Table 2.

Continued.

Trial	Intervention/clinical setting	Patient numbers (n)	Proposed mechanism of action	Primary and secondary outcome measures	Results
ACTIV-629	Ivermectin 400 μg/kg for three consecutive days vs Placebo Clinical setting: Community patients with mild-to-moderate COVID-19	Ivermectin—1591 Placebo—774	Antiviral	1—time to sustained recovery, defined as the third of three consecutive symptom free days 2°—hospitalization or death at day 28	• A hazard ratio (HR) of 1.07 was reported for improvement in time to recovery (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery in the ivermectin group was 12 days (IQR, 11-13) versus 13 days (IQR, 12-14) in the placebo group. Ten hospitalizations/ deaths were reported in the ivermectin group versus 9 events in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]) • Treatment did not lower incidence of hospitalization or death among outpatients with COVID-1929
ACTIV-630	Inhaled fluticasone furoate 200 μg once daily for 14 days vs Placebo Clinical setting: Community patients with mild-to-moderate COVID-19	Fluticasone furoate—656 Placebo—621	Anti-inflammatory	1—time to sustained recovery, defined as the third of three consecutive symptom free days. 2°—Hospitalization or death at day 28	• No improvement in time to recovery was observed with fluticasone compared with placebo (HR 1.01, 95% credible interval [CrI] 0.91–1.12; posterior probability for benefit [HR > 1] = 0.56). • A total of 24 participants (3.7%) in the fluticasone arm required urgent care or were hospitalized compared with 13 (2.1%) in the placebo arm (HR 1.9, 95% CrI 0.8–3.5; posterior probability for benefit [HR < 1] = 0.03).
PRINCIPLE31	Oral doxycycline (200 mg on day 1, then 100 mg once daily for the following 6 days) plus usual care vs Usual care plus other interventions vs Usual care alone	Doxycycline + usual care—780 Usual care plus other interventions—780 Usual care alone—948	Antiviral	1—time to first self-reported recovery and hospital admission or death related to COVID-19 at 28 days (co-primary endpoints)	• There was limited evidence of a difference in median time to first self-reported recovery between the usual care plus doxycycline group and the usual care only group (9·6 [95% Bayesian credible interval [BCI] 8·3 to 11·0] days vs 10·1 [8·7 to 11·7] days, HR 1·04 [95% BCI 0·93 to 1·17]). The estimated benefit in median time to first self-reported recovery was 0·5 days [95% BCI -0·99 to 2·04]. The probability of a clinically meaningful benefit (defined as ≥1·5 days) was 0·10. Hospitalization or death related to COVID-19 occurred in 41 (crude percentage 5·3%) participants in the usual care plus doxycycline group compared to 43 (4·5%) in the
PRINCIPLE32	Azithromycin 500 mg daily for 3 days vs Usual care plus other interventions vs Usual care alone	Azithromycin + usual care—540 Usual care + other interventions—850 Usual care alone—875	Antiviral	1—Time to first self-reported recovery and hospital admission or death related to COVID-19 at 28 days (co-primary endpoints)	• No clinically meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone was observed (HR 1·08, 95% BCI 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability of a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. A total of 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalized (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2).
PRINCIPLE33	Colchicine vs Usual care vs Usual care + other interventions	Colchicine—156 Usual care alone—1145 Usual care + other interventions—1454	Antiviral Anti-inflammatory	1—Time to first self-reported recovery and hospital admission or death related to COVID-19 at 28 days (co-primary endpoints)	• Time to first self-reported recovery was similar compared with usual care with an estimated HR of 0.919 [95% credible interval 0.72 to 1.16] and an estimated increase of 1.14 days [−1.86 to 5.21] in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was determined to be low at 1.8%. The rate of COVID-19 related hospitalizations/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 [0.28 to 1.89] and an estimated difference of −0.4% [−2.7% to 2.4].

Key: SC—subcutaneous.