ACTIV-6: COVID-19 Study of Repurposed Medications

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.

Timeline

Start

2021-06-08

Primary completion

2024-04-29

Completion

2024-04-29

Publications

• 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.

Drugs

Indications