ACTIV-6: COVID-19 Study of Repurposed Medications

NCT ID: NCT04885530

Last Updated: 2025-11-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

10956 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-08

Study Completion Date

2024-04-29

Brief Summary

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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. They will self-report any new or worsening symptoms or medical events they may experience 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 see them 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.

Pro00107921\_A - Arm D (Ivermectin 400) - NCT05736861; Pro00107921\_B - Arm B (Fluvoxamine) - NCT05890586; Pro00107921\_C - Arm C (Fluticasone) - NCT05736874; Pro00107921\_D - Arm D (Ivermectin 600) - NCT05894538; Pro00107921\_E - Arm E (Fluvoxamine 100) - NCT05894564; Pro00107921\_F - Arm F (Montelukast) - NCT05894577; Pro00107921\_G - Arm G (Metformin) - NCT06042855.

Detailed Description

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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.

Conditions

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Covid19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-Blind, Placebo-Controlled, Randomized Trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers
The participant and study teams will know which study drug the participant is allocated to, but will be blinded to study drug versus placebo because they will be matching.

Study Groups

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Arm A - Ivermectin 400

Ivermectin - 7-mg tablets

Participant will be instructed to take a pre-specified number of tablets for 3 consecutive days based on their weight for a daily dose of approximately 300-400 µg/kg.

Group Type EXPERIMENTAL

Ivermectin

Intervention Type DRUG

Each participant will receive a sufficient quantity of 7-mg tablets to be taken as directed based on their weight. The tablets are white, round, biconvex tablets with "123" over the scoring on one side. All packaging will be labeled to indicate that the product is for investigational use.

Arm A - Placebo

Placebo - appearance and size matched to active study drug.

Participant will be instructed to take a pre-specified number of tablets for 3 consecutive days based on their weight, matched to active study drug dosing.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Arm B - Fluvoxamine

Fluvoxamine will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days.

Group Type EXPERIMENTAL

Fluvoxamine

Intervention Type DRUG

Fluvoxamine is a round golden 50 mg tablet that is scored on both sides - one side has "APO" and the other side has "F50" with a partial bisect. All packaging will be labeled to indicate that the product is for investigational use, administered at a dose of 50 mg, twice daily for 10 days.

Arm B- Placebo

Placebo - appearance and size matched to active study drug. Placebo will be self-administered orally by each participant twice a day for 10 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Arm C - Fluticasone

Fluticasone is a self-administered inhaled drug. Participants will self-administer 200 µg (1 blister) of fluticasone once daily for 14 days. After inhaler activation, the powder within the blister is exposed and the participant inhales the study drug through the mouthpiece.

Group Type EXPERIMENTAL

Fluticasone

Intervention Type DRUG

Fluticasone furoate is an inhaled powder drug product composed of fluticasone furoate. It is a synthetic trifluorinated corticosteroid that is insoluble in water. Fluticasone furoate is a white powder and will be provided in a two tone grey inhaler with a mouthpiece cover and separate foil blister strips. The inhaler will be packaged in a moisture-protective foil tray with a desiccant and a peelable lid.All packaging will be labeled to indicate that the product is for investigational use. Participants will self-administer 200 µg (1 blister) of fluticasone furoate once daily for 14 days.

Arm C - Placebo

Placebo is a self-administered by inhalation. Participants will self-administer 1 blister of placebo once daily for 14 days. After inhaler activation, the powder within the blister is exposed and the participant inhales the placebo through the mouthpiece.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Arm D - Ivermectin 600

Ivermectin - 7-mg tablets

Participant will be instructed to take a pre-specified number of tablets for 6 consecutive days based on their weight for a daily dose of approximately 400-600 µg/kg.

Group Type EXPERIMENTAL

Ivermectin

Intervention Type DRUG

Each participant will receive a sufficient quantity of 7-mg tablets to be taken as directed based on their weight. The tablets are white, round, biconvex tablets with "123" over the scoring on one side. All packaging will be labeled to indicate that the product is for investigational use.

Arm D - Placebo

Placebo - appearance and size matched to active study drug.

Participant will be instructed to take a pre-specified number of tablets for 6 consecutive days based on their weight, matched to active study drug dosing.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Arm E - Fluvoxamine 100

Fluvoxamine will be self-administered orally by each participant at a dose of 50 mg twice a day for 1 day, followed by a dose of 100 mg twice a day for 12 days.

Group Type EXPERIMENTAL

Fluvoxamine

Intervention Type DRUG

Fluvoxamine is a round golden 50 mg tablet that is scored on both sides - one side has "APO" and the other side has "F50" with a partial bisect. All packaging will be labeled to indicate that the product is for investigational use, administered at a dose of 50 mg, twice daily for 10 days.

Arm E - Placebo

Placebo - appearance and size matched to active study drug.

Placebo will be self-administered orally by each participant, with number of tablets matched to active study drug dosing.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Arm F - Montelukast

Montelukast will be self-administered orally by each participant at a dose of 10 mg once a day for 14 days.

Group Type EXPERIMENTAL

Montelukast

Intervention Type DRUG

Montelukast sodium is a white to off-white powder. The 10 mg montelukast tablets are beige, rounded square-shaped, biconvex, film-coated tablets. Each tablet contains 10.4 mg of montelukast sodium, which is equivalent to 10 mg montelukast. All packaging will be labeled to indicate that the product is for investigational use.

Arm F - Placebo

Placebo - appearance and size matched to active study drug.

Placebo will be self-administered orally by each participant, with number of tablets matched to active study drug dosing.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Arm G - Metformin

Metformin IR tablets will be self-administered orally according to the following dosing schedule:

* 500 mg on Day 1;
* 500 mg in the morning and 500 mg in the evening on Day 2 through Day 5; and
* 500 mg in the morning and 2 x 500 mg (a total of 1000 mg) in the evening on Day 6 through Day 14.

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

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.

Arm G - Placebo

Placebo - appearance and size matched to active study drug.

Placebo will be self-administered orally by each participant, with number of tablets matched to active study drug dosing.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Interventions

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Ivermectin

Each participant will receive a sufficient quantity of 7-mg tablets to be taken as directed based on their weight. The tablets are white, round, biconvex tablets with "123" over the scoring on one side. All packaging will be labeled to indicate that the product is for investigational use.

Intervention Type DRUG

Fluvoxamine

Fluvoxamine is a round golden 50 mg tablet that is scored on both sides - one side has "APO" and the other side has "F50" with a partial bisect. All packaging will be labeled to indicate that the product is for investigational use, administered at a dose of 50 mg, twice daily for 10 days.

Intervention Type DRUG

Fluticasone

Fluticasone furoate is an inhaled powder drug product composed of fluticasone furoate. It is a synthetic trifluorinated corticosteroid that is insoluble in water. Fluticasone furoate is a white powder and will be provided in a two tone grey inhaler with a mouthpiece cover and separate foil blister strips. The inhaler will be packaged in a moisture-protective foil tray with a desiccant and a peelable lid.All packaging will be labeled to indicate that the product is for investigational use. Participants will self-administer 200 µg (1 blister) of fluticasone furoate once daily for 14 days.

Intervention Type DRUG

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.

Intervention Type OTHER

Montelukast

Montelukast sodium is a white to off-white powder. The 10 mg montelukast tablets are beige, rounded square-shaped, biconvex, film-coated tablets. Each tablet contains 10.4 mg of montelukast sodium, which is equivalent to 10 mg montelukast. All packaging will be labeled to indicate that the product is for investigational use.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Ivermectin Tablets Fluvoxamine Maleate Tablets Fluticasone Furoate

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role collaborator

Susanna Naggie, MD

OTHER

Sponsor Role lead

Responsible Party

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Susanna Naggie, MD

Associate Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Susanna Naggie, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Adrian Hernandez, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

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Chandler Regional Medical Center

Chandler, Arizona, United States

Site Status

Lamb Health, LLC

Gilbert, Arizona, United States

Site Status

First Care Medical Clinic

Mesa, Arizona, United States

Site Status

Trident Health Center

Peoria, Arizona, United States

Site Status

University of Arkansas Medical Sciences

Little Rock, Arkansas, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Assuta Family Medical Group APMC

North Hollywood, California, United States

Site Status

Stanford

Palo Alto, California, United States

Site Status

Olive View - UCLA Medical Center

Sylmar, California, United States

Site Status

Doctors Medical Group of Colorado Springs, P.C.

Colorado Springs, Colorado, United States

Site Status

Pine Ridge Family Medicine Inc.

Colorado Springs, Colorado, United States

Site Status

Tabitha B. Fortt, M.D., LLC

Stamford, Connecticut, United States

Site Status

George Washington University Hospital

Washington D.C., District of Columbia, United States

Site Status

Arena Medical Group

Deerfield Beach, Florida, United States

Site Status

Lupus Foundation of Gainesville

Gainesville, Florida, United States

Site Status

University of Florida Health

Gainesville, Florida, United States

Site Status

L and A Morales Healthcare, Inc

Hialeah, Florida, United States

Site Status

University of Florida-JAX-ASCENT

Jacksonville, Florida, United States

Site Status

AMRON Vitality and Wellness Center, LLC

Jacksonville, Florida, United States

Site Status

Sunshine Walk In Clinic

Lake Mary, Florida, United States

Site Status

Lakeland Regional Medical Center

Lakeland, Florida, United States

Site Status

Jackson Memorial Hospital

Miami, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Well Pharma Medical Research

Miami, Florida, United States

Site Status

The Angel Medical Research Corporation

Miami Lakes, Florida, United States

Site Status

Innovation Clinical Trials Inc.

Palmetto Bay, Florida, United States

Site Status

Lice Source Services Plantation

Plantation, Florida, United States

Site Status

Premier Health

St. Petersburg, Florida, United States

Site Status

Tallahassee Memorial Hospital

Tallahassee, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

UF Health Precision Health Research

The Villages, Florida, United States

Site Status

Morehouse School of Medicine

Atlanta, Georgia, United States

Site Status

Emory Healthcare

Atlanta, Georgia, United States

Site Status

Essential Medical Care, Inc.

College Park, Georgia, United States

Site Status

Clincept, LLC

Columbus, Georgia, United States

Site Status

HOPE Clinical Research and Wellness

Conyers, Georgia, United States

Site Status

David Kavtaradze MD, Inc.

Cordele, Georgia, United States

Site Status

Elite Family Practice

Douglasville, Georgia, United States

Site Status

Christ the King Health Care, P.C.

Loganville, Georgia, United States

Site Status

Miller Family Practice, LLC

Macon, Georgia, United States

Site Status

Northwestern Univesity

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Olivo Wellness Medical Center

Chicago, Illinois, United States

Site Status

NorthShore Medical Group

Evanston, Illinois, United States

Site Status

Advanced Medical Care, Ltd

Lake Zurich, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Franciscan Health Michigan City

Michigan City, Indiana, United States

Site Status

Del Pilar Medical and Urgent Care

Mishawaka, Indiana, United States

Site Status

University of Kansas - Wichita

Wichita, Kansas, United States

Site Status

A New Start II, LLC

Central City, Kentucky, United States

Site Status

Christus Saint Frances Hospita

Alexandria, Louisiana, United States

Site Status

University Medical Center- New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Jadestone Clinical Research, LLC

Rockville, Maryland, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Health Quality Primary Care

Lawrence, Massachusetts, United States

Site Status

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Ananda Medical Clinic

Dearborn, Michigan, United States

Site Status

GFC of Southeastern Michigan, PC

Detroit, Michigan, United States

Site Status

Romancare Health Services

Detroit, Michigan, United States

Site Status

Essentia Health

Duluth, Minnesota, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

Comprehensive Pain Management and Endocrinology

Henderson, Nevada, United States

Site Status

Focus Clinical Research Solutions

Bayonne, New Jersey, United States

Site Status

Raritan Bay Primary Care & Cardiology Associates

Matawan, New Jersey, United States

Site Status

G&S Medical Associates, LLC

Paterson, New Jersey, United States

Site Status

Mediversity Healthcare

Turnersville, New Jersey, United States

Site Status

Christus St. Vincent Regional Medical Center

Santa Fe, New Mexico, United States

Site Status

Geriatrics and Medical Associates

Clinton, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Spinal Pain and Medical Rehab, PC

Yonkers, New York, United States

Site Status

Vaidya MD PLLC

Clayton, North Carolina, United States

Site Status

Maria Medical Center, PLLC

Dunn, North Carolina, United States

Site Status

Duke Clinical Research Institute

Durham, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Lapis Clinical Research

Mooresville, North Carolina, United States

Site Status

Superior Clinical Research

Smithfield, North Carolina, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Diabetes and Endocrinology Assoc. of Stark County

Canton, Ohio, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

TriHealth, Inc

Montgomery, Ohio, United States

Site Status

The Heart and Medical Center

Durant, Oklahoma, United States

Site Status

Hugo Medical clinic

Hugo, Oklahoma, United States

Site Status

Ascension St. John

Tulsa, Oklahoma, United States

Site Status

Bucks County Clinical Research

Morrisville, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Clinical Trials Center of Middle TN

Franklin, Tennessee, United States

Site Status

Rapha Family Wellness

Hendersonville, Tennessee, United States

Site Status

Medical Specialists of Knoxville

Knoxville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Express Family Clinic

Allen, Texas, United States

Site Status

DHR Health Institute for Research

Edinburg, Texas, United States

Site Status

Texas Tech University Health Sciences Center

El Paso, Texas, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

Texas Health Physicians Group

Fort Worth, Texas, United States

Site Status

Highlands Medical Associates, P.A.

Highlands, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Family Practice Doctors P.A.

Humble, Texas, United States

Site Status

Texas Health Physicians Group

Irving, Texas, United States

Site Status

Kintex Group Texas LLC, DBA Activian Clinical Research

Kingwood, Texas, United States

Site Status

University Diagnostics and Treatment Clinic

Pasadena, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Jeremy W. Szeto, D.O., P.A.

Sugar Land, Texas, United States

Site Status

University of Texas Rio Grande Valley

Weslaco, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Providence Medical Research Center

Spokane, Washington, United States

Site Status

Countries

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United States

References

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Bramante CT, Stewart TG, Boulware DR, McCarthy MW, Gao Y, Rothman RL, Mourad A, Thicklin F, Cohen JB, Garcia Del Sol IT, Ruiz-Unger J, Shah NS, Mehta M, Cardona OQ, Scott J, Ginde AA, Castro M, Jayaweera D, Sulkowski M, Gentile N, McTigue K, Felker GM, Collins S, Dunsmore SE, Adam SJ, Lindsell CJ, Hernandez AF, Naggie S; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Metformin on Time to Sustained Recovery in Adults with COVID-19: The ACTIV-6 Randomized Clinical Trial. medRxiv [Preprint]. 2025 Jan 14:2025.01.13.25320485. doi: 10.1101/2025.01.13.25320485.

Reference Type DERIVED
PMID: 41030935 (View on PubMed)

Bramante CT, Stewart TG, Boulware DR, McCarthy MW, Gao Y, Rothman RL, Mourad A, Thicklin F, Cohen JB, Garcia Del Sol IT, Shah NS, Mehta M, Quintero Cardona O, Scott J, Ginde AA, Castro M, Jayaweera D, Sulkowski M, Gentile N, McTigue K, Felker GM, Collins S, Dunsmore SE, Adam SJ, Lindsell CJ, Hernandez AF, Naggie S; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Metformin on the Presence of COVID-19 Symptoms Over 6 Months: The ACTIV-6 Randomized Clinical Trial. medRxiv [Preprint]. 2025 Aug 12:2025.08.08.25333305. doi: 10.1101/2025.08.08.25333305.

Reference Type DERIVED
PMID: 40832427 (View on PubMed)

Bramante CT, Stewart TG, Boulware DR, McCarthy MW, Gao Y, Rothman RL, Mourad A, Thicklin F, Cohen JB, Garcia Del Sol IT, Ruiz-Unger J, Shah NS, Mehta M, Cardona OQ, Scott J, Ginde AA, Castro M, Jayaweera D, Sulkowski M, Gentile N, McTigue K, Felker GM, Collins S, Dunsmore SE, Adam SJ, Lindsell CJ, Hernandez AF, Naggie S; Accelerating COVID-19 Therapeutic Interventions and Vaccines-6 Study Group and Investigators. Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial. JAMA Intern Med. 2025 Sep 1;185(9):1092-1101. doi: 10.1001/jamainternmed.2025.2570.

Reference Type DERIVED
PMID: 40658388 (View on PubMed)

Rothman RL, Stewart TG, Mourad A, Boulware DR, McCarthy MW, Thicklin F, Garcia Del Sol IT, Garcia JL, Bramante CT, Shah NS, Singh U, Williamson JC, Rebolledo PA, Jagannathan P, Schwasinger-Schmidt T, Ginde AA, Castro M, Jayaweera D, Sulkowski M, Gentile N, McTigue K, Felker GM, DeLong A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Hanna GJ, Shenkman E, Hernandez AF, Naggie S, Lindsell CJ; Accelerating COVID-19 Therapeutic Interventions and Vaccines-6 Study Group and Investigators. Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo: The ACTIV-6 Randomized Clinical Trial. JAMA Netw Open. 2024 Oct 1;7(10):e2439332. doi: 10.1001/jamanetworkopen.2024.39332.

Reference Type DERIVED
PMID: 39422912 (View on PubMed)

Rothman RL, Stewart TG, Mourad A, Boulware DR, McCarthy MW, Thicklin F, Garcia Del Sol IT, Garcia JL, Bramante CT, Shah NS, Singh U, Williamson JC, Rebolledo PA, Jagannathan P, Schwasinger-Schmidt T, Ginde AA, Castro M, Jayaweera D, Sulkowski M, Gentile N, McTigue K, Felker GM, DeLong A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Hanna GJ, Shenkman E, Hernandez AF, Naggie S, Lindsell CJ; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial. medRxiv [Preprint]. 2024 May 18:2024.05.16.24307115. doi: 10.1101/2024.05.16.24307115.

Reference Type DERIVED
PMID: 38798524 (View on PubMed)

Stewart TG, Rebolledo PA, Mourad A, Lindsell CJ, Boulware DR, McCarthy MW, Thicklin F, Garcia Del Sol IT, Bramante CT, Lenert LA, Lim S, Williamson JC, Cardona OQ, Scott J, Schwasinger-Schmidt T, Ginde AA, Castro M, Jayaweera D, Sulkowski M, Gentile N, McTigue K, Felker GM, DeLong A, Wilder R, Rothman RL, Collins S, Dunsmore SE, Adam SJ, Hanna GJ, Shenkman E, Hernandez AF, Naggie S; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial. JAMA. 2023 Dec 26;330(24):2354-2363. doi: 10.1001/jama.2023.23363.

Reference Type DERIVED
PMID: 37976072 (View on PubMed)

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators; Naggie S. Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial. medRxiv [Preprint]. 2023 Sep 13:2023.09.12.23295424. doi: 10.1101/2023.09.12.23295424.

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PMID: 37745371 (View on PubMed)

Boulware DR, Lindsell CJ, Stewart TG, Hernandez AF, Collins S, McCarthy MW, Jayaweera D, Gentile N, Castro M, Sulkowski M, McTigue K, Felker GM, Ginde AA, Dunsmore SE, Adam SJ, DeLong A, Hanna G, Remaly A, Thicklin F, Wilder R, Wilson S, Shenkman E, Naggie S; ACTIV-6 Study Group and Investigators. Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19. N Engl J Med. 2023 Sep 21;389(12):1085-1095. doi: 10.1056/NEJMoa2209421.

Reference Type DERIVED
PMID: 37733308 (View on PubMed)

Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Slandzicki AJ, Lim SC, Cohen J, Kavtaradze D, Amon AP, Gabriel A, Gentile N, Felker GM, Jayaweera D, McCarthy MW, Sulkowski M, Rothman RL, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna GJ, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial. JAMA. 2023 Mar 21;329(11):888-897. doi: 10.1001/jama.2023.1650.

Reference Type DERIVED
PMID: 36807465 (View on PubMed)

McCarthy MW, Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Felker GM, Jayaweera D, Sulkowski M, Gentile N, Bramante C, Singh U, Dolor RJ, Ruiz-Unger J, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna G, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2023 Jan 24;329(4):296-305. doi: 10.1001/jama.2022.24100.

Reference Type DERIVED
PMID: 36633838 (View on PubMed)

Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Lim SC, Cohen J, Kavtaradze D, Amon AP, Gabriel A, Gentile N, Felker GM, Rothman RL, Jayaweera D, McCarthy MW, Sulkowski M, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna GJ, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. Effect of Ivermectin 600 mug/kg for 6 days vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial. medRxiv [Preprint]. 2022 Dec 15:2022.12.15.22283488. doi: 10.1101/2022.12.15.22283488.

Reference Type DERIVED
PMID: 36561174 (View on PubMed)

Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Gentile N, Collins S, McCarthy MW, Jayaweera D, Castro M, Sulkowski M, McTigue K, Thicklin F, Felker GM, Ginde AA, Bramante CT, Slandzicki AJ, Gabriel A, Shah NS, Lenert LA, Dunsmore SE, Adam SJ, DeLong A, Hanna G, Remaly A, Wilder R, Wilson S, Shenkman E, Hernandez AF; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) Study Group and Investigators. Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022 Oct 25;328(16):1595-1603. doi: 10.1001/jama.2022.18590.

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PMID: 36269852 (View on PubMed)

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group; Naggie S. Ivermectin for Treatment of Mild-to-Moderate COVID-19 in the Outpatient Setting: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial. medRxiv [Preprint]. 2022 Aug 11:2022.06.10.22276252. doi: 10.1101/2022.06.10.22276252.

Reference Type DERIVED
PMID: 35982669 (View on PubMed)

Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group; Naggie S. Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial. medRxiv [Preprint]. 2022 Aug 11:2022.07.12.22277548. doi: 10.1101/2022.07.12.22277548.

Reference Type DERIVED
PMID: 35982649 (View on PubMed)

Dodds MG, Doyle EB, Reiersen AM, Brown F, Rayner CR. Fluvoxamine for the treatment of COVID-19. Lancet Glob Health. 2022 Mar;10(3):e332. doi: 10.1016/S2214-109X(22)00006-7. No abstract available.

Reference Type DERIVED
PMID: 35180412 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

3U24TR001608-05W1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00107921

Identifier Type: -

Identifier Source: org_study_id

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