Table 4a. Remdesivir: Selected Clinical Data

Last Updated: August 8, 2022

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 those that have had the greatest impact on the Panel’s recommendations. Studies of hospitalized patients are listed first, followed by 1 study of nonhospitalized patients.

Table 4a. Remdesivir: Selected Clinical Data
Methods	Results	Limitations and Interpretation
ACTT-1: Multinational, Double-Blind, Placebo-Controlled Trial of Remdesivir in Hospitalized Patients With COVID-19 in 10 Countries¹
Key Inclusion Criteria Laboratory-confirmed SARS-CoV-2 infection ≥1 of the following: Pulmonary infiltrates SpO₂ ≤94% on room air Need for supplemental oxygen, HFNC oxygen, NIV, MV, or ECMO Key Exclusion Criteria ALT or AST >5 times ULN eGFR <30 mL/min Interventions RDV 200 mg IV on Day 1, then RDV 100 mg IV once 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 59 years; 64% men; 53% White, 21% Black, 13% Asian, 24% Hispanic/Latinx Coexisting conditions: 26% with 1; 55% with ≥2 13% not on oxygen; 41% on supplemental oxygen; 18% on HFNC oxygen or NIV; 27% on MV or ECMO Median time from symptom onset to randomization: 9 days (IQR 6–12 days) 23% received corticosteroids during study Primary Outcomes Time to clinical recovery: 10 days in RDV arm vs. 15 days in placebo arm (rate ratio for recovery 1.29; 95% CI, 1.12–1.49; P < 0.001) Benefit of RDV 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 HFNC oxygen, NIV, MV, or ECMO at enrollment Secondary Outcomes Improvement in clinical status at Day 15 more likely in RDV arm (OR 1.5; 95% CI, 1.2–1.9; P < 0.001) No difference between arms in mortality by Day 29 Occurrence of SAEs: 25% in RDV arm vs. 32% in placebo arm	Key Limitations Wide range of disease severity among patients; study not powered to detect differences within subgroups Study not powered to detect differences in mortality between arms No data on longer-term morbidity Interpretation In patients with severe COVID-19, RDV reduced the 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 HFNC oxygen, NIV, MV, or ECMO, but the study was not powered to detect differences within subgroups.
CATCO: Multicenter, Open-Label, Pragmatic RCT of Remdesivir in Hospitalized Patients With COVID-19 in Canada²
Key Inclusion Criterion Laboratory-confirmed SARS-CoV-2 infection Key Exclusion Criterion Already receiving RDV Interventions RDV 200 mg IV on Day 0, then RDV 100 mg IV once daily on Days 1–9 (n = 634) Local SOC (n = 647) Primary Endpoint In-hospital mortality Key Secondary Endpoints New need for MV Hospital LOS Incidence of hepatic dysfunction, incidence of need for dialysis, and change in SCr at Day 5	Participant Characteristics Median age 66 years; 60% men; 41% White Median time from symptom onset to randomization: 8 days At entry: 54% on low-flow oxygen 24% on HFNC oxygen 9% on MV Rates of comorbidities were similar between arms. 87% in both arms were receiving corticosteroids at baseline Primary Outcome In-hospital mortality: 19% in RDV arm vs. 23% in SOC arm (relative risk 0.83; 95% CI, 0.67–1.03) Secondary Outcomes New need for MV: 8% in RDV arm vs. 15% in SOC arm (relative risk 0.53; 95% CI, 0.38–0.75) No significant difference between arms in hospital LOS No difference between arms in incidence of new hepatic dysfunction, incidence of need for dialysis, or change in SCr at Day 5	Key Limitations Open-label study Information on comorbidities was not available for 26% of patients. Interpretation RDV did not decrease in-hospital mortality among patients with COVID-19 compared to SOC. Patients who received RDV were less likely to require MV than patients who received SOC.
DisCoVeRy: Open-Label, Adaptive RCT of Remdesivir in Hospitalized Patients With Moderate or Severe COVID-19 in Europe³
Key Inclusion Criteria Laboratory-confirmed SARS-CoV-2 infection Illness of any duration SpO₂ ≤94% on room air or use of supplemental oxygen, HFNC oxygen, 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 Endpoints Mortality by Day 29 Occurrence of SAEs	Participant Characteristics Median age 64 years; 70% men; 69% White 74% with ≥1 coexisting condition 40% received corticosteroids Median time from symptom onset to randomization: 9 days in both arms 61% with moderate disease; 39% with severe disease Primary Outcome 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 Mortality by Day 29: 8% in RDV arm vs. 9% in SOC arm Occurrence of SAEs: 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 WHO 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, Final Report: Multinational, Open-Label, Adaptive RCT in Hospitalized Patients With COVID-19 in 35 Countries⁴
Key Inclusion Criterion Not known to have received any study drug Interventions RDV 200 mg IV on Day 0, then RDV 100 mg IV once daily on Days 1–9 (n = 4,146) Local SOC (n = 4,129) Primary Endpoint In-hospital mortality Key Secondary Endpoint Initiation of MV	Participant Characteristics 46% aged 50–69 years; 22% aged ≥70 years; 63% men Rates of comorbidities were similar between arms At entry: 71% on supplemental oxygen 9% on MV 68% received corticosteroids during study; 4.6% received IL-6 inhibitors Primary Outcome In-hospital mortality: 14.5% in RDV arm vs. 15.6% in SOC arm (rate ratio 0.91; 95% CI, 0.82–1.02; P = 0.12) On MV: 42.1% vs. 38.6% (rate ratio 1.13; 95% CI, 0.89–1.42; P = 0.32) Not on MV but receiving oxygen: 14.6% vs. 16.3% (rate ratio 0.87; 95% CI, 0.76–0.99; P = 0.03) Not on oxygen initially: 2.9% vs. 3.8% (rate ratio 0.76; 95% CI, 0.46–1.28; P = 0.30) Secondary Outcome Initiation of MV: 14.1% in RDV arm vs. 15.7% in SOC arm (rate ratio 0.88; 95% CI, 0.77–1.00; P = 0.04)	Key Limitations Open-label study No data on time from symptom onset to enrollment Data analysis did not separate receipt of low-flow and high-flow oxygen Interpretation There was no benefit of RDV in patients who were on MV at baseline. Compared to SOC, RDV had a modest but statistically significant effect on reducing the risk of death or progression to MV in hospitalized patients who required oxygen.
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-19 in Asia, Europe, and the United States⁵
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 IV once daily for 9 days (n = 193) RDV 200 mg IV on Day 1, then RDV 100 mg IV once 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 were similar across arms. Median age 57 years; 61% men; 58% White 84% required no supplemental oxygen; 15% required low-flow oxygen; 1% required HFNC 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 or CQ: 11%, 8%, 45% LPV/RTV: 6%, 5%, 22% AZM: 21%, 18%, 31% Median duration of therapy: 6 days in 10-day RDV arm vs. 5 days in 5-day RDV arm Primary Outcome Clinical status at Day 11: Significantly better in 5-day RDV arm than in SOC arm (OR 1.65; 95% CI, 1.09–2.48; P = 0.02) No difference 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 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 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 Severe COVID-19 in Asia, Europe, and the United States⁶
Key Inclusion Criteria Laboratory-confirmed SARS-CoV-2 infection Aged ≥12 years 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 IV once daily for 4 days (n = 200) RDV 200 mg IV on Day 1, then RDV 100 mg IV once daily for 9 days (n = 197) Primary Endpoint Clinical status at Day 14, as measured by an OS	Participant Characteristics Median age: 61 years in 5-day RDV arm vs. 62 years in 10-day RDV arm 60% men in 5-day RDV arm; 68% men in 10-day RDV arm Oxygen requirements at baseline for 5-day RDV arm and 10-day RDV arm: None: 17%, 11% Low-flow oxygen: 56%, 54% HFNC oxygen or NIV: 24%, 30% MV or ECMO: 2%, 5% Baseline clinical status worse in 10-day arm than in 5-day arm (P = 0.02) Primary Outcome After adjusting for baseline clinical status: Proportion with clinical improvement at Day 14: 65% in 5-day RDV arm vs. 54% in 10-day RDV arm (P = 0.14)	Key Limitations Open-label study Lack of placebo arm Baseline imbalances in clinical status of patients in 5-day RDV and 10-day RDV 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.
PINETREE: Double-Blind, Placebo-Controlled Trial of Remdesivir for 3 Days in Nonhospitalized Patients With COVID-19 Who Were at High Risk of Disease Progression in Denmark, Spain, the United Kingdom, and the United States⁷
Key Inclusion Criteria Laboratory-confirmed SARS-CoV-2 infection ≤4 days from screening Aged ≥12 years ≥1 risk factor for disease progression or aged ≥60 years Symptom onset ≤7 days from randomization ≥1 ongoing COVID-19 symptom Key Exclusion Criteria COVID-19 vaccination Receipt of supplemental oxygen Previous hospitalization or treatment for COVID-19 Interventions RDV 200 mg IV on Day 1, then RDV 100 mg IV once daily on Days 2 and 3 (n = 279) Placebo (n = 283) Primary Endpoints COVID-19-related hospitalization or death from any cause by Day 28 Occurrence of AEs Key Secondary Endpoint COVID-19-related, medically attended visit or death from any cause by Day 28	Participant Characteristics Mean age 50 years; 30% aged ≥60 years; 52% men; 80% White, 8% Black 62% with DM; 55% with obesity; 48% with HTN Median duration of symptoms before first infusion: 5 days (IQR 3–6 days) Median time from RT-PCR confirmation: 2 days (IQR 1–4 days) Primary Outcomes COVID-19-related hospitalization or death from any cause by Day 28: 2 (0.7%) in RDV arm vs. 15 (5.3%) in placebo arm (HR 0.13; 95% CI, 0.03–0.59; P = 0.008) Occurrence of AEs: 42% in RDV arm vs. 46% in placebo arm Secondary Outcome COVID-19-related, medically attended visit or death from any cause by Day 28: 4 (1.6%) in RDV arm vs. 21 (8.3%) in placebo arm (HR 0.19; 95% CI, 0.07–0.56)	Key Limitations Study halted early due to administrative issues. Vaccinated individuals were excluded. Interpretation 3 consecutive days of IV RDV resulted in an 87% relative reduction in the risk of hospitalization or death when compared to placebo.
Key: AE = adverse event; ALT = alanine transaminase; AST = aspartate aminotransferase; AZM = azithromycin; CQ = chloroquine; CrCl = creatinine clearance; DM = diabetes mellitus; ECMO = extracorporeal membrane oxygenation; eGFR = estimated glomerular filtration rate; HCQ = hydroxychloroquine; HFNC = high-flow nasal cannula; HTN = hypertension; IV = intravenous; IL = interleukin; LOS = length of stay; 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; RT-PCR = reverse transcription polymerase chain reaction; SAE = serious adverse event; SCr = serum creatinine; SOC = standard of care; SpO₂ = oxygen saturation; ULN = upper limit of normal; WHO = World Health Organization

References

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