News Report · Infectious Disease

REVIVE: Fluvoxamine Reduces Fatigue Severity (−0.43 FSS) vs Placebo

July 20, 2026

Participants

399

Primary outcome

Change in Fatigue Severity Scale (FSS) score

Fluvoxamine vs placebo (day 60)

Mean difference −0.43 (95% CrI, −0.80 to −0.07)

Fluvoxamine vs placebo (day 90)

Mean difference −0.58 (95% CrI, −0.98 to −0.16)

Adverse-event rates

Fluvoxamine 20.0%; Metformin 28.8%; Placebo 29.7%

ClinicalTrials.gov ID

NCT06128967

Funding

The Latona Foundation

Clinical Perspective

Primary care clinicians and infectious disease clinicians managing outpatients with long COVID fatigue may consider these trial results when discussing therapeutic options, as the REVIVE trial provides randomized data that fluvoxamine produced modest reductions in FSS scores compared with placebo ^[1]. The trial data support that fluvoxamine—but not metformin—was associated with lower reported adverse-event frequency in this cohort ^[1]. How durable the effect beyond 90 days is and whether benefits extend to other long COVID symptoms remain unanswered questions?

Dr. Simran Kohli · Infectious Diseases

The adaptive randomized REVIVE trial found that fluvoxamine reduced fatigue severity compared with placebo in adults with persistent fatigue 90 or more days after confirmed SARS-CoV-2 infection, with a mean difference in Fatigue Severity Scale (FSS) score of −0.43 at day 60 (95% CrI, −0.80 to −0.07) and a sustained effect at day 90 (mean difference, −0.58; 95% CrI, −0.98 to −0.16) ^[1]. The trial enrolled 399 adults and also tested metformin, which showed no significant benefit versus placebo ^[1].

Clinical Context

Postacute sequelae of SARS-CoV-2 infection (PASC), commonly called long COVID, includes fatigue as a prevalent and debilitating symptom, and effective outpatient therapeutic strategies remain limited ^[1]. The REVIVE investigators tested two repurposed oral agents—fluvoxamine and metformin—targeting fatigue specifically, acknowledging fatigue as the trial’s primary focus and noting that other long COVID symptoms were not addressed by the primary outcome ^[1]. The trial was conducted at outpatient sites in Brazil and was designed as an adaptive, randomized, placebo-controlled study to evaluate change in Fatigue Severity Scale score as the primary efficacy endpoint ^[1]. Funding for the trial was provided by The Latona Foundation ^[1].

Key Findings

The REVIVE adaptive randomized trial showed fluvoxamine reduced the Fatigue Severity Scale (FSS) score by 0.43 versus placebo at day 60 (mean difference, −0.43; 95% CrI, −0.80 to −0.07) ^[1].
The fluvoxamine effect was sustained at day 90 with a mean difference in FSS score of −0.58 versus placebo (95% CrI, −0.98 to −0.16) ^[1].
Metformin did not show a benefit on the primary outcome of FSS change in this trial ^[1].
Trial dosing (as reported): fluvoxamine 100 mg twice daily and metformin 750 mg twice daily, each given for 60 days, versus matching placebo ^[1].
Clinicians should consult current prescribing information for full dosing guidance.
Adverse-event rates reported were 20.0% with fluvoxamine, 28.8% with metformin, and 29.7% with placebo; grade 3 and higher adverse events were rare across groups ^[1].

Safety & Tolerability

Adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%) ^[1].
Grade 3 and higher adverse events were rare across all groups in the trial ^[1].

Study Design

REVIVE was a randomized, placebo-controlled, adaptive outpatient trial enrolling 399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection ^[1]. Participants were randomly assigned to fluvoxamine 100 mg twice daily, metformin 750 mg twice daily, or matching placebo for 60 days; the primary outcome was change in Fatigue Severity Scale (FSS) score ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The trial included follow-up to day 90 for sustained effects and was conducted at outpatient sites in Brazil; the ClinicalTrials.gov identifier is NCT06128967 ^[1]. The primary funding source was The Latona Foundation ^[1]. The investigators noted that the 90-day follow-up limits conclusions about durability and that focusing on fatigue as the primary outcome does not address other long COVID symptoms ^[1].

FAQ

Q1 What did the REVIVE trial show?

The REVIVE trial randomized 399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection to fluvoxamine, metformin, or placebo and measured change in Fatigue Severity Scale (FSS) score. Fluvoxamine reduced FSS score versus placebo at day 60 with a mean difference of −0.43 (95% CrI, −0.80 to −0.07) and showed a sustained effect at day 90 (mean difference, −0.58; 95% CrI, −0.98 to −0.16). Metformin did not show benefit on the primary outcome. Adverse-event rates were 20.0% with fluvoxamine, 28.8% with metformin, and 29.7% with placebo.

Q2 Who was enrolled in the REVIVE trial?

The trial enrolled 399 adult outpatients at sites in Brazil who had fatigue persisting for 90 or more days after a confirmed SARS-CoV-2 infection. Participants were randomized to receive fluvoxamine, metformin, or matching placebo, and the primary outcome was change in Fatigue Severity Scale score measured at day 60 with follow-up at day 90.

Q3 What were the side effects in the REVIVE trial?

Reported adverse-event frequencies were 20.0% in the fluvoxamine group, 28.8% in the metformin group, and 29.7% in the placebo group. The investigators reported that grade 3 and higher adverse events were rare across all treatment groups. The trial report did not provide a detailed breakdown of specific adverse-event types in the provided excerpts.

Q4 What does the REVIVE trial mean for clinical practice?

REVIVE provides randomized evidence that fluvoxamine reduced fatigue severity versus placebo at day 60 with sustained effect at day 90 in adults with long COVID–related fatigue, while metformin did not show benefit. Clinicians weighing off-label or repurposed options can reference these trial results and the reported adverse-event rates when discussing therapy, but questions remain about durability beyond 90 days and effects on other long COVID symptoms.

References

PubMed — Primary trial publication (PMID 41911553)

REVIVE: Fluvoxamine Reduces Fatigue Severity (−0.43 FSS) vs Placebo

REVIVE: Fluvoxamine Reduces Fatigue Severity (−0.43 FSS) vs Placebo

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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