Trial Outcomes & Findings for COVID-OUT: Early Outpatient Treatment for SARS-CoV-2 Infection (COVID-19) (NCT NCT04510194)

Results Overview

Clinical progression, defined as Emergency department visit for any COVID-19 related symptom (including hospitalization or death) or decrease in O2 saturation (\<=93% on room air, or need for supplemental oxygen to maintain an O2 saturation \<=93%)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1323 participants

Primary outcome timeframe

14 Days

Results posted on

2026-04-24

Participant Flow

This is a factorial trial.

Participant milestones

Participant milestones
Measure	Randomization Arm - Metformin Only Participants in this arm will receive metformin and the ivermectin or fluvoxamine placebo.	Randomization Arm - Placebo Participants in this arm will receive the metformin placebo and the ivermectin or fluvoxamine placebo.	Randomization Arm - Ivermectin Only Participants in this arm will receive ivermectin and the metformin placebo.	Randomization Arm - Fluvoxamine Only Participants in this arm will receive fluvoxamine and the metformin placebo.	Randomization Arm - Metformin and Fluvoxamine Participants in this arm will receive metformin and fluvoxamine.	Randomization Arm - Metformin and Ivermectin Participants in this arm will receive metformin and ivermectin.
Overall Study STARTED	284	295	206	159	175	204
Overall Study COMPLETED	278	291	206	156	173	201
Overall Study NOT COMPLETED	6	4	0	3	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

COVID-OUT: Early Outpatient Treatment for SARS-CoV-2 Infection (COVID-19)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomization Arm - Metformin Only n=284 Participants Participants in this arm will receive metformin and the ivermectin or fluvoxamine placebo	Randomization Arm - Placebo n=295 Participants Participants in this arm will receive the metformin placebo and the ivermectin or fluvoxamine placebo.	Randomization Arm - Ivermectin Only n=206 Participants Participants in this arm will receive ivermectin and the metformin placebo.	Randomization Arm - Fluvoxamine Only n=159 Participants Participants in this arm will receive fluvoxamine and the metformin placebo.	Randomization Arm - Metformin and Fluvoxamine n=175 Participants Participants in this arm will receive metformin and fluvoxamine.	Randomization Arm - Metformin and Ivermectin n=204 Participants Participants in this arm will receive metformin and ivermectin.	Total n=1323 Participants Total of all reporting groups
Age, Continuous	46 years n=2 Participants	42 years n=1 Participants	48 years n=3 Participants	46 years n=24 Participants	46 years n=2 Participants	46 years n=2 Participants	46 years n=2 Participants
Sex: Female, Male Female	168 Participants n=2 Participants	187 Participants n=1 Participants	108 Participants n=3 Participants	87 Participants n=24 Participants	83 Participants n=2 Participants	108 Participants n=2 Participants	741 Participants n=2 Participants
Sex: Female, Male Male	116 Participants n=2 Participants	108 Participants n=1 Participants	98 Participants n=3 Participants	72 Participants n=24 Participants	92 Participants n=2 Participants	96 Participants n=2 Participants	582 Participants n=2 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=2 Participants	4 Participants n=1 Participants	4 Participants n=3 Participants	4 Participants n=24 Participants	1 Participants n=2 Participants	1 Participants n=2 Participants	18 Participants n=2 Participants
Race (NIH/OMB) Asian	7 Participants n=2 Participants	9 Participants n=1 Participants	6 Participants n=3 Participants	5 Participants n=24 Participants	4 Participants n=2 Participants	7 Participants n=2 Participants	38 Participants n=2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=2 Participants	2 Participants n=1 Participants	0 Participants n=3 Participants	0 Participants n=24 Participants	1 Participants n=2 Participants	1 Participants n=2 Participants	5 Participants n=2 Participants
Race (NIH/OMB) Black or African American	20 Participants n=2 Participants	15 Participants n=1 Participants	12 Participants n=3 Participants	13 Participants n=24 Participants	14 Participants n=2 Participants	13 Participants n=2 Participants	87 Participants n=2 Participants
Race (NIH/OMB) White	213 Participants n=2 Participants	238 Participants n=1 Participants	151 Participants n=3 Participants	125 Participants n=24 Participants	141 Participants n=2 Participants	154 Participants n=2 Participants	1022 Participants n=2 Participants
Race (NIH/OMB) More than one race	10 Participants n=2 Participants	4 Participants n=1 Participants	5 Participants n=3 Participants	4 Participants n=24 Participants	2 Participants n=2 Participants	5 Participants n=2 Participants	30 Participants n=2 Participants
Race (NIH/OMB) Unknown or Not Reported	29 Participants n=2 Participants	23 Participants n=1 Participants	28 Participants n=3 Participants	8 Participants n=24 Participants	12 Participants n=2 Participants	23 Participants n=2 Participants	123 Participants n=2 Participants

PRIMARY outcome

Timeframe: 14 Days

Clinical progression, defined as Emergency department visit for any COVID-19 related symptom (including hospitalization or death) or decrease in O2 saturation (\<=93% on room air, or need for supplemental oxygen to maintain an O2 saturation \<=93%)

Outcome measures

Outcome measures
Measure	Active Metformin n=652 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=653 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=407 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=391 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=329 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=321 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
Clinical Progression to Severe Covid	154 Participants	179 Participants	105 Participants	96 Participants	79 Participants	80 Participants

SECONDARY outcome

Timeframe: 14 days

Emergency department visit for any COVID-19 related symptom (including hospitalization or death), active relative to placebo

Outcome measures

Outcome measures
Measure	Active Metformin n=652 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=653 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=407 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=391 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=329 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=321 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
Clinical Progression to Severe Covid	27 Participants	48 Participants	23 Participants	16 Participants	18 Participants	15 Participants

SECONDARY outcome

Timeframe: 28 days

Count of participants with clinical progression to Hospitalization, Death

Outcome measures

Outcome measures
Measure	Active Metformin n=596 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=601 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=374 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=356 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=299 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=293 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
Progression	8 Participants	19 Participants	4 Participants	5 Participants	6 Participants	5 Participants

SECONDARY outcome

Timeframe: 14 days

Defined by adding the symptom score for each individual symptom on the "Daily Symptom Scale Recommended by FDA For Industry." Each symptom on the scale had an answer option ranging from 0 to 3. They corresponded to 0= no symptom; 1=mild symptom; 2=moderate symptom; 3=severe symptom. The range for the total score is 0 to 42 (14 symptoms x 3). The data presented here are the unadjusted mean (SD) for the total symptom score on Day 14.

Outcome measures

Outcome measures
Measure	Active Metformin n=652 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=653 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=407 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=391 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=329 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=321 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
Maximum Symptom Severity	3.48 total score Standard Deviation 4.0	3.73 total score Standard Deviation 4.29	3.45 total score Standard Deviation 4.12	3.85 total score Standard Deviation 4.28	3.53 total score Standard Deviation 4.24	3.96 total score Standard Deviation 4.46

SECONDARY outcome

Timeframe: 28 days

Progression to Hospitalization or Ventilation by Day 28

Outcome measures

Outcome measures
Measure	Active Metformin n=596 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=601 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=374 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=356 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=299 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=293 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
Clinical Deterioration: Hospital and Vent >3days	7 Participants	18 Participants	3 Participants	5 Participants	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Day5-Day10

Count of participants with no detectable viral load on Day 10.

Outcome measures

Outcome measures
Measure	Active Metformin n=504 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=495 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=319 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=293 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=248 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=240 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
Laboratory Outcome Study	72 Participants	112 Participants	53 Participants	45 Participants	44 Participants	42 Participants

SECONDARY outcome

Timeframe: 14 days

Population: 1,323 participants randomized into 6 arms (284+206+159+204+175+295=1,323) Those 1,323 contributed to 3 randomized comparisons: The Participant Flow Module reflects the 3 randomized comparisons that were possible with the 1,323 individuals randomized. For the study drug discontinuation, it is best to report within the 6 randomization arms.

Study drug discontinuation (total interrupted - total restarted), per treatment allocation. Per treatment allocation means that these counts are not per randomized comparison.

Outcome measures

Outcome measures
Measure	Active Metformin n=284 Participants This group is made up of all participants in the three randomization arms that received active metformin.	Metformin Placebo n=295 Participants This group is made up of all participants in the three randomization arms that received metformin placebo.	Active Ivermectin n=206 Participants This group is made up of the two randomization arms that received ivermectin.	Ivermectin Placebo n=159 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.	Active Fluvoxamine n=175 Participants This group if made up of the two randomization arms that received fluvoxamine.	Fluvoxamine Placebo n=204 Participants This group is made up of the two randomization arms that did not receive fluvoxamine or ivermectin.
All-cause Study Medicine Discontinuation	56 Participants	49 Participants	25 Participants	32 Participants	50 Participants	29 Participants

SECONDARY outcome

Timeframe: Day 300

Proportion of participants with long-covid syndrome, PASC (post-acute sequelae of SARS-CoV-2 infection)