STOP COVID: A Double-blind, Placebo-controlled Clinical Trial of Fluvoxamine for Symptomatic Individuals With COVID-19 Infection

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT04342663
• Collaborator: (none)
• Enrollment: 152
• Locations: 2
• Arms: 2
• Actual Duration (Months): 8.1
• Patients Per Site: 76
• Patients Per Site Per Month: 9.4

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use.

This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. Only residents of Missouri and Illinois may participate.

Condition or Disease	Intervention/Treatment	Phase
COVID 19; Coronavirus	Drug: Fluvoxamine; Drug: Placebo	Phase 2

Detailed Description

We will consent approximately 152 participants, age 18 and older, who have tested tested positive for COVID-19 and are currently experiencing mild symptoms. All interactions for this study will be conducted remotely by videoconferencing, email, or phone.

Screening: All participants will first complete a pre-screen to see if they may be eligible for the study. Once a participant is confirmed eligible and consented, the study team will send the study materials. These materials will consist of study medication and self-monitoring equipment, including a pregnancy test (for females of childbearing age not using contraception), an oxygen saturation monitor, blood pressure monitor, and thermometer. Once the study team has finalized the screening process, the participant will begin taking the study medication.

RCT: Participants will be randomly assigned (1:1) to take either fluvoxamine or a placebo. This phase of the study will last approximately 15 days and is double-blinded. Participants will take 100mg of fluvoxamine or placebo by mouth three times a day for a daily total of 300mg. They will continue this dose for approximately 15 days. Depending on tolerability, the dose may be adjusted. Participants will also complete short 10-15 minute assessments daily to assess symptoms, results of self-monitoring (including oxygen level, blood pressure, and temperature) and any adverse events.

Open-label Phase: After completing the randomization phase, participants will then participate in an open-label phase (participant will definitely receive fluvoxamine) that will last up to 15 days. Those randomized to placebo will have the opportunity to try fluvoxamine during this time. Those randomized to fluvoxamine will continue this medication while slowly decreasing the drug. The participant may opt out of this phase. The dosage during this time will be 50-100mg two times daily until discontinuing the drug.

Follow-up Phase: We will follow participants for approximately 30 days after the end of the randomized phase. If needed, the study team will review medical records to determine the clinical course of participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled Clinical Trial of Fluvoxamine for Symptomatic Individuals With COVID-19 Infection
• Actual Study Start Date: Apr 10, 2020
• Actual Primary Completion Date: Aug 20, 2020
• Actual Study Completion Date: Dec 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluvoxamine Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days.	Drug: Fluvoxamine; Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.; Other Names: Luvox
Placebo Comparator: Placebo Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days.	Drug: Placebo; Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Met Clinical Worsening [RCT (approximately 15 days)]

   Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.

Secondary Outcome Measures

1. Clinical Deterioration on a Likert-type Scale (0-6) [RCT (approximately 15 days)]

   (0) none; (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. men and woman age 18 and older;

2. Not hospitalized;

3. Has recently tested SARS-CoV-2 (COVID-19 virus) positive.

4. Currently symptomatic with one or more of one or more of the following symptoms: fever, cough, myalgia, mild dyspnea, diarrhea, vomiting, anosmia (inability to smell), ageusia (inability to taste), sore throat.

5. Able to provide informed consent.

Exclusion Criteria:

1. Illness severe enough to require hospitalization or already meeting study's primary endpoint for clinical worsening.

2. Unstable medical comorbidities including, but not limited to: Severe underlying lung disease (COPD on home oxygen, interstitial lung disease, pulmonary hypertension), decompensated cirrhosis, Congestive heart failure (stage 3 or 4 per patient report and/or medical records).

3. Immunocompromised (solid organ transplant, BMT, AIDS, on biologics and/or high dose steroids (>20mg prednisone per day)

4. Unable to provide informed consent (eg moderate-severe dementia diagnosis)

5. Unable to perform the study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BJC	Belleville	Illinois	United States	62220
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Eric J Lenze, MD, Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 21, 2020
• Informed Consent Form - Apr 20, 2020

More Information

Publications

None provided.

• Responsible Party: Eric Lenze, Wallace and Lucille Renard Professor of Psychiatry, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT04342663
• Other Study ID Numbers: 202004023
• First Posted: Apr 13, 2020
• Last Update Posted: Jul 9, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Eric Lenze, Wallace and Lucille Renard Professor of Psychiatry, Washington University School of Medicine: COVID 19; fluvoxamine
• Additional relevant MeSH terms: COVID-19; Fluvoxamine

Study Results

Participant Flow

Arm/Group Title	Fluvoxamine	Placebo
Arm/Group Description	Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days. Fluvoxamine: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.	Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days. Placebo: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.
Period Title: Overall Study
STARTED	80	72
COMPLETED	62	53
NOT COMPLETED	18	19

Baseline Characteristics

Arm/Group Title	Fluvoxamine	Placebo	Total
Arm/Group Description	Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days. Fluvoxamine: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.	Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days. Placebo: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.	Total of all reporting groups
Overall Participants	80	72	152
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	46	45	46
Sex: Female, Male (Count of Participants)
Female	56 70%	53 73.6%	109 71.7%
Male	24 30%	19 26.4%	43 28.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3.8%	2 2.8%	5 3.3%
Not Hispanic or Latino	75 93.8%	66 91.7%	141 92.8%
Unknown or Not Reported	2 2.5%	4 5.6%	6 3.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.4%	1 0.7%
Asian	3 3.8%	1 1.4%	4 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	18 22.5%	20 27.8%	38 25%
White	56 70%	50 69.4%	106 69.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 3.8%	0 0%	3 2%
Co-existing conditions (Count of Participants)
Asthma	17 21.3%	9 12.5%	26 17.1%
Hypertension	15 18.8%	15 20.8%	30 19.7%
Diabetes	9 11.3%	8 11.1%	17 11.2%
High cholesterol	7 8.8%	7 9.7%	14 9.2%
Hyperthyroidism	6 7.5%	6 8.3%	12 7.9%
Anxiety	5 6.3%	1 1.4%	6 3.9%
Arthritis	4 5%	3 4.2%	7 4.6%
Depression	1 1.3%	4 5.6%	5 3.3%
Body mass index category (Count of Participants)
Underweight (<18.5)	1 1.3%	1 1.4%	2 1.3%
Normal (18.5-24.9)	14 17.5%	7 9.7%	21 13.8%
Overweight (25-29.9)	22 27.5%	22 30.6%	44 28.9%
Obese (≥30)	43 53.8%	42 58.3%	85 55.9%
Oxygen saturation (percentage of oxygen saturation) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [percentage of oxygen saturation]	97	97	97
Most severe COVID 19 symptom at baseline (Count of Participants)
Loss of sense of smell	26 32.5%	18 25%	44 28.9%
Fatigue	17 21.3%	18 25%	35 23%
Body aches	9 11.3%	13 18.1%	22 14.5%
Cough	9 11.3%	1 1.4%	10 6.6%
Subjective fever	8 10%	4 5.6%	12 7.9%
Loss of appetite	3 3.8%	8 11.1%	11 7.2%
Chills	3 3.8%	6 8.3%	9 5.9%
Shortness of breath	2 2.5%	1 1.4%	3 2%
Loss of taste	2 2.5%	2 2.8%	4 2.6%
Nausea	1 1.3%	1 1.4%	2 1.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Met Clinical Worsening
Description	Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.
Time Frame	RCT (approximately 15 days)

Outcome Measure Data

Analysis Population Description

The primary and secondary end points were measured using participants' self-reported responses on twice-daily surveys during the 15 days after randomization that were corroborated by research staff with phone contact.

Arm/Group Title	Fluvoxamine	Placebo
Arm/Group Description	Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days. Fluvoxamine: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.	Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days. Placebo: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.
Measure Participants	80	72
Count of Participants [Participants]	0 0%	6 8.3%

2. Secondary Outcome

Title	Clinical Deterioration on a Likert-type Scale (0-6)
Description	(0) none; (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.
Time Frame	RCT (approximately 15 days)

Outcome Measure Data

Analysis Population Description

The primary and secondary end points were measured using participants' self-reported responses on twice-daily surveys during the 15 days after randomization that were corroborated by research staff with phone contact.

Arm/Group Title	Fluvoxamine	Placebo
Arm/Group Description	Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days. Fluvoxamine: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.	Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days. Placebo: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.
Measure Participants	80	72
0 (none)	80 100%	66 91.7%
1, shortness of breath and oxygen saturation less than 92% but no supplemental oxygen needed	0 0%	2 2.8%
2, O2 saturation plus supplemental oxygen requirement	0 0%	0 0%
3, oxygen saturation less than 92% + supplemental O2 and hospitalized related to dyspnea or hypoxia	0 0%	3 4.2%
4, the above, plus ventilator support requirement;	0 0%	0 0%
5, oxygen < 92%, + supplemental O2, hospitalized related to dyspnea/hypoxia + ventilator 3 days	0 0%	1 1.4%
6, Death	0 0%	0 0%

Adverse Events

Time Frame	Adverse event data were collected daily via participant self-report during the 15 day RCT and again at the 30 day follow-up for both the fluvoxamine and placebo groups.
Arm/Group Title	Fluvoxamine		Placebo
Arm/Group Description	Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days. Fluvoxamine: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.		Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days. Placebo: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.
All Cause Mortality
	Fluvoxamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/72 (0%)
Serious Adverse Events
	Fluvoxamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/80 (1.3%)		6/72 (8.3%)
General disorders
Dehydration	1/80 (1.3%)	1	0/72 (0%)	0
Exacerbation of COVID 19 with hospitalization	0/80 (0%)	0	1/72 (1.4%)	1
Flank Pain (hospitalized)	0/80 (0%)	0	1/72 (1.4%)	1
Exacerbation of COVID 19 with hospitalization	0/80 (0%)	0	1/72 (1.4%)	1
Exacerbation of COVID 19 with hospitalization	0/80 (0%)	0	1/72 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute chronic respiratory failure with hypoxia and hypercapnia (hospitalized)	0/80 (0%)	0	1/72 (1.4%)	1
Bilateral multi-focal pneumonia with shortness of breath and low oxygen saturation (hospitalized)	0/80 (0%)	0	1/72 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Fluvoxamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/80 (16.3%)		28/72 (38.9%)
Blood and lymphatic system disorders
Hypercapnia	0/80 (0%)	0	1/72 (1.4%)	1
Gastrointestinal disorders
Headache or head pain	2/80 (2.5%)	2	1/72 (1.4%)	1
Gastroenteritis, nausea, or vomiting	1/80 (1.3%)	1	5/72 (6.9%)	5
General disorders
Bacterial infection	1/80 (1.3%)	1	0/72 (0%)	0
Vasovagal syncope	1/80 (1.3%)	1	0/72 (0%)	0
Teeth chattering	1/80 (1.3%)	1	0/72 (0%)	0
Dehydration	1/80 (1.3%)	1	0/72 (0%)	0
Fever	0/80 (0%)	0	1/72 (1.4%)	1
Flank pain	0/80 (0%)	0	1/72 (1.4%)	1
Musculoskeletal and connective tissue disorders
Muscle aches	1/80 (1.3%)	1	0/72 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/80 (3.8%)	3	6/72 (8.3%)	6
Shortness of breath	2/80 (2.5%)	2	4/72 (5.6%)	4
Low oxygen saturation or hypoxia	0/80 (0%)	0	6/72 (8.3%)	6
Chest pain or tightness	0/80 (0%)	0	2/72 (2.8%)	2
Acute respiratory failure	0/80 (0%)	0	1/72 (1.4%)	1

Limitations/Caveats

It was a small study and was conducted within a single geographic area; there was a small number of end point events; it is possible that the differences in clinical deterioration may have been a reflection of the comparative baseline distributions of O2 saturation rather than an effect of treatment; the method of measuring the most severe baseline symptom over time did not appear to provide valid data; the follow-up was short; the 7-point scale created for this study has not been validated.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.