Table 2.
Select randomized controlled trials of antivirals and immunomodulators for the therapy of COVID-19a
| Study | Study design | Population | Outcomes |
|---|---|---|---|
| Remdesivir (Veklury™) | |||
| PINETREE [24] | 3 days remdesivir vs. placebo |
• Mild/moderate symptoms • Outpatient • High risk for severe disease • Unvaccinated • ≤ 7 days of symptom onset |
• 28-day hospitalization and mortality: RRR 87% |
| ACTT-1 [16] | ≤ 10 days remdesivir vs. placebo |
• One of SpO2 < 94% on room air, need for supplemental oxygen, need for mechanical ventilation, respiratory rate ≥ 24 min−1 • Inpatient |
• Time to recovery: 10 days in remdesivir arm vs. 15 days in placebo arm (benefit highest in those receiving low-flow supplemental oxygen • No significant improvement in 28-day mortality |
| DisCoVeRy [17] | 5–10 days remdesivir vs. SOC |
• One of SpO2 < 94% on room air, need for supplemental oxygen, need for high-flow oxygen device, need non-invasive or mechanical ventilation • Inpatient • Any duration from symptom onset |
• No significant improvement in clinical status, mortality, or viral reduction for patients with > 7 days of symptoms and requiring supplemental oxygen or ventilatory support |
| WHO solidarity [18•] | 10 days remdesivir vs. SOC |
• Inpatient • No prior COVID therapy |
• No significant reduction in in-hospital mortality overall, though slight benefit (RRR 13%) in those on oxygen but not mechanically ventilated |
| Nirmatrelvir/ritonavir (Paxlovid™) | |||
| EPIC-HR [26] | 5 days nirmatrelvir/ritonavir vs. placebo |
• Mild/moderate symptoms • Outpatient • High risk for severe disease • Unvaccinated • ≤ 5 days of symptom onset |
• 28-day hospitalization and mortality: RRR 89% |
| Molnupiravir (Lagevrio™) | |||
| MOVe-OUT [30] | 5 days molnupiravir vs. placebo |
• Mild/moderate symptoms • Outpatient • High risk for severe disease • Unvaccinated • ≤ 5 days of symptom onset |
• 28-day hospitalization and mortality: RRR 30% |
| Corticosteroids | |||
| RECOVERY [51] | 10 days dexamethasone and SOC vs. SOC alone | • Inpatient |
• No significant reduction in 28-mortality in patients not requiring supplemental oxygen • 28-mortality: RRR 17–36% in those requiring supplemental oxygen, mechanical ventilation or ECMO |
| STEROID 2 [55] | In addition to SOC, 10 days of dexamethasone 12 mg daily vs. 10 days of dexamethasone 6 mg daily |
• Inpatient • Requiring > = 10 L/min supplemental oxygen, non-invasive ventilation or mechanical ventilation |
• No significant difference in life support-free days, 28-mortality, or 90-day mortality |
| Janus kinase inhibitors | |||
| ACTT-2 [57] | ≤ 10 days remdesivir and ≤ 14 days baricitinib vs. ≤ 10 days remdesivir and placebo |
• One of: pulmonary infiltrates, SpO2 < 94% on room air, need for supplemental oxygen, need for high-flow oxygen device, need non-invasive or mechanical ventilation • Inpatient, ≤ 3 days from admission • Excluded patients receiving glucocorticoids for COVID-19 |
• Time to recovery: 7 days in baricitinib arm vs. 8 days in placebo arm. This benefit was higher in those receiving high-flow nasal cannulae or non-invasive ventilation (10 vs. 18 days) |
| COV-BARRIER [58] | In addition to SOC, ≤ 14 days baricitinib vs. placebo |
• Pneumonia on imaging or symptomatic infection • Inpatient • Elevated CRP, D-dimer, lactate dehydrogenase, or ferritin • Excluded patients on mechanical ventilation or ECMO |
• No significant difference in composite endpoint of 28-day mortality, need for high-flow oxygen device, need non-invasive or mechanical ventilation, or ECMO • 28-day mortality: RRR 43% (69% in those on supplemental oxygen but not steroids) |
| STOP-COVID [59] | ≤ 14 days tofacitinib vs. placebo |
• Pneumonia on imaging • Inpatient, ≤ 3 days from admission • Excluded patients on non-invasive or mechanical ventilation or ECMO |
• 28-day mortality or respiratory failure: RRR 37% |
| Interleukin-6 receptor inhibitors | |||
| REMAP-CAP [64] | In addition to SOC, 1 dose of tocilizumab vs. 1 dose of sarilumab vs. no immunomodulation |
• Admitted to ICU • ≤ 24 h from starting one of: supplemental oxygen via high-flow nasal cannulae, non-invasive or mechanical ventilation, vasopressor support |
• 21-day composite score of in-hospital mortality and organ support free days: aOR 1.87 (tocilizumab), aOR 1.85 (sarilumab) • 90-day mortality: RRR 38% (combined tocilizumab and sarilumab vs. control) |
| RECOVERY [63] | 1 dose tocilizumab and SOC vs. SOC alone |
• One of: oxygen saturation < 92% on room air, need for supplemental oxygen, CRP > 75 mg/L • Inpatient |
• 28-day mortality: RRR 15% • Invasive mechanical ventilation: RRR 21% • Length of hospital stay > 28 days: RRR 18% |
CRP C-reactive protein, RCT randomized control trial, RRR relative risk reduction, SOC standard of care, SpO2 oxygen saturation
aDetails of all relevant clinical studies are available elsewhere [93]