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 tomoderate COVID-19. Participants will receive either study drug or placebo. Participantswill self-report any new or worsening symptoms or medical events experienced while takingstudy 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 inperson.Prior and current drug arms are listed on clinicaltrials.gov and will be updated with theactivation of any new drug arms. Each study arm will also have its own clinicaltrials.goventry and will include "Pro00107921" in the Unique Protocol ID.
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.
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.
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
Chandler Regional Medical Center
Chandler 5289282, Arizona 5551752, United States
Lamb Health, LLC
Gilbert 5295903, Arizona 5551752, United States
First Care Medical Clinic
Mesa 5304391, Arizona 5551752, United States
Trident Health Center
Peoria 5308480, Arizona 5551752, United States
University of Arkansas Medical Sciences
Little Rock 4119403, Arkansas 4099753, United States
Hoag Memorial Hospital Presbyterian
Newport Beach 5376890, California 5332921, United States
Assuta Family Medical Group APMC
North Hollywood 5377654, California 5332921, United States
Stanford
Palo Alto 5380748, California 5332921, United States
Olive View - UCLA Medical Center
Sylmar 5400784, California 5332921, United States
Doctors Medical Group of Colorado Springs, P.C.
Colorado Springs 5417598, Colorado 5417618, United States
Pine Ridge Family Medicine Inc.
Colorado Springs 5417598, Colorado 5417618, United States
Tabitha B. Fortt, M.D., LLC
Stamford 4843564, Connecticut 4831725, United States
George Washington University Hospital
Washington D.C. 4140963, District of Columbia 4138106, United States
Arena Medical Group
Deerfield Beach 4153071, Florida 4155751, United States
Lupus Foundation of Gainesville
Gainesville 4156404, Florida 4155751, United States
University of Florida Health
Gainesville 4156404, Florida 4155751, United States
L and A Morales Healthcare, Inc
Hialeah 4158476, Florida 4155751, United States
University of Florida-JAX-ASCENT
Jacksonville 4160021, Florida 4155751, United States
AMRON Vitality and Wellness Center, LLC
Jacksonville 4160021, Florida 4155751, United States
Sunshine Walk In Clinic
Lake Mary 4161373, Florida 4155751, United States
Lakeland Regional Medical Center
Lakeland 4161438, Florida 4155751, United States
Jackson Memorial Hospital
Miami 4164138, Florida 4155751, United States
University of Miami
Miami 4164138, Florida 4155751, United States
Well Pharma Medical Research
Miami 4164138, Florida 4155751, United States
The Angel Medical Research Corporation
Miami Lakes 4164186, Florida 4155751, United States
Innovation Clinical Trials Inc.
Palmetto Bay 4167634, Florida 4155751, United States
Lice Source Services Plantation
Plantation 4168782, Florida 4155751, United States
Premier Health
St. Petersburg 4171563, Florida 4155751, United States
Tallahassee Memorial Hospital
Tallahassee 4174715, Florida 4155751, United States
Tampa General Hospital
Tampa 4174757, Florida 4155751, United States
UF Health Precision Health Research
The Villages 4175179, Florida 4155751, United States
Morehouse School of Medicine
Atlanta 4180439, Georgia 4197000, United States
Emory Healthcare
Atlanta 4180439, Georgia 4197000, United States
Essential Medical Care, Inc.
College Park 4188815, Georgia 4197000, United States
Clincept, LLC
Columbus 4188985, Georgia 4197000, United States
HOPE Clinical Research and Wellness
Conyers 4189213, Georgia 4197000, United States
David Kavtaradze MD, Inc.
Cordele 4189423, Georgia 4197000, United States
Elite Family Practice
Douglasville 4191955, Georgia 4197000, United States
Christ the King Health Care, P.C.
Loganville 4206547, Georgia 4197000, United States
Miller Family Practice, LLC
Macon 4207400, Georgia 4197000, United States
Northwestern Univesity
Chicago 4887398, Illinois 4896861, United States
Rush University Medical Center
Chicago 4887398, Illinois 4896861, United States
Olivo Wellness Medical Center
Chicago 4887398, Illinois 4896861, United States
NorthShore Medical Group
Evanston 4891382, Illinois 4896861, United States
Advanced Medical Care, Ltd
Lake Zurich 4899170, Illinois 4896861, United States
Loyola University Medical Center
Maywood 4901514, Illinois 4896861, United States
Franciscan Health Michigan City
Michigan City 4923531, Indiana 4921868, United States
Del Pilar Medical and Urgent Care
Mishawaka 4923670, Indiana 4921868, United States
University of Kansas - Wichita
Wichita 4281730, Kansas 4273857, United States
A New Start II, LLC
Central City 4287450, Kentucky 6254925, United States
Christus Saint Frances Hospita
Alexandria 4314550, Louisiana 4331987, United States
University Medical Center- New Orleans
New Orleans 4335045, Louisiana 4331987, United States
Ochsner Clinic Foundation
New Orleans 4335045, Louisiana 4331987, United States
Johns Hopkins Hospital
Baltimore 4347778, Maryland 4361885, United States
Jadestone Clinical Research, LLC
Rockville 4367175, Maryland 4361885, United States
Boston Medical Center
Boston 4930956, Massachusetts 6254926, United States
Health Quality Primary Care
Lawrence 4941720, Massachusetts 6254926, United States
University of Massachusetts Medical School
Worcester 4956184, Massachusetts 6254926, United States
Ananda Medical Clinic
Dearborn 4990510, Michigan 5001836, United States
GFC of Southeastern Michigan, PC
Detroit 4990729, Michigan 5001836, United States
Romancare Health Services
Detroit 4990729, Michigan 5001836, United States
Essentia Health
Duluth 5024719, Minnesota 5037779, United States
University of Minnesota
Minneapolis 5037649, Minnesota 5037779, United States
University of Missouri - Columbia
Columbia 4381982, Missouri 4398678, United States
Comprehensive Pain Management and Endocrinology
Henderson 5505411, Nevada 5509151, United States
Focus Clinical Research Solutions
Bayonne 5095445, New Jersey 5101760, United States
Raritan Bay Primary Care & Cardiology Associates
Matawan 5100940, New Jersey 5101760, United States
G&S Medical Associates, LLC
Paterson 5102466, New Jersey 5101760, United States
Mediversity Healthcare
Turnersville 4504536, New Jersey 5101760, United States
Christus St. Vincent Regional Medical Center
Santa Fe 5490263, New Mexico 5481136, United States
Geriatrics and Medical Associates
Clinton 5112972, New York 5128638, United States
Weill Cornell Medical College
New York 5128581, New York 5128638, United States
Spinal Pain and Medical Rehab, PC
Yonkers 5145215, New York 5128638, United States
Vaidya MD PLLC
Clayton 4460943, North Carolina 4482348, United States
Maria Medical Center, PLLC
Dunn 4464326, North Carolina 4482348, United States
Duke Clinical Research Institute
Durham 4464368, North Carolina 4482348, United States
Duke University Medical Center
Durham 4464368, North Carolina 4482348, United States
Lapis Clinical Research
Mooresville 4480125, North Carolina 4482348, United States
Superior Clinical Research
Smithfield 4492168, North Carolina 4482348, United States
Wake Forest Baptist Health
Winston-Salem 4499612, North Carolina 4482348, United States
Diabetes and Endocrinology Assoc. of Stark County
Canton 5149222, Ohio 5165418, United States
University of Cincinnati
Cincinnati 4508722, Ohio 5165418, United States
TriHealth, Inc
Montgomery 4518597, Ohio 5165418, United States
The Heart and Medical Center
Durant 4535414, Oklahoma 4544379, United States
Hugo Medical clinic
Hugo 4539145, Oklahoma 4544379, United States
Ascension St. John
Tulsa 4553433, Oklahoma 4544379, United States
Bucks County Clinical Research
Morrisville 5201996, Pennsylvania 6254927, United States
Temple University Hospital
Philadelphia 4560349, Pennsylvania 6254927, United States
University of Pittsburgh
Pittsburgh 5206379, Pennsylvania 6254927, United States
Medical University of South Carolina
Charleston 4574324, South Carolina 4597040, United States
Clinical Trials Center of Middle TN
Franklin 4623560, Tennessee 4662168, United States
Rapha Family Wellness
Hendersonville 4628735, Tennessee 4662168, United States
Medical Specialists of Knoxville
Knoxville 4634946, Tennessee 4662168, United States
Vanderbilt University Medical Center
Nashville 4644585, Tennessee 4662168, United States
Express Family Clinic
Allen 4670300, Texas 4736286, United States
DHR Health Institute for Research
Edinburg 4688275, Texas 4736286, United States
Texas Tech University Health Sciences Center
El Paso 5520993, Texas 4736286, United States
Brooke Army Medical Center
Fort Sam Houston 7267736, Texas 4736286, United States
Texas Health Physicians Group
Fort Worth 4691930, Texas 4736286, United States
Highlands Medical Associates, P.A.
Highlands 4697652, Texas 4736286, United States
University of Texas Health Science Center at Houston
Houston 4699066, Texas 4736286, United States
Family Practice Doctors P.A.
Humble 4699442, Texas 4736286, United States
Texas Health Physicians Group
Irving 4700168, Texas 4736286, United States
Kintex Group Texas LLC, DBA Activian Clinical Research
Kingwood 7534469, Texas 4736286, United States
University Diagnostics and Treatment Clinic
Pasadena 4717782, Texas 4736286, United States
University of Texas Health Science Center at San Antonio
San Antonio 4726206, Texas 4736286, United States
Jeremy W. Szeto, D.O., P.A.
Sugar Land 4734825, Texas 4736286, United States
University of Texas Rio Grande Valley
Weslaco 4740629, Texas 4736286, United States
University of Virginia
Charlottesville 4752031, Virginia 6254928, United States
Providence Medical Research Center
Spokane 5811696, Washington 5815135, United States