michigan, PC	Detroit	Michigan
United States	Romancare Health Services	Detroit	Michigan
United States	Elite Family Practice	Douglasville	Georgia
United States	Essentia Health	Duluth	Minnesota
United States	Maria Medical Center, PLLC	Dunn	North Carolina
United States	The Heart and Medical Center	Durant	Oklahoma
United States	Duke Clinical Research Institute	Durham	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	DHR Health Institute for Research	Edinburg	Texas
United States	Texas Tech University Health Sciences Center	El Paso	Texas
United States	NorthShore Medical Group	Evanston	Illinois
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Texas Health Physicians Group	Fort Worth	Texas
United States	Clinical Trials Center of Middle TN	Franklin	Tennessee
United States	Lupus Foundation of Gainesville	Gainesville	Florida
United States	University of Florida Health	Gainesville	Florida
United States	Lamb Health, LLC	Gilbert	Arizona
United States	Comprehensive Pain Management and Endocrinology	Henderson	Nevada
United States	Rapha Family Wellness	Hendersonville	Tennessee
United States	L and A Morales Healthcare, Inc	Hialeah	Florida
United States	Highlands Medical Associates, P.A.	Highlands	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Hugo Medical clinic	Hugo	Oklahoma
United States	Family Practice Doctors P.A.	Humble	Texas
United States	Texas Health Physicians Group	Irving	Texas
United States	AMRON Vitality and Wellness Center, LLC	Jacksonville	Florida
United States	University of Florida-JAX-ASCENT	Jacksonville	Florida
United States	Kintex Group Texas LLC, DBA Activian Clinical Research	Kingwood	Texas
United States	Medical Specialists of Knoxville	Knoxville	Tennessee
United States	Sunshine Walk In Clinic	Lake Mary	Florida
United States	Advanced Medical Care, Ltd	Lake Zurich	Illinois
United States	Lakeland Regional Medical Center	Lakeland	Florida
United States	Health Quality Primary Care	Lawrence	Massachusetts
United States	University of Arkansas Medical Sciences	Little Rock	Arkansas
United States	Christ the King Health Care, P.C.	Loganville	Georgia
United States	Miller Family Practice, LLC	Macon	Georgia
United States	Raritan Bay Primary Care & Cardiology Associates	Matawan	New Jersey
United States	Loyola University Medical Center	Maywood	Illinois
United States	First Care Medical Clinic	Mesa	Arizona
United States	Jackson Memorial Hospital	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Well Pharma Medical Research	Miami	Florida
United States	The Angel Medical Research Corporation	Miami Lakes	Florida
United States	Franciscan Health Michigan City	Michigan City	Indiana
United States	University of Minnesota	Minneapolis	Minnesota
United States	Del Pilar Medical and Urgent Care	Mishawaka	Indiana
United States	TriHealth, Inc	Montgomery	Ohio
United States	Lapis Clinical Research	Mooresville	North Carolina
United States	Bucks County Clinical Research	Morrisville	Pennsylvania
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	University Medical Center- New Orleans	New Orleans	Louisiana
United States	Weill Cornell Medical College	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Assuta Family Medical Group APMC	North Hollywood	California
United States	Innovation Clinical Trials Inc.	Palmetto Bay	Florida
United States	Stanford	Palo Alto	California
United States	University Diagnostics and Treatment Clinic	Pasadena	Texas
United States	G&S Medical Associates, LLC	Paterson	New Jersey
United States	Trident Health Center	Peoria	Arizona
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Lice Source Services Plantation	Plantation	Florida
United States	Jadestone Clinical Research, LLC	Rockville	Maryland
United States	Premier Health	Saint Petersburg	Florida
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Christus St. Vincent Regional Medical Center	Santa Fe	New Mexico
United States	Superior Clinical Research	Smithfield	North Carolina
United States	Providence Medical Research Center	Spokane	Washington
United States	Tabitha B. Fortt, M.D., LLC	Stamford	Connecticut
United States	Jeremy W. Szeto, D.O., P.A.	Sugar Land	Texas
United States	Olive View - UCLA Medical Center	Sylmar	California
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	UF Health Precision Health Research	The Villages	Florida
United States	Ascension St. John	Tulsa	Oklahoma
United States	Mediversity Healthcare	Turnersville	New Jersey
United States	George Washington University Hospital	Washington	District of Columbia
United States	University of Texas Rio Grande Valley	Weslaco	Texas
United States	University of Kansas - Wichita	Wichita	Kansas
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	Spinal Pain and Medical Rehab, PC	Yonkers	New York

Sponsors (3)

Lead Sponsor	Collaborator
Susanna Naggie, MD	National Center for Advancing Translational Sciences (NCATS), Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to sustained recovery in Days	Time to sustained recovery was the number of days between receipt of study drug and the third of 3 consecutive days without symptoms. Participants who died, by definition, did not recover regardless of reported symptom freedom. The reported summary is the median survival time. The overall effect of each study drug versus matching placebo will be quantified using one of these two primary endpoints, which will be defined and documented per study drug appendix prior to the initial IA: clinical events (hospitalization or death) or time to recovery. The other will be evaluated as a secondary endpoint.	Up to 28 days
Primary	Number of Participants With Hospitalization or Death	The overall effect of each study drug versus matching placebo will be quantified using one of these two primary endpoints, which will be defined and documented per study drug appendix prior to the initial IA: clinical events (hospitalization or death) or time to recovery. The other will be evaluated as a secondary endpoint.	Up to 28 days
Secondary	Time to sustained recovery in Days	(If not evaluated as primary endpoint for the given study drug appendix) Time to sustained recovery was the number of days between receipt of study drug and the third of 3 consecutive days without symptoms. Participants who died, by definition, did not recover regardless of reported symptom freedom. The reported summary is the median survival time. The overall effect of each study drug versus matching placebo will be quantified using one of these two primary endpoints, which will be defined and documented per study drug appendix prior to the initial IA: clinical events (hospitalization or death) or time to recovery. The other will be evaluated as a secondary endpoint.	Up to 28 days
Secondary	Number of Participants With Hospitalization or Death	(If not evaluated as primary endpoint for the given study drug appendix)	Up to 28 days
Secondary	Number of Participants With Mortality		Up to 28 days
Secondary	Time to mortality	Time to mortality was the number of days between drug receipt and death.	Up to 28 days
Secondary	Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death		Up to 28 days
Secondary	Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7.	COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.	Day 7
Secondary	Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14.	COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.	Day 14
Secondary	Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28.	COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.	Day 28
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Physical Function	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a higher score correlates to better outcome for physical function.	Day 7, 14, 28, 90, 120, and 180
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Fatigue	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for fatigue.	Day 7, 14, 28, 90, 120, and 180
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Pain	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for pain.	Day 7, 14, 28, 90, 120, and 180
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Depression	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domain with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for depression.	Day 7, 14, 28, 90, 120, and 180
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Anxiety	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for anxiety.	Day 7, 14, 28, 90, 120, and 180
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Social	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a higher score correlates to better outcome for social roles and activities.	Day 7, 14, 28, 90, 120, and 180
Secondary	Quality of Life (QOL) as measured by the PROMIS-29 - Sleep	The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for sleep.	Day 7, 14, 28, 90, 120, and 180
Secondary	Time Unwell in Days as Measured by the Symptom and Clinical Event Scale	The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). Time unwell was the portion of follow-up (in days) that a participant was symptomatic, hospitalized, or deceased. The quantity is estimated from a Bayesian longitudinal ordinal regression model with covariate adjustment and weakly informative priors.	Up to 14 days
Secondary	Mean Days Benefit as Measured by the Symptom and Clinical Event Scale	The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). The cumulative benefit of treatment A is the probability of experiencing a better outcome on treatment A compared to treatment B, summed over the days of follow-up. The difference between the cumulative benefit of treatment A and the cumulative benefit of treatment B is known as the difference in days benefit. Measure of dispersion is 95% credible interval.	Up to 14 days