- Laboratory-confirmed SARS-CoV-2 infection
- ≥1 of the following criteria:
- Pulmonary infiltrates
- SpO2 ≤94% on room air
- Need for supplemental oxygen, high-flow oxygen, NIV, MV, or ECMO
Key Exclusion Criteria:
- ALT or AST >5 times ULN
- eGFR <30 mL/min
- Pregnancy or breastfeeding
Interventions:
- RDV 200 mg IV on Day 1, then RDV 100 mg daily for up to 9 more days (n = 541)
- Placebo for up to 10 days (n = 521)
Primary Endpoint:
- Time to clinical recovery
Key Secondary Endpoints
- Clinical status at Day 15, as measured by an OS
- Mortality by Day 29
- Occurrence of SAEs
Participant Characteristics:
- Mean age 58.9 years
- 53.3% White, 21.3% Black, 12.7% Asian, 23.5% Hispanic/Latinx
- 26.2% with 1 and 55.2% with ≥2 coexisting conditions
- 13.0% not on oxygen; 41.0% on supplemental oxygen; 18.2% on high-flow oxygen or NIV; 26.8% on MV or ECMO
- Median time from symptom onset to randomization was 9 days (IQR 6–12 days)
- 21.6% in RDV arm and 24.4% in placebo arm received corticosteroids during the study
Primary Outcomes:
- RDV reduced time to recovery compared to placebo (10 days vs. 15 days; rate ratio for recovery 1.29; 95% CI, 1.12–1.49; P < 0.001).
- Benefit of RDV was greatest in patients randomized during first 10 days after symptom onset and those who required supplemental oxygenation at enrollment.
- No difference in time to recovery for patients on high-flow oxygen, NIV, MV, or ECMO at enrollment.
Secondary Outcomes:
- Patients in RDV arm were more likely to show clinical improvement at Day 15 (OR 1.5; 95% CI, 1.2–1.9; P < 0.001).
- No difference between arms in mortality by Day 29.
- Proportion of patients with SAEs was similar between arms (25% vs. 32%).
- Wide range of disease severity among patients, and study was not powered to detect differences within subgroups
- Powered to detect differences in clinical improvement, not mortality
- No data on longer-term morbidity
Interpretation:
- In patients with severe COVID-19, RDV reduced time to clinical recovery.
- The benefit was most apparent in hospitalized patients who were receiving supplemental oxygen.
- There was no observed benefit in those on high-flow oxygen, NIV, MV, or ECMO, but study was not powered to detect differences within subgroups.
- Laboratory-confirmed SARS-CoV-2 infection
- Illness of any duration
- SpO2 ≤94% on room air or use of supplemental oxygen, high-flow oxygen devices, NIV, or MV
Key Exclusion Criteria:
- ALT or AST >5 times ULN
- Severe chronic kidney disease
Interventions:
- RDV 200 mg IV on Day 1, then RDV 100 mg IV once daily for up to 9 days (n = 429)
- SOC (n = 428)
Primary Endpoint:
- Clinical status at Day 15, as measured by an OS
Key Secondary Endpoint:
- Mortality at Day 29
- Occurrence of SAEs
Participant Characteristics:
- Median age 64 years; 70% men; 69% White
- 74% with ≥1 coexisting condition
- 40% received corticosteroids during the study
- Median days from symptom onset to randomization was 9 days in both arms
- 61% with moderate disease and 39% with severe disease
Primary Outcomes:
- No difference between arms in clinical status at Day 15 (OR 0.98; 95% CI, 0.77–1.25; P = 0.85).
- A prespecified subgroup analysis based on duration of symptoms found no significant difference in clinical status between arms.
Secondary Outcomes:
- No difference in mortality between arms (8% in RDV arm vs. 9% in SOC arm).
- No difference in the proportion of patients with SAEs between arms (33% in RDV arm vs. 31% in SOC arm; P = 0.48).
- Open-label study
- 440 participants in this study also enrolled in the Solidarity trial
Interpretation:
- There was no clinical benefit of RDV in hospitalized patients who were symptomatic for >7 days and who required supplemental oxygen.
- Aged ≥18 years
- Not known to have received any study drug
- Not expected to be transferred elsewhere within 72 hours
Interventions:
- RDV 200 mg IV on Day 0, then RDV 100 mg daily on Days 1–9 (n = 2,743)
- Local SOC (n = 2,708)
Primary Endpoint:
Key Secondary Endpoint:
Participant Characteristics:
- 47% aged 50–69 years; 18% aged ≥70 years
- 67% on supplemental oxygen and 9% on MV at entry
- Rates of comorbidities were similar between arms
- 48% in both arms received corticosteroids during the study
Primary:
- In-hospital mortality: 11.0% in RDV arm vs. 11.2% in SOC arm (rate ratio 0.95; 95% CI, 0.81–1.11)
Secondary Outcome:
- Initiation of MV: 10.8% in RDV arm vs. 10.5% in SOC arm
- Open-label design limits ability to assess time to recovery as RDV may have been continued even if patient improved
- No data on time from symptom onset to enrollment
- No assessment of outcomes post hospital discharge
Interpretation:
- RDV did not decrease in-hospital mortality or the need for MV compared to SOC.
- Laboratory-confirmed SARS-CoV-2 infection
- Pulmonary infiltrates
- SpO2 >94% on room air
Key Exclusion Criteria:
- ALT or AST >5 times ULN
- CrCl <50 mL/min
Interventions:
- RDV 200 mg IV on Day 1, then RDV 100 mg daily for 9 days (n = 193)
- RDV 200 mg IV on Day 1, then RDV 100 mg daily for 4 days (n = 191)
- Local SOC (n = 200)
Primary Endpoint:
- Clinical status at Day 11, as measured by an OS
Participant Characteristics:
- Demographic and baseline disease characteristics similar across arms
- Ranges for participant characteristics across the 3 arms:
- Median age 56–58 years
- Men: 60% to 63%
- 81% to 87% required no supplemental oxygen; 12% to 18% required low-flow oxygen; 1% required high-flow oxygen or NIV
- Concomitant medication use in the 10-day RDV, 5-day RDV, and SOC arms:
- Steroids: 15%, 17%, 19%
- Tocilizumab: 1%, 1%, 5%
- HCQ/CQ: 11%, 8%, 45%
- LPV/RTV: 6%, 5%, 22%
- AZM: 21%, 18%, 31%
- Median length of therapy was 6 days in 10-day RDV arm and 5 days in 5-day RDV arm
Primary Outcomes:
- 5-day RDV arm had significantly better clinical status at Day 11 than SOC arm (OR 1.65; 95% CI, 1.09–2.48; P = 0.02).
- No difference in clinical status at Day 11 between 10-day RDV arm and SOC arm (P = 0.18).
- Open-label design may have affected decisions on concomitant medications (e.g., more patients in the SOC arm received AZM, HCQ or CQ, and LPV/RTV) and time of hospital discharge
- No data on time to return to activity for discharged patients
Interpretation:
- Hospitalized patients with moderate COVID-19 who received 5 days of RDV had better clinical status at Day 11 than those who received SOC.
- There was no difference in the clinical status at Day 11 between patients who received 10 days of RDV and those who received SOC.
- Laboratory-confirmed COVID-19
- Pulmonary infiltrates and SpO2 ≤94% on room air or receipt of supplemental oxygen
Key Exclusion Criteria:
- Need for MV or ECMO
- Multiorgan failure
- ALT or AST >5 times ULN
- Estimated CrCl <50 mL/min
Interventions:
- RDV 200 mg IV on Day 1, then RDV 100 mg daily for 4 days (n = 200)
- RDV 200 mg IV on Day 1, then RDV 100 mg daily for 9 days (n = 197)
Primary Endpoint:
- Clinical status at Day 14, as measured by an OS
Key Secondary Endpoint:
- Time to clinical improvement
- Time to recovery
Participant Characteristics:
- Median age 61 years in 5-day arm vs. 62 years in 10-day arm
- 60% were men in 5-day arm vs. 68% in 10-day arm
- Oxygen requirements at baseline for the 5-day and 10-day arms:
- None: 17%, 11%
- Low-flow supplemental oxygen: 56%, 54%
- High-flow oxygen or NIV: 24%, 30%
- MV or ECMO: 2%, 5%
- Patients in 10-day arm had worse baseline clinical status than those in 5-day arm (P = 0.02)
Primary Outcome:
- After adjusting for baseline clinical status, Day 14 distribution in clinical status was similar between arms (P = 0.14).
Secondary Outcomes:
- Time to clinical improvement was similar between arms (10 days in 5-day arm vs. 11 days in 10-day arm).
- Median duration of hospitalization for patients who were discharged on or before Day 14 was similar between arms (7 days in 5-day arm vs. 8 days in 10-day arm).
- Open-label trial
- Baseline imbalances in clinical status of patients in 5-day and 10-day arms
Interpretation:
- In hospitalized patients with severe COVID-19 who were not receiving MV or ECMO, using RDV for 5 or 10 days had similar clinical benefits.
