Covid19
Conditions
Keywords
SARS-CoV-2, COVID-19, ivermectin, Placebo, Duke University Health System, Outcomes, Duke Clinical Research Institute, ACTIV 6, ACTIV
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. This protocol was originally registered under NCT04885530. Per recent guidance on reporting master protocol research programs (MPRPs), a separate record for Arm A was created.
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.
Interventions
DRUGIvermectin
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.
OTHERPlacebo
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.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
Vanderbilt University Medical Center
Susanna Naggie, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
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.
Intervention model description
Double-Blind, Placebo-Controlled, Randomized Trial
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
* Prior diagnosis of COVID-19 infection (\> 10 days from screening) * Current or recent (within 10 days of screening) hospitalization * Current use 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\* \[If only one study drug appendix is open at the time of enrollment. If multiple study drug appendices are open, a participant may opt-out of any study drug appendix or be excluded from any study drug appendix based on contraindications listed in the study drug appendix, current use of study drug, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining study drug appendices.\] Arm-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mortality | Up to 28 days | — |
| Time to Mortality | Up to 28 days | Time to mortality was the number of days between drug receipt and death. |
| Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death | Up to 28 days | — |
| 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 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. |
| 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. |
| Number of Participants With Hospitalization 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. |
| 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. |
| 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 - 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. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 817 |
| 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.
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. | 774 |
| Total | 1,591 |
Baseline characteristics
| Characteristic | Arm A - Ivermectin 400 | Arm A - Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47 years | 48 years | 47 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 93 Participants | 70 Participants | 163 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 724 Participants | 704 Participants | 1428 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 11 Participants | 5 Participants | 16 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 16 Participants | 30 Participants |
| Race/Ethnicity, Customized Black, African American, or African | 50 Participants | 53 Participants | 103 Participants |
| Race/Ethnicity, Customized Middle Eastern or North African | 29 Participants | 23 Participants | 52 Participants |
| Race/Ethnicity, Customized More than one race | 19 Participants | 8 Participants | 27 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized None of the above | 25 Participants | 16 Participants | 41 Participants |
| Race/Ethnicity, Customized No response | 12 Participants | 7 Participants | 19 Participants |
| Race/Ethnicity, Customized Prefer not to answer | 14 Participants | 24 Participants | 38 Participants |
| Race/Ethnicity, Customized White | 643 Participants | 619 Participants | 1262 Participants |
| Region of Enrollment United States | 817 Participants | 774 Participants | 1591 Participants |
| Sex/Gender, Customized Sex/Gender Female | 508 Participants | 424 Participants | 932 Participants |
| Sex/Gender, Customized Sex/Gender Male | 309 Participants | 349 Participants | 658 Participants |
| Sex/Gender, Customized Sex/Gender Prefer Not to Answer | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 817 | 0 / 774 |
| other Total, other adverse events | 16 / 817 | 13 / 774 |
| serious Total, serious adverse events | 13 / 817 | 17 / 774 |
Outcome results
Primary
Time to Sustained Recovery in 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.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Ivermectin 400 | Time to Sustained Recovery in Days | 12 days |
| Arm A - Placebo | Time to Sustained Recovery in Days | 13 days |
95% CI: [0.96, 1.17]
Secondary
Mean Days Benefit as Measured by the Symptom and Clinical Event Scale
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.
Time frame: Up to 14 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A - Ivermectin 400 | Mean Days Benefit as Measured by the Symptom and Clinical Event Scale | 3.91 days |
| Arm A - Placebo | Mean Days Benefit as Measured by the Symptom and Clinical Event Scale | 3.31 days |
Comparison: Analysis is exploratory. No hypothesis test or decision rule was evaluated.95% CI: [0.18, 0.99]
Secondary
Number of Participants at Each Score on the COVID Clinical Progression Scale at 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.
Time frame: Day 14
Population: Data not collected on 21 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 1 = No limitation of activities | 722 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 6 = Hospitalized, on intubation and mechanical ventilation | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 2 = Limitation of activities | 28 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 8 = Death | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 0 = No clinical or virological evidence of infection | 52 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 8 = Death | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 0 = No clinical or virological evidence of infection | 60 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 1 = No limitation of activities | 664 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 2 = Limitation of activities | 38 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 3 = Hospitalized, no oxygen therapy | 1 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 1 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 1 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
95% CI: [0.39, 1.13]
Secondary
Number of Participants at Each Score on the COVID Clinical Progression Scale at 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.
Time frame: Day 28
Population: Data not collected on 36 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 1 = No limitation of activities | 718 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 6 = Hospitalized, on intubation and mechanical ventilation | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 0 = No clinical or virological evidence of infection | 56 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 8 = Death | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 2 = Limitation of activities | 19 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 8 = Death | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 0 = No clinical or virological evidence of infection | 59 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 1 = No limitation of activities | 682 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 2 = Limitation of activities | 18 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 3 = Hospitalized, no oxygen therapy | 1 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
95% CI: [0.52, 1.91]
Secondary
Number of Participants at Each Score on the COVID Clinical Progression Scale at 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.
Time frame: Day 7
Population: Data not collected on 9 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 2 = Limitation of activities | 53 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 1 = No limitation of activities | 708 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 6 = Hospitalized, on intubation and mechanical ventilation | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 0 = No clinical or virological evidence of infection | 45 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 5 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 8 = Death | 1 Participants |
| Arm A - Ivermectin 400 | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 8 = Death | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 0 = No clinical or virological evidence of infection | 51 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 1 = No limitation of activities | 646 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 2 = Limitation of activities | 68 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 3 = Hospitalized, no oxygen therapy | 1 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 2 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 1 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm A - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
95% CI: [0.5, 1.13]
Secondary
Number of Participants With Hospitalization or Death
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A - Ivermectin 400 | Number of Participants With Hospitalization or Death | 10 Participants |
| Arm A - Placebo | Number of Participants With Hospitalization or Death | 9 Participants |
95% CI: [0.4, 2.6]
Secondary
Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A - Ivermectin 400 | Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death | 32 Participants |
| Arm A - Placebo | Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death | 28 Participants |
95% CI: [0.6, 1.8]
Secondary
Number of Participants With Mortality
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A - Ivermectin 400 | Number of Participants With Mortality | 1 Participants |
| Arm A - Placebo | Number of Participants With Mortality | 0 Participants |
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 7 | 5 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 14 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 28 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 7 | 5 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 28 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 14 | 4 score on a scale |
Comparison: Day 795% CI: [0.97, 1.47]
Comparison: Day 1495% CI: [0.84, 1.33]
Comparison: Day 2895% CI: [0.95, 1.55]
Comparison: Day 9095% CI: [0.73, 1.19]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 7 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 14 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 28 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 7 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 28 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 14 | 4 score on a scale |
Comparison: Day 795% CI: [0.87, 1.35]
Comparison: Day 1495% CI: [0.96, 1.57]
Comparison: Day 2895% CI: [0.92, 1.54]
Comparison: Day 9095% CI: [0.71, 1.18]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 7 | 9 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 14 | 7 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 28 | 5 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 7 | 9 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 28 | 5 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 14 | 7 score on a scale |
Comparison: Day 795% CI: [0.92, 1.32]
Comparison: Day 1495% CI: [0.83, 1.22]
Comparison: Day 2895% CI: [0.83, 1.24]
Comparison: Day 9095% CI: [0.72, 1.1]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Pain
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 7 | 5 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 28 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 14 | 4 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 90 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 7 | 5 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 14 | 4 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 28 | 4 score on a scale |
Comparison: Day 795% CI: [0.8, 1.2]
Comparison: Day 1495% CI: [0.78, 1.25]
Comparison: Day 2895% CI: [0.86, 1.43]
Comparison: Day 9095% CI: [0.66, 1.12]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 7 | 19 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 14 | 20 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 28 | 20 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 90 | 20 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 90 | 20 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 7 | 19 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 28 | 20 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 14 | 20 score on a scale |
Comparison: Day 795% CI: [0.82, 1.25]
Comparison: Day 1495% CI: [0.78, 1.23]
Comparison: Day 2895% CI: [0.82, 1.41]
Comparison: Day 9095% CI: [0.57, 1.01]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 7 | 10 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 14 | 9 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 28 | 8 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 90 | 8 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 90 | 8 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 7 | 10 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 28 | 9 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Domain | Day 14 | 9 score on a scale |
Comparison: Day 795% CI: [0.88, 1.27]
Comparison: Day 1495% CI: [0.79, 1.14]
Comparison: Day 2895% CI: [0.75, 1.09]
Comparison: Day 9095% CI: [0.93, 1.36]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Social
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.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 7 | 17 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 14 | 20 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 28 | 20 score on a scale |
| Arm A - Ivermectin 400 | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 90 | 20 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 90 | 20 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 7 | 17 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 28 | 20 score on a scale |
| Arm A - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 14 | 20 score on a scale |
Comparison: Day 795% CI: [0.86, 1.26]
Comparison: Day 1495% CI: [0.85, 1.29]
Comparison: Day 2895% CI: [0.85, 1.34]
Comparison: Day 9095% CI: [0.8, 1.28]
Secondary
Time to Mortality
Time to mortality was the number of days between drug receipt and death.
Time frame: Up to 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A - Ivermectin 400 | Time to Mortality | NA days |
| Arm A - Placebo | Time to Mortality | NA days |
Secondary
Time Unwell in Days as Measured by the Symptom and Clinical Event Scale
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.
Time frame: Up to 14 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A - Ivermectin 400 | Time Unwell in Days as Measured by the Symptom and Clinical Event Scale | 10.96 days |
| Arm A - Placebo | Time Unwell in Days as Measured by the Symptom and Clinical Event Scale | 11.45 days |
95% CI: [-0.82, -0.15]