NCT05736861

ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivermectin 400)

Completed Phase 3 Results posted Last updated 13 June 2023

What this trial tests

Phase 3 trial testing Ivermectin in Covid19 in 1,800 participants. Completed in 16 May 2022.

Timeline

8 June 2021

Primary endpoint
15 March 2022

16 May 2022

Quick facts

Lead sponsor	Susanna Naggie, MD
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	1,800
Start date	8 June 2021
Primary completion	15 March 2022
Estimated completion	16 May 2022
Sites	87 locations across United States

Drugs / interventions tested

• Ivermectin (ivermectin) — full drug profile →
• Placebo

Conditions studied

• Covid19 — all drugs for Covid19 →

Sponsor

Susanna Naggie, MD

Who can join

30 and older, any sex, with Covid19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Sustained Recovery in Days Primary · 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.

Group	Value	95% CI
Arm A - Ivermectin 400	12	11 – 13
Arm A - Placebo	13	12 – 14

Number of Participants With Hospitalization or Death Secondary · Up to 28 days

Group	Value	95% CI
Arm A - Ivermectin 400	10
Arm A - Placebo	9

Number of Participants With Mortality Secondary · Up to 28 days

Group	Value	95% CI
Arm A - Ivermectin 400	1
Arm A - Placebo	0

Time to Mortality Secondary · Up to 28 days

Time to mortality was the number of days between drug receipt and death.

Group	Value	95% CI
Arm A - Ivermectin 400	NA	NA – NA
Arm A - Placebo	NA	NA – NA

Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death Secondary · Up to 28 days

Group	Value	95% CI
Arm A - Ivermectin 400	32
Arm A - Placebo	28

Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 Secondary · 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.

Group	Value	95% CI
Arm A - Ivermectin 400	45
Arm A - Placebo	51
Arm A - Ivermectin 400	708
Arm A - Placebo	646
Arm A - Ivermectin 400	53
Arm A - Placebo	68
Arm A - Ivermectin 400	0
Arm A - Placebo	1

Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 Secondary · 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.

Group	Value	95% CI
Arm A - Ivermectin 400	52
Arm A - Placebo	60
Arm A - Ivermectin 400	722
Arm A - Placebo	664
Arm A - Ivermectin 400	28
Arm A - Placebo	38
Arm A - Ivermectin 400	0
Arm A - Placebo	1

Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 Secondary · 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.

Group	Value	95% CI
Arm A - Ivermectin 400	56
Arm A - Placebo	59
Arm A - Ivermectin 400	718
Arm A - Placebo	682
Arm A - Ivermectin 400	19
Arm A - Placebo	18
Arm A - Ivermectin 400	0
Arm A - Placebo	1

Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function Secondary · 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 7

Group	Value	95% CI
Arm A - Ivermectin 400	19	16 – 20
Arm A - Placebo	19	16 – 20

Day 14

Group	Value	95% CI
Arm A - Ivermectin 400	20	18 – 20
Arm A - Placebo	20	18 – 20

Day 28

Group	Value	95% CI
Arm A - Ivermectin 400	20	20 – 20
Arm A - Placebo	20	20 – 20

Day 90

Group	Value	95% CI
Arm A - Ivermectin 400	20	20 – 20
Arm A - Placebo	20	20 – 20

Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue Secondary · 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 7

Group	Value	95% CI
Arm A - Ivermectin 400	9	7 – 13
Arm A - Placebo	9	7 – 13

Day 14

Group	Value	95% CI
Arm A - Ivermectin 400	7	4 – 9
Arm A - Placebo	7	4 – 9

Day 28

Group	Value	95% CI
Arm A - Ivermectin 400	5	4 – 8
Arm A - Placebo	5	4 – 8

Day 90

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 8
Arm A - Placebo	4	4 – 8

Quality of Life (QOL) as Measured by the PROMIS-29 - Pain Secondary · 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 7

Group	Value	95% CI
Arm A - Ivermectin 400	5	4 – 9
Arm A - Placebo	5	4 – 8

Day 14

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 7
Arm A - Placebo	4	4 – 7

Day 28

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 5
Arm A - Placebo	4	4 – 4

Day 90

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 4
Arm A - Placebo	4	4 – 4

Quality of Life (QOL) as Measured by the PROMIS-29 - Depression Secondary · 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 7

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 6
Arm A - Placebo	4	4 – 6

Day 14

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 5
Arm A - Placebo	4	4 – 5

Day 28

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 5
Arm A - Placebo	4	4 – 5

Day 90

Group	Value	95% CI
Arm A - Ivermectin 400	4	4 – 5
Arm A - Placebo	4	4 – 5

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 90 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A - Ivermectin 400

Serious: 13/817 (2%)

Deaths: 1/817

Arm A - Placebo

Serious: 17/774 (2%)

Deaths: 0/774

Serious adverse events (18 terms)

Reaction	System	Arm A - Ivermectin 400	Arm A - Placebo
COVID-19 pneumonia	Infections and infestations	—	—
COVID-19 pneumonia aggravated	Infections and infestations	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Venous thromboembolism	Vascular disorders	—	—
Bacteremia, with signs and symptoms	Infections and infestations	—	—
Pneumonia due to Staphylococcus	Infections and infestations	—	—
Pneumonia due to Streptococcus, group b	Infections and infestations	—	—
Viral bronchopneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Diplopia	Eye disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Acute Cholecystitis	Hepatobiliary disorders	—	—
Coronary vasospasm	Vascular disorders	—	—
COVID-19 pneumonia worsening	Infections and infestations	—	—
Death due to COVID-19	Infections and infestations	—	—
Opthalmic migraine	Eye disorders	—	—
Pneumonia due to COVID-19 virus	Infections and infestations	—	—
Upper GI bleed	Vascular disorders	—	—
Worsening of covid-19 pneumonia	Infections and infestations	—	—

Other adverse events (28 terms — click to expand)

Reaction	System	Arm A - Ivermectin 400	Arm A - Placebo
Accelerated hair loss	Skin and subcutaneous tissue disorders	—	—
Bladder infection	Infections and infestations	—	—
Blood pressure raised	Investigations	—	—
Chest tightness	General disorders	—	—
Confusion	Nervous system disorders	—	—
COVID-19 pneumonia	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—
Dyspnea	Cardiac disorders	—	—
Hair loss	Skin and subcutaneous tissue disorders	—	—
Heartburn	Gastrointestinal disorders	—	—
Hepatic steatosis	Metabolism and nutrition disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Insomnia	Nervous system disorders	—	—
Interstitial pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Migraine with aura	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Nausea and emesis	Gastrointestinal disorders	—	—
Pain in limb	Musculoskeletal and connective tissue disorders	—	—
Palpitations	Cardiac disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Seasonal Allergies	Immune system disorders	—	—
Shoulder dislocation	Injury, poisoning and procedural complications	—	—
Sinus bradycardia	Cardiac disorders	—	—
Sinus infection	Infections and infestations	—	—
Splenomegaly	Blood and lymphatic system disorders	—	—
Suspected Covid-19	Infections and infestations	—	—
Tiredness	General disorders	—	—
Vomiting	Gastrointestinal disorders	—	—

Most-reported serious reactions: COVID-19 pneumonia, COVID-19 pneumonia aggravated, Pulmonary embolism, Venous thromboembolism, Bacteremia, with signs and symptoms, Pneumonia due to Staphylococcus, Pneumonia due to Streptococcus, group b, Viral bronchopneumonia.

Data from ClinicalTrials.gov NCT05736861 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Quantitative assessment of the impact of standard agreement templates on multisite clinical trial start up time.
   Lawrence CE, Bruce VNM, Salberg LD, Edwards T, et al · · 2023 · cited 9× · PMID 37830004 · DOI 10.1017/cts.2023.622
2. Repurposed Medicines for Viruses With Epidemic or Pandemic Potential: A Horizon Scan.
   Akinbolade S, Potter R, Inskip A, Nesworthy J, et al · · 2026 · PMID 42149126 · DOI 10.1002/prp2.70271