c19early.org COVID-19 treatment researchCOVID-19 treatments

A 2-Part, 2-Arm, Phase 2, Randomized, Double-Blind, Placebo-Controlled Study on the Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection

First Wave BioPharma, NCT04858425, RESERVOIR, NCT04858425, May 2023
Late treatmentDouble-blind RCT · NCT04858425 · 118 patients · USA
Niclosamide for COVID-19
RESERVOIR First Wave BioPharma NCT04858425 · May 2023
Trial underpowered to detect differences

Niclosamide for COVID-19

56th treatment shown to reduce risk in August 2025, now with p = 0.0069 from 7 studies.
Lower risk for recovery.

No treatment is 100% effective.
Protocols combine treatments.

6,700+ studies · 220+ treatments

c19early.org
Meta-analysis
RCT 118 hospitalized patients with gastrointestinal infection showing no significant difference in viral clearance with niclosamide. Viral clearance results are available on clinicaltrials.gov but clinical results are missing.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter et al. show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments2. Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
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OutcomeImprovementEffect · pTreatmentControl
risk of no viral clearance 22.7% lower · RR 0.77 · p = 0.61 22.7% lowerRR 0.77p = 0.61 8 of 60 (13.3%) 10 of 58 (17.2%) treatment 8 of 60 (13.3%), control 10 of 58 (17.2%)NNT 26day 43
risk of no viral clearance 33.1% lower · RR 0.67 · p = 0.35 33.1% lowerRR 0.67p = 0.35 9 of 60 (15.0%) 13 of 58 (22.4%) treatment 9 of 60 (15.0%), control 13 of 58 (22.4%)NNT 13day 36
risk of no viral clearance 42.0% lower · RR 0.58 · p = 0.17 42.0% lowerRR 0.58p = 0.17 9 of 60 (15.0%) 15 of 58 (25.9%) treatment 9 of 60 (15.0%), control 15 of 58 (25.9%)NNT 9.2day 29
risk of no viral clearance 27.5% lower · RR 0.73 · p = 0.39 27.5% lowerRR 0.73p = 0.39 12 of 60 (20.0%) 16 of 58 (27.6%) treatment 12 of 60 (20.0%), control 16 of 58 (27.6%)NNT 13day 22
risk of no viral clearance 22.7% lower · RR 0.77 · p = 0.34 22.7% lowerRR 0.77p = 0.34 20 of 60 (33.3%) 25 of 58 (43.1%) treatment 20 of 60 (33.3%), control 25 of 58 (43.1%)NNT 10day 15
risk of no viral clearance 0.8% lower · RR 0.99 · p = 1.00 0.8% lowerRR 0.99p = 1.00 39 of 60 (65.0%) 38 of 58 (65.5%) treatment 39 of 60 (65.0%), control 38 of 58 (65.5%)NNT 193day 8
risk of no viral clearance 2.6% higher · RR 1.03 · p = 0.80 2.6% higherRR 1.03p = 0.80 52 of 60 (86.7%) 49 of 58 (84.5%) treatment 52 of 60 (86.7%), control 49 of 58 (84.5%)day 4

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First Wave BioPharma et al., 1 May 2023, Double Blind Randomized Controlled Trial, placebo-controlled, USA, preprint, 1 author, trial NCT04858425 (history) (RESERVOIR).
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2026 USA Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Argentina Nepal Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea United Kingdom Saudi Arabia Algeria Morocco Yemen Poland Uzbekistan India China Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Taiwan Fiji Zambia Bosnia-Herzegovina Jordan Georgia Switzerland Dominican Republic Bolivia Côte d'Ivoire Eritrea Togo Bulgaria Greece Slovakia Iceland New Zealand Trinidad and Tobago Mongolia Czechia Belarus Israel Haiti North Macedonia Hong Kong Qatar Panama Serbia USA favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2026 USA Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Argentina Nepal Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea United Kingdom Saudi Arabia Algeria Morocco Yemen Poland Uzbekistan India China Venezuela DR Congo Madagascar Thailand Uganda Egypt Taiwan Fiji Zambia Jordan Georgia Switzerland Dominican Rep. Bolivia Côte d'Ivoire Eritrea Togo Sri Lanka Bulgaria Greece Slovakia New Zealand Trinidad and Tobago Mongolia Czechia Belarus Israel North Macedonia Hong Kong Qatar Panama Serbia USA favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Late treatment
is less effective