Covid-19 living Data

Fluvoxamine vs Placebo (RCT)

Mild outpatients

FOREST PLOTS -2022-03-04

Studies description

Trial NCT04342663
Publication Lenze E, JAMA (2020) (published paper)
Dates: 2020-04-10 to 2020-08-05
Funding: Mixed (Taylor Family Institute for Innovative Psychiatric Treatment at Washington University; COVID-19 Early Treat Fund; Center for Brain Research in Mood Disorders at Washington University; Bantly Foundation; National Inst)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : * / USA Follow-up duration (days): 45
Inclusion criteria	Adults living in the community with SARS-CoV-2 infection confirmed by polymerase chain reaction assay Symptomatic within 7 days of the first dose of study medication (fever, cough, myalgia, mild dyspnea, diarrhea, vomiting, anosmia, ageusia, sore throat)
Exclusion criteria	Having COVID-19 that required hospitalization or evidence of the primary end point with oxygen saturation less than 92% on room air at the time of randomization Severe underlying lung disease (eg, chronic obstructive pulmonary disease or required home oxygen, interstitial lung disease, pulmonary hypertension) Decompensated cirrhosis Congestive heart failure (New York Heart Association class III or IV) Immunocompromised (eg, solid organ transplant recipient or donor, bone marrow transplant recipient, AIDS, or taking immunosuppressant biologic drugs or highdose corticosteroids [>20mg/d of prednisone]
Interventions
	Treatment Fluvoxamine 50 mg orally on day 1, then 100 mg two times per day for 2 days, then 100 mg three times per day through day 15.
	Control Placebo
Participants
	Randomized participants : Fluvoxamine=92 Placebo=89
	Characteristics of participants N= 181 Mean age : NR 43 males Severity : Mild: n= 152/ Asymptomatic: n=0
Primary outcome
	In the register Time to clinical worsening [Time Frame: 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%
	In the report Clinical deterioration: (1) presence of dyspnea (ie, shortness of breath) or hospitalization for shortness of breath or pneumonia and (2) decrease in O2 saturation (<92%) on room air or supplemental O2 requirement to maintain O2 saturation of >= 92%
Documents avalaible	Protocol Yes. In English Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the trial registry, protocol and supplementary appendices were used in data extraction and assessment of risk of bias. The statistical analysis plan contained in the protocol was minimal. There were no substantive differences between the published article, the trial registry and the protocol in terms of population, procedures, treatments or outcomes. The trial employed a wholly remote, contactless design in which COVID-19 patients in the community were recruited, screened, and followed up daily either online or by telephone. Study materials (treatment or placebo, oxygen saturation monitor, an automated blood pressure monitor, and a thermometer) were delivered to the doorstep. The trial achieved its pre-specified sample size.

Trial NCT04727424
Publication TOGETHER - Reis G, Lancet Glob (2021) (published paper)
Dates: 2021-01-20 to 2021-08-05
Funding: Public/non profit (FastGrants; The Rainwater Foundation.)
Conflict of interest: No

Methods
	RCT Blinding: quadruple blinding
	Location : Multicenter / Brazil Follow-up duration (days): 28
Inclusion criteria	Patients older than 18 years Presenting to an outpatient care setting with an acute clinical condition consistent with COVID-19 and symptoms beginning within 7 days of the screening date, or positive rapid test for SARS-CoV-2 antigen done at the time of screening or patient with positive SARS-CoV-2 diagnostic test within 7 days of symptom onset At least one additional criterion for high risk: diabetes systemic arterial hypertension requiring at least one oral medication for treatment known cardiovascular disease (heart failure, congenital heart disease, valve disease, coronary artery disease, cardiomyopathies being treated, clinically manifested heart disease and with clinical repercussion) symptomatic lung disease or treatment for such (emphysema, fibrosing diseases) symptomatic asthma requiring chronic use of agents to control symptoms smoking obesity, defined as body-mass index greater than 30 kg/m² (weight and height information provided by the patient) having had a transplant stage IV chronic kidney disease or on dialysis immunosuppression or use of corticosteroid therapy (equivalent to at least 10 mg of prednisone per day) or immunosuppressive therapy history of cancer in the last 0·5 years or undergoing current cancer treatment or aged 50 years or older and unvaccinated status patients with negative test taken early and becoming positive a few days later were eligible, if they were less than 7 days after the onset of flu-like symptoms
Exclusion criteria	Diagnostic examination for SARS-CoV-2 negative associated with acute flu-like symptoms Acute respiratory condition compatible with COVID-19 treated in primary care and previously requiring hospitalisation Acute respiratory condition owing to other causes Received vaccination for SARS-CoV-2 Dyspnoea secondary to other acute and chronic respiratory causes or infections (eg, decompensated chronic obstructive pulmonary disease, acute bronchitis, pneumonia, primary pulmonary arterial hypertension) Current use of SSRIs (use of other serotonin reuptake inhibitors were not excluded) Uncontrolled psychiatric disorders or suicidal ideation inability or unwillingness to follow research guidelines and procedures Pregnant.
Interventions
	Treatment Fluvoxamine 100 mg orally twice a day for 10 days
	Control Placebo
Participants
	Randomized participants : Fluvoxamine=741 Placebo=756
	Characteristics of participants N= 1497 Mean age : NR 635 males Severity : Mild: n= 1497/ Asymptomatic: n=0
Primary outcome
	In the register 1. Rate of fluvoxamine, ivermectin, doxasozin, peginterferon Lambda and peginterferon beta in changing the need for emergency care AND observation for more than 06 hours due to the worsening of COVID-19; [ Time Frame: 28 days ] Evaluation of emergency visits and observation unit stay > 06 hours 2. Rate of fluvoxamine, ivermectin, doxasozin, peginterferon lambda and peginterferon beta in changing need for Hospitalization due to COVID-19 progression and related complications, including lower respiratory tract infection (LRTI) [ Time Frame: 28 days ] Hospitalization due to COVID-19 progression and related complications
	In the report Composite endpoint of medical admission to a hospital setting due to COVID-19- related illness defined as COVID-19 emergency setting visits with participants remaining under observation for more than 6 h or referral to further hospitalisation due to the progression of COVID-19 within 28 days of randomisation.
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the pre-print, the study registry, master protocol, supplementary appendix and statistical analysis plan were used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. The primary outcome indicated in registry reflects the primary outcome reported in the paper. A number of secondary outcomes in the registry (WHO ordinal scale, time in ICU, Health and Functioning after COVID-19 disease) were not reported in the published article. This study was updated on November 17th, 2021 with data from the published journal report.