Presentation noting that STOP COVID 2 was terminated early for futility with only 30/551 cases of detioration and no significant treatment effect. The main results are not available yet, however partial results presented suggest that early treatment was more effective. Hospitalization results are from [medrxiv.org].
Abstract: Fluvoxamine for early treatment of COVID-19:
the STOP COVID trials
Eric Lenze, M.D.
Wallace & Lucille Renard Professor of Psychiatry & Anesthesiology
Washington University School of Medicine, St Louis, MO
Lenze disclosures (past 36 months)
• Grant support (non-federal): COVID Early Treatment Fund,
Mercatus Center Emergent Ventures (Fast Grants), the Skoll
Foundation, the Taylor Family Institute for Innovative
Psychiatric Research, the Center for Brain Research in Mood
Disorders, the Patient-Centered Outcomes Research Institute,
Janssen, and the Barnes Jewish Foundation.
• Consulting fees: Janssen, Jazz Pharmaceuticals.
• Patent: Lenze & Reiersen have applied for a patent for the use
of fluvoxamine in the treatment of COVID-19.
Anatomy of innovations
Pearl Kendrick & Grace Eldering
Serendipity + trial & error
A collective enterprise
Rewind…March 25, 2020
To: Eric Lenze
From: Angela Reiersen
“…regarding the possibility of using SSRIs as potential treatment
for COVID-19 cytokine storm…especially fluvoxamine”
Angela Reiersen, M.D.
(Washington University, St Louis)
Observation of patients with
(Rare genetic disorder with
dysregulated Endoplasmic Reticulum
(ER) Stress Response)
Poor outcomes with sertraline;
better with other SSRIs
Review of pharmacology:
Many SSRIs also affect another
receptor, the Sigma-1 receptor (S1R) :
Many are S1R agonists (activators);
sertraline is S1R antagonist.
Review of S1R literature:
What do we know about the S1R and
ER stress response?
Dorian Rosen and Alban Gaultier
(at University of Virginia)
Fluvoxamine prevents death in mice
exposed to inflammatory triggers (such as
Fecal Induced Peritonitis [FIP])…
…and reduces cytokine production in human
blood exposed to Lipopolysaccharide (LPS,
another inflammatory trigger)
Rosen…& Gaultier, “Modification of the sigma-1 receptor-IRE1 pathway is beneficial in
preclinical models of inflammation and sepsis.” Science Translational Medicine, 2019
Hypothesis: Fluvoxamine activates S1R and
reduces IRE1-mediated inflammation
• The S1R modulates the ER stress
response, involved with virus-host
interactions and cytokine
• S1R agonist dampens inflammation
and interferes with viral functions
through inhibition of IRE1.
From Sukhatme, Reiersen, et al, “Fluvoxamine: A review of its mechanism of
action and its role in COVID-19”, Front Pharmacol 2021
S1R=sigma-1 receptor; ER=endoplasmic reticulum; IRE1=inositol-requiring 1 enzyme
STOP COVID trial
hypothesis: fluvoxamine, given early in
COVID-19, prevents clinical deterioration
Caline Mattar. M.D.
Fluvoxamine x 15d
Placebo x 15d
hospitalization + O2
Participants surveyed twice daily x 15 days
Reminder to take study medication
1st decision: start fast and be pragmatic
Use EHR to screen for SARS-CoV-2
PCR+ persons, then e-consent
Provide study supples (pills, pulse ox, BP cuff)
take the study
to the patient
3rd decision: non-contact but high-touch
Patients self-monitor and enter their data.
We call them to check on their status.
Many COVID trials failed. How we succeeded…
1st patient randomized
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.