Table 2a. Remdesivir: Selected Clinical Data

Last Updated: December 16, 2021

The clinical trials described in this table do not represent all the trials that the Panel reviewed while developing the recommendations for RDV. The studies summarized below are the randomized controlled trials that have had the greatest impact on the Panel’s recommendations.

Table 2a. Remdesivir: Selected Clinical Data
Methods	Results	Limitations and Interpretation
ACTT-1: Multinational, Placebo-Controlled, Double-Blind RCT of Remdesivir in Hospitalized Patients With COVID-19¹
Key Inclusion Criteria: 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%).	Key Limitations: 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.
DisCoVeRy: Open-Label, Adaptive RCT of Remdesivir in Hospitalized Patients With Moderate or Severe COVID-19 in Europe²
Key Inclusion Criteria: 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).	Key Limitations: 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.
WHO Solidarity Trial: Multinational, Open-Label, Adaptive RCT of Repurposed Drugs in Hospitalized Patients With COVID-19³
Key Inclusion Criteria: 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: In-hospital mortality Key Secondary Endpoint: Initiation of MV	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	Key Limitations: 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.
GS-US-540-5774 Study: Multinational, Open-Label RCT of 10 Days or 5 Days of Remdesivir Compared With Standard of Care in Hospitalized Patients With Moderate COVID-19⁴
Key Inclusion Criteria: 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).	Key Limitations: 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.
GS-US-540-5773 Study: Multinational, Open-Label RCT of 10 Days or 5 Days of Remdesivir Compared with Standard of Care in Hospitalized Patients With Moderate COVID-19⁵
Key Inclusion Criteria: 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).	Key Limitations: 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.
Key: ALT = alanine transaminase; AST = aspartate aminotransferase; AZM = azithromycin; CQ = chloroquine; CrCl = creatinine clearance; ECMO = extracorporeal membrane oxygenation; eGFR = estimated glomerular filtration rate; HCQ = hydroxychloroquine; IV = intravenous; LPV/RTV = lopinavir/ritonavir; MV = mechanical ventilation; NIV = noninvasive ventilation; OS = ordinal scale; the Panel = the COVID-19 Treatment Guidelines Panel; RCT = randomized controlled trial; RDV = remdesivir; SAE = serious adverse event; SOC = standard of care; SpO₂ = oxygen saturation; ULN = upper limit of normal

References

Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19—final report. N Engl J Med. 2020;383(19):1813-1826. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32445440.
Ader F, Bouscambert-Duchamp M, Hites M, et al. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a Phase 3, randomised, controlled, open-label trial. Lancet Infect Dis. 2021; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34534511.
WHO Solidarity Trial Consortium, Pan H, Peto R, et al. Repurposed antiviral drugs for COVID-19—interim WHO Solidarity Trial results. N Engl J Med. 2021;384(6):497-511. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33264556.
Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA. 2020;324(11):1048-1057. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32821939.
Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med. 2020;383(19):1827-1837. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32459919.