Remdesivir (RDV) has been shown to shorten time to recovery in hospitalized adults with COVID-19. Some children who develop COVID-19 require hospitalization. Here we characterize the safety profile of RDV in 53 pediatric patients age 28 days to <18 years and describe clinical and virologic outcomes.
CARAVAN (NCT04431453) is an ongoing open-label, single arm study of RDV in hospitalized patients <18 years with PCR-confirmed COVID-19. IV RDV was given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 and 8 (<18y, weight ?40kg) or 5mg/kg on Day 1 followed by 2.5mg/kg daily in Cohorts 2-4 (28 days to <18y, stratified by weight). Safety was assessed by adverse events (AEs) and lab tests (hematology, chemistry, urine, inflammatory, coagulation). Clinical outcomes included improvement on a 7-point ordinal scale, time to discharge, and oxygenation modality. Virologic outcomes included days to confirmed negative SARS-CoV-2 PCR (defined as 2 consecutive negative results).
At enrollment, median (IQR) age was 7y (2, 12) and weight was 24.6 (12.8, 55.1) Kg, 57% were female, 76% required supplemental oxygen, including 23% on invasive ventilation and 34% on high-flow oxygen (Table). Median number of RDV doses was 5 (4,8). Most patients (72%) experienced ?1 AE; most common was constipation (17%). Serious AEs were reported for 21% of patients and none were study-drug related. Two patients with baseline transaminitis had non-serious AE of increased ALT contributing to premature discontinuation. Two patients died within the 30-day study period. Grade ? 3 lab abnormalities were reported in 42%; most common being decreased haemoglobin (n=9) and decreased eGFR levels (n=7). No safety trends related to RDV were apparent. In total, 85% showed clinical improvement on the 7-point ordinal scale by last assessment. Median (IQR) time to discharge was 8 (5, 17) days. By last assessment, 8% required supplemental oxygen, all of whom were invasively ventilated. Time to confirmed negative SARS-CoV-2 PCR CoV-2 PCR was 5 and 7 days from nasal/oropharyngeal samples in cohort 2 and 3, respectively, and not estimable in the other cohorts.
RDV was safe and well tolerated among children 28 days to <18y treated for COVID-19. Overall, no safety trends for RDV were apparent and a high proportion, 85%, had clinical improvement. The study is ongoing with enrolment of full term and preterm neonates pending dose determination.