ACTIV-5 /​ Big Effect Trial (BET-C) for the Treatment of COVID-19

Beigel et al., NCT04988035, ACTIV-5 BET-C, NCT04988035, Apr 2022
Mortality -43% improvement lower risk ← → higher risk Ventilation -17% Recovery -54% Improvement, 2 categ.. -37% Improvement, 1 categ.. -30% Hospitalization time -19% Danicopan  ACTIV-5 BET-C  LATE TREATMENT RCT Is late treatment with danicopan beneficial for COVID-19? Double-blind RCT 201 patients in the USA Worse recovery with danicopan (p=0.015) c19early.org Beigel et al., NCT04988035, April 2022 0 0.5 1 1.5 2+ RR
RCT 201 hospitalized COVID-19 patients showing increased risk with danicopan treatment, with statistical significance for time to sustained recovery.
Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments1. 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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risk of death, 42.6% higher, RR 1.43, p = 0.34, treatment 19 of 98 (19.4%), control 14 of 103 (13.6%).
risk of mechanical ventilation, 16.8% higher, RR 1.17, p = 0.69, treatment 16 of 91 (17.6%), control 14 of 93 (15.1%), mechanical ventilation or ECMO.
risk of no recovery, 53.8% higher, HR 1.54, p = 0.01, treatment 96, control 99, inverted to make HR<1 favor treatment, Cox proportional hazards.
risk of no improvement, 37.0% higher, HR 1.37, p = 0.06, treatment 96, control 99, inverted to make HR<1 favor treatment, 2 categories, Cox proportional hazards.
risk of no improvement, 29.9% higher, HR 1.30, p = 0.11, treatment 96, control 99, inverted to make HR<1 favor treatment, 1 category, Cox proportional hazards.
hospitalization time, 18.8% higher, relative time 1.19, p = 0.40, treatment median 9.5 IQR 19.0 n=96, control median 8.0 IQR 14.0 n=99.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Beigel et al., 23 Apr 2022, Double Blind Randomized Controlled Trial, placebo-controlled, USA, preprint, 1 author, trial NCT04988035 (history) (ACTIV-5 BET-C). Contact: jbeigel@niaid.nih.gov.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR 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 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda 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 Syria 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
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.
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