Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial

Wannigama et al., eClinicalMedicine, 10.1016/j.eclinm.2024.102517, NCT05087381, Mar 2024
Ventilation, day 28 98% improvement lower risk ← → higher risk Ventilation, day 14 98% Ventilation, day 9 97% Oxygen therapy, day 28 100% Oxygen therapy, day 14 100% Oxygen therapy, day 9 100% Hospitalization, day 28 98% Hospitalization, day 14 98% Hospitalization, day 9 97% Long COVID 55% Bromhexine  Wannigama et al.  EARLY TREATMENT RCT Is early treatment with bromhexine + fluvoxamine/niclosamide beneficial? RCT 995 patients in Thailand (October 2021 - June 2022) Lower ventilation (p<0.0001) and lower oxygen therapy (p<0.0001) c19early.org Wannigama et al., eClinicalMedicine, 1.., Mar 2024 0 0.5 1 1.5 2+ RR
RCT 995 outpatients showing significantly lower progression with early treatment within 48 hours using fluvoxamine, fluvoxamine+bromhexine, fluvoxamine+cyproheptadine, and niclosamide+bromhexine.
70% of patients received treatment within 12 hours of symptom onset.
Treatments groups showed significantly lower long COVID (PASC). The combined treatment groups showed significantly lower viral load as early as day 3. The 3 combination arms were superior to fluvoxamine alone.
The study was open-label. 593 out of 1,900 randomized participants did not receive the treatment, mostly due to inability to confirm eligibility, however baseline characteristics were similar for these patients.
There was a very high hospitalization rate in the control arm. Authors note that the majority of cases were mild - the threshold for hospitalization may have been very low (in some places/times all cases were hospitalized). Authors also note that the patients requiring high flow oxygen all had the delta/alpha variants, and that the population has many health disparities.
Publication was over 500 days after the 90 day followup.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants1,2.
Important missing comments or errors? Let us know.
Study covers niclosamide, TMPRSS2 inhibitors, bromhexine, and fluvoxamine.
risk of mechanical ventilation, 98.5% lower, RR 0.02, p < 0.001, treatment 0 of 350 (0.0%), control 32 of 336 (9.5%), NNT 10, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 28.
risk of mechanical ventilation, 98.2% lower, RR 0.02, p < 0.001, treatment 0 of 350 (0.0%), control 27 of 336 (8.0%), NNT 12, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 14.
risk of mechanical ventilation, 97.5% lower, RR 0.03, p < 0.001, treatment 0 of 350 (0.0%), control 19 of 336 (5.7%), NNT 18, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 9.
risk of oxygen therapy, 99.7% lower, RR 0.003, p < 0.001, treatment 0 of 350 (0.0%), control 171 of 336 (50.9%), NNT 2.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 28.
risk of oxygen therapy, 99.7% lower, RR 0.003, p < 0.001, treatment 0 of 350 (0.0%), control 150 of 336 (44.6%), NNT 2.2, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 14.
risk of oxygen therapy, 99.6% lower, RR 0.004, p < 0.001, treatment 0 of 350 (0.0%), control 117 of 336 (34.8%), NNT 2.9, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 9.
risk of hospitalization, 98.5% lower, RR 0.02, p < 0.001, treatment 0 of 350 (0.0%), control 32 of 336 (9.5%), NNT 10, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 28.
risk of hospitalization, 98.2% lower, RR 0.02, p < 0.001, treatment 0 of 350 (0.0%), control 27 of 336 (8.0%), NNT 12, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 14.
risk of hospitalization, 97.5% lower, RR 0.03, p < 0.001, treatment 0 of 350 (0.0%), control 19 of 336 (5.7%), NNT 18, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), combined bromhexine arms, day 9.
risk of long COVID, 55.1% lower, RR 0.45, p < 0.001, treatment 157 of 350 (44.9%), control 336 of 336 (100.0%), NNT 1.8, combined bromhexine arms, day 90.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wannigama et al., 14 Mar 2024, Randomized Controlled Trial, Thailand, peer-reviewed, 29 authors, study period 1 October, 2021 - 21 June, 2022, average treatment delay 0.5 days, this trial uses multiple treatments in the treatment arm (combined with fluvoxamine/niclosamide) - results of individual treatments may vary, trial NCT05087381 (history). Contact: Dhammika.L@chula.ac.th, Phatthranit.pha@mahidol.edu, gochi.akk@gmail.com.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org December 2025 Thailand United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Sri Lanka Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Chad Syria Thailand favored low-cost treatments.The average efficacy of treatments was high.Low-cost treatments improve early treatment, andprovide 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 December 2025 Thailand United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia CAR Chad Syria Thailand favored low-cost treatments.The average efficacy was high.Low-cost protocols improve early treatment,and add complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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. IMA and WCH provide treatment protocols.
  or use drag and drop   
Submit    
Post
Share
@CovidAnalysis
FAQ
Public domain CC0 1.0