ACTIV-6: COVID-19 Study of Repurposed Medications | NCT04885530

ID	Type	Description	Link
3U24TR001608-05W1	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Center for Advancing Translational Sciences (NCATS)	NIH
Vanderbilt University Medical Center	OTHER

Description Module

Detailed 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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ivermectin	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.

Measure	Description	Time Frame
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

Eligibility Module

Name	Affiliation	Role
Susanna Naggie, MD	Duke Clinical Research Institute	Principal Investigator
Adrian Hernandez, MD	Duke Clinical Research Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Chandler Regional Medical Center		Chandler	Arizona	85224	United States
Lamb Health, LLC

PubMed Identifier	Type	Citation	Retractions
41030935	Derived	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.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A - Ivermectin 400	Ivermectin - 7-mg tablets or Placebo 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. 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 5, 2024

Arm/Group Information

ID	Title	Description
BG000	Arm A - Ivermectin 400	Ivermectin - 7-mg tablets or Placebo 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. 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.
BG001	Arm B - Fluvoxamine	Fluvoxamine or Placebo will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days. 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.
BG002	Arm C - Fluticasone	Fluticasone or Placebo 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. 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.
BG003	Arm D - Ivermectin 600	Ivermectin - 7-mg tablets or Placebo 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. 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.
BG004	Arm E - Fluvoxamine 100	Fluvoxamine or Placebo 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. 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.
BG005	Arm F - Montelukast	Montelukast or Placebo will be self-administered orally by each participant at a dose of 10 mg once a day for 14 days. 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.
BG006	Arm G - Metformin	Metformin IR tablets or Placebo 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. 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.
BG007	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Data reported for each substudy/arm separately as some placebo participants were shared among substudies.

Median

Inter-Quartile Range

years

Title	Denominators	Categories
Substudy A	ParticipantsBG0001800 ParticipantsBG0010 ParticipantsBG0020 ParticipantsBG003

Sex/Gender, Customized

Data reported for each substudy/arm separately as some placebo participants were shared among substudies.

Count of Participants

Participants

Title	Denominators	Categories
Substudy A: Sex/Gender	ParticipantsBG0001800 ParticipantsBG0010 ParticipantsBG002

Ethnicity (NIH/OMB)

Data reported for each substudy/arm separately as some placebo participants were shared among substudies.

Count of Participants

Participants

Title	Denominators	Categories
Substudy A	ParticipantsBG0001800 ParticipantsBG0010 ParticipantsBG002

Race/Ethnicity, Customized

Data reported for each substudy/arm separately as some placebo participants were shared among substudies.

Count of Participants

Participants

Title	Denominators	Categories
Substudy A: Race	ParticipantsBG0001800 ParticipantsBG0010 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Individuals who met inclusion criteria and consented for study drug for each study arm. Given that participants were not randomized at this point, one number is reported for each study arm as a whole.

Posted

Count of Participants

Participants

Up to approximately 2 years 10 months

ID	Title	Description
OG000	Arm A - Ivermectin 400	Ivermectin - 7-mg tablets or Placebo 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. 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.
OG001	Arm B - Fluvoxamine	Fluvoxamine or Placebo will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days. 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.
OG002	Arm C - Fluticasone	Fluticasone or Placebo 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. 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.
OG003	Arm D - Ivermectin 600	Ivermectin - 7-mg tablets or Placebo 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. 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.
OG004	Arm E - Fluvoxamine 100	Fluvoxamine or Placebo 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. 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.
OG005	Arm F - Montelukast	Montelukast or Placebo will be self-administered orally by each participant at a dose of 10 mg once a day for 14 days. 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.
OG006	Arm G - Metformin	Metformin IR tablets or Placebo 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. 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.

Units	Counts
Participants	OG0003457 OG0013837 OG0023315 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001800 OG0011331 OG0021407 OG003

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (At Risk)
EG000	Arm A - Ivermectin 400	Ivermectin - 7-mg tablets or Placebo 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. 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.	1,800	1,800	1,800
EG001	Arm B - Fluvoxamine	Fluvoxamine or Placebo will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days. 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.	1,331	1,331	1,331
EG002	Arm C - Fluticasone	Fluticasone or Placebo 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. 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.	1,407	1,407	1,407
EG003	Arm D - Ivermectin 600	Ivermectin - 7-mg tablets or Placebo 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. 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.	1,459	1,459	1,459
EG004	Arm E - Fluvoxamine 100	Fluvoxamine or Placebo 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. 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.	1,208	1,208	1,208
EG005	Arm F - Montelukast	Montelukast or Placebo will be self-administered orally by each participant at a dose of 10 mg once a day for 14 days. 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.	1,453	1,453	1,453
EG006	Arm G - Metformin	Metformin IR tablets or Placebo 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. 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.	3,214	3,214	3,214

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D018942	Macrolides
D061065	Polyketides
D007783	Lactones
D009930	Organic Chemicals
D010091	Oximes
D006898	Hydroxylamines
D000588	Amines
D000730	Androstadienes
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D001645	Biguanides
D006146	Guanidines
D000578	Amidines

ID	Term
D007559	Ivermectin
D016666	Fluvoxamine
D000068298	Fluticasone
C523187	fluticasone furoate
C093875	montelukast
D008687	Metformin