ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine)
- Registration Number
- NCT05890586
- Lead Sponsor
- Susanna Naggie, MD
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1331
- 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
- Prior diagnosis of COVID-19 infection (> 10 days from screening)
- Current or recent (within 10 days of screening) hospitalization
- Known allergy/sensitivity or any hypersensitivity to components of the study drug or placebo
- Known contraindication(s) to study drug including prohibited concomitant medications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B - Placebo 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. Arm B - Fluvoxamine Fluvoxamine Fluvoxamine will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days.
- Primary Outcome Measures
Name Time Method Time to Sustained Recovery in Days Up to 28 days Time to sustained recovery was the number of days between receipt of study drug and the third of 3 consecutive days without symptoms. Participants who died, by definition, did not recover regardless of reported symptom freedom. The reported summary is the median survival time.
- Secondary Outcome Measures
Name Time Method Time to Mortality Up to 28 days Time to mortality was the number of days between drug receipt and death.
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 Day 7 COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.
Number of Participants With Hospitalization or Death Up to 28 days Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death Up to 28 days Quality of Life (QOL) as Measured by the PROMIS-29 - Pain Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for pain. Day 90 data to be reported by September 4, 2023.
Number of Participants With Mortality Up to 28 days Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 Day 14 COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for fatigue. Day 90 data to be reported by September 4, 2023.
Time Unwell in Days as Measured by the Symptom and Clinical Event Scale Up to 14 days The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). Time unwell was the portion of follow-up (in days) that a participant was symptomatic, hospitalized, or deceased. The quantity is estimated from a Bayesian longitudinal ordinal regression model with covariate adjustment and weakly informative priors.
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 Day 28 COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a higher score correlates to better outcome for physical function. Day 90 data to be reported by September 4, 2023.
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for depression. Day 90 data to be reported by September 4, 2023.
Quality of Life (QOL) as Measured by the PROMIS-29 - Social Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a higher score correlates to better outcome for social roles and activities. Day 90 data to be reported by September 4, 2023.
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for anxiety.
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Day 7, 14, 28, and 90 The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for sleep. Day 90 data to be reported by September 4, 2023.
Mean Days Benefit as Measured by the Symptom and Clinical Event Scale Up to 14 days The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). The cumulative benefit of treatment A is the probability of experiencing a better outcome on treatment A compared to treatment B, summed over the days of follow-up. The difference between the cumulative benefit of treatment A and the cumulative benefit of treatment B is known as the difference in days benefit. Measure of dispersion is 95% credible interval.
Trial Locations
- Locations (90)
Lamb Health, LLC
🇺🇸Gilbert, Arizona, United States
First Care Medical Clinic
🇺🇸Mesa, Arizona, United States
Trident Health Center
🇺🇸Peoria, Arizona, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Assuta Family Medical Group APMC
🇺🇸North Hollywood, California, United States
Stanford
🇺🇸Palo Alto, California, United States
Doctors Medical Group of Colorado Springs, P.C.
🇺🇸Colorado Springs, Colorado, United States
Pine Ridge Family Medicine Inc.
🇺🇸Colorado Springs, Colorado, United States
Tabitha B. Fortt, M.D., LLC
🇺🇸Stamford, Connecticut, United States
George Washington University Hospital
🇺🇸Washington, District of Columbia, United States
Scroll for more (80 remaining)Lamb Health, LLC🇺🇸Gilbert, Arizona, United States