NCT04885530

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10,956

participants targeted

Target at P75+ for phase_3 covid19

Timeline
Completed

Started Jun 2021

Longer than P75 for phase_3 covid19

Geographic Reach
1 country

110 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 30, 2021

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 13, 2021

Completed
26 days until next milestone

Study Start

First participant enrolled

June 8, 2021

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 29, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 29, 2024

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

November 17, 2025

Completed
Last Updated

November 17, 2025

Status Verified

November 1, 2025

Enrollment Period

2.9 years

First QC Date

April 30, 2021

Results QC Date

April 21, 2025

Last Update Submit

November 3, 2025

Conditions

Keywords

SARS-CoV-2COVID-19ivermectinPlaceboDuke University Health SystemOutcomesDuke Clinical Research InstitutefluticasonefluvoxamineACTIV 6ACTIVmontelukastmetformin

Outcome Measures

Primary Outcomes (1)

  • Total Number of Participants Randomized Within Each Appendix

    Total number of participants randomized within each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT ID.

    Up to approximately 2 years 10 months

Study Arms (14)

Arm A - Ivermectin 400

EXPERIMENTAL

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.

Drug: Ivermectin

Arm A - Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Arm B - Fluvoxamine

EXPERIMENTAL

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

Drug: Fluvoxamine

Arm B- Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Arm C - Fluticasone

EXPERIMENTAL

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.

Drug: Fluticasone

Arm C - Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Arm D - Ivermectin 600

EXPERIMENTAL

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.

Drug: Ivermectin

Arm D - Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Arm E - Fluvoxamine 100

EXPERIMENTAL

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.

Drug: Fluvoxamine

Arm E - Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Arm F - Montelukast

EXPERIMENTAL

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

Drug: Montelukast

Arm F - Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Arm G - Metformin

EXPERIMENTAL

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.

Drug: Metformin

Arm G - Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

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.

Also known as: Ivermectin Tablets
Arm A - Ivermectin 400Arm D - Ivermectin 600

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.

Also known as: Fluvoxamine Maleate Tablets
Arm B - FluvoxamineArm E - Fluvoxamine 100

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.

Also known as: Fluticasone Furoate
Arm C - Fluticasone
PlaceboOTHER

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 A - PlaceboArm B- PlaceboArm C - PlaceboArm D - PlaceboArm E - PlaceboArm F - PlaceboArm G - Placebo

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 - Montelukast

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 - Metformin

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (110)

Chandler Regional Medical Center

Chandler, Arizona, 85224, United States

Location

Lamb Health, LLC

Gilbert, Arizona, 85298, United States

Location

First Care Medical Clinic

Mesa, Arizona, 85203, United States

Location

Trident Health Center

Peoria, Arizona, 85382, United States

Location

University of Arkansas Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Assuta Family Medical Group APMC

North Hollywood, California, 91606, United States

Location

Stanford

Palo Alto, California, 94304, United States

Location

Olive View - UCLA Medical Center

Sylmar, California, 91342, United States

Location

Doctors Medical Group of Colorado Springs, P.C.

Colorado Springs, Colorado, 80917, United States

Location

Pine Ridge Family Medicine Inc.

Colorado Springs, Colorado, 80924, United States

Location

Tabitha B. Fortt, M.D., LLC

Stamford, Connecticut, 06905, United States

Location

George Washington University Hospital

Washington D.C., District of Columbia, 20037, United States

Location

Arena Medical Group

Deerfield Beach, Florida, 33441, United States

Location

Lupus Foundation of Gainesville

Gainesville, Florida, 32606, United States

Location

University of Florida Health

Gainesville, Florida, 32611, United States

Location

L and A Morales Healthcare, Inc

Hialeah, Florida, 33012, United States

Location

University of Florida-JAX-ASCENT

Jacksonville, Florida, 32209, United States

Location

AMRON Vitality and Wellness Center, LLC

Jacksonville, Florida, 32244, United States

Location

Sunshine Walk In Clinic

Lake Mary, Florida, 32746, United States

Location

Lakeland Regional Medical Center

Lakeland, Florida, 33805, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Well Pharma Medical Research

Miami, Florida, 33173, United States

Location

The Angel Medical Research Corporation

Miami Lakes, Florida, 33016, United States

Location

Innovation Clinical Trials Inc.

Palmetto Bay, Florida, 33157, United States

Location

Lice Source Services Plantation

Plantation, Florida, 33313, United States

Location

Premier Health

St. Petersburg, Florida, 33707, United States

Location

Tallahassee Memorial Hospital

Tallahassee, Florida, 32308, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

UF Health Precision Health Research

The Villages, Florida, 32159, United States

Location

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Emory Healthcare

Atlanta, Georgia, 30322, United States

Location

Essential Medical Care, Inc.

College Park, Georgia, 30349, United States

Location

Clincept, LLC

Columbus, Georgia, 31904, United States

Location

HOPE Clinical Research and Wellness

Conyers, Georgia, 30094, United States

Location

David Kavtaradze MD, Inc.

Cordele, Georgia, 31015, United States

Location

Elite Family Practice

Douglasville, Georgia, 30134, United States

Location

Christ the King Health Care, P.C.

Loganville, Georgia, 30052, United States

Location

Miller Family Practice, LLC

Macon, Georgia, 31201, United States

Location

Northwestern Univesity

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Olivo Wellness Medical Center

Chicago, Illinois, 60618, United States

Location

NorthShore Medical Group

Evanston, Illinois, 60201, United States

Location

Advanced Medical Care, Ltd

Lake Zurich, Illinois, 60047, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Franciscan Health Michigan City

Michigan City, Indiana, 46360, United States

Location

Del Pilar Medical and Urgent Care

Mishawaka, Indiana, 46545, United States

Location

University of Kansas - Wichita

Wichita, Kansas, 67214, United States

Location

A New Start II, LLC

Central City, Kentucky, 42330, United States

Location

Christus Saint Frances Hospita

Alexandria, Louisiana, 71301, United States

Location

University Medical Center- New Orleans

New Orleans, Louisiana, 70112, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287-1900, United States

Location

Jadestone Clinical Research, LLC

Rockville, Maryland, 20855, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Health Quality Primary Care

Lawrence, Massachusetts, 01843, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Ananda Medical Clinic

Dearborn, Michigan, 48124, United States

Location

GFC of Southeastern Michigan, PC

Detroit, Michigan, 48202, United States

Location

Romancare Health Services

Detroit, Michigan, 48206, United States

Location

Essentia Health

Duluth, Minnesota, 55805, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Missouri - Columbia

Columbia, Missouri, 65212, United States

Location

Comprehensive Pain Management and Endocrinology

Henderson, Nevada, 89052, United States

Location

Focus Clinical Research Solutions

Bayonne, New Jersey, 07002, United States

Location

Raritan Bay Primary Care & Cardiology Associates

Matawan, New Jersey, 07747, United States

Location

G&S Medical Associates, LLC

Paterson, New Jersey, 07514, United States

Location

Mediversity Healthcare

Turnersville, New Jersey, 08012, United States

Location

Christus St. Vincent Regional Medical Center

Santa Fe, New Mexico, 87505, United States

Location

Geriatrics and Medical Associates

Clinton, New York, 13323, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Spinal Pain and Medical Rehab, PC

Yonkers, New York, 10701, United States

Location

Vaidya MD PLLC

Clayton, North Carolina, 27520, United States

Location

Maria Medical Center, PLLC

Dunn, North Carolina, 28334, United States

Location

Duke Clinical Research Institute

Durham, North Carolina, 27701, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Lapis Clinical Research

Mooresville, North Carolina, 28117, United States

Location

Superior Clinical Research

Smithfield, North Carolina, 27577, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27151, United States

Location

Diabetes and Endocrinology Assoc. of Stark County

Canton, Ohio, 44718, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

TriHealth, Inc

Montgomery, Ohio, 45242, United States

Location

The Heart and Medical Center

Durant, Oklahoma, 74701, United States

Location

Hugo Medical clinic

Hugo, Oklahoma, 74743, United States

Location

Ascension St. John

Tulsa, Oklahoma, 74104, United States

Location

Bucks County Clinical Research

Morrisville, Pennsylvania, 19067, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Clinical Trials Center of Middle TN

Franklin, Tennessee, 37067, United States

Location

Rapha Family Wellness

Hendersonville, Tennessee, 37075, United States

Location

Medical Specialists of Knoxville

Knoxville, Tennessee, 37938, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Express Family Clinic

Allen, Texas, 75013, United States

Location

DHR Health Institute for Research

Edinburg, Texas, 78539, United States

Location

Texas Tech University Health Sciences Center

El Paso, Texas, 79905, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Texas Health Physicians Group

Fort Worth, Texas, 76107, United States

Location

Highlands Medical Associates, P.A.

Highlands, Texas, 77562, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Family Practice Doctors P.A.

Humble, Texas, 77338, United States

Location

Texas Health Physicians Group

Irving, Texas, 75039, United States

Location

Kintex Group Texas LLC, DBA Activian Clinical Research

Kingwood, Texas, 77339, United States

Location

University Diagnostics and Treatment Clinic

Pasadena, Texas, 77504, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

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

Sugar Land, Texas, 77479, United States

Location

University of Texas Rio Grande Valley

Weslaco, Texas, 78596, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Providence Medical Research Center

Spokane, Washington, 99204, United States

Location

Related Publications (15)

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

COVID-19

Interventions

IvermectinFluvoxamineFluticasonefluticasone furoatemontelukastMetformin

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

MacrolidesPolyketidesLactonesOrganic ChemicalsOximesHydroxylaminesAminesAndrostadienesAndrostenesAndrostanesSteroidsFused-Ring CompoundsPolycyclic CompoundsBiguanidesGuanidinesAmidines

Results Point of Contact

Title
Susanna Naggie, MD, MHS, FIDSA
Organization
Duke University

Study Officials

  • Susanna Naggie, MD

    Duke Clinical Research Institute

    PRINCIPAL INVESTIGATOR
  • Adrian Hernandez, MD

    Duke Clinical Research Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Double-Blind, Placebo-Controlled, Randomized Trial
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

April 30, 2021

First Posted

May 13, 2021

Study Start

June 8, 2021

Primary Completion

April 29, 2024

Study Completion

April 29, 2024

Last Updated

November 17, 2025

Results First Posted

November 17, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

We will share this data after it has been de-identified. We will share data beginning around 6 months after publication and for up to 36 months afterward. Access will only be shared with those who have obtained prior IRB approval to be able to access this data.

Shared Documents
SAP, CSR
Time Frame
Up to 36 months after publication
Access Criteria
Interested investigators will need to seek prior IRB approval before access to any data is granted.

Locations