Trial NCT04292730
Publication Spinner CD, JAMA, 2020
Dates: 3/15/2020 to 4/18/2020
Funding: Private (Gilead Sciences)
| Methods | |
| RCT | |
| Location :
Multicenter / Multinational Follow-up duration (days): 28 | |
| Inclusion criteria | Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
1. Willing and able to provide written informed consent (participants 18 years of age) or assent (participants 12 and < 18 years of age) prior to performing study procedures. For participants 12 and < 18 years of age, a parent or legal guardian willing and able to provide written informed consent prior to performing study procedures 2. Aged18 years (at all sites), or aged 12 and < 18 years of age weighing 40 kg (where permitted according to local law and approved nationally and by the relevant institutional review board [IRB] or independent ethics committee [IEC]) 3. SARS-CoV-2 infection confirmed by PCR¢ 4 days before randomization 4. Currently hospitalized and requiring medical care for COVID-19 5. SpO2 > 94% on room air at screening 6. Radiographic evidence of pulmonary infiltrates 7. Men and women of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. |
| Exclusion criteria | Patients who meet any of the following exclusion criteria are not to be enrolled in this study:
1. Participation in any other clinical trial of an experimental agent treatment for COVID-19 2. Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 < 24 hours prior to study drug dosing Remdesivir (RDV; GS-5734TM) 3. Requiring mechanical ventilation at screening 4. ALTorAST>5xULN 5. Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ??? 18 years of age and Schwartz Formula for participants < 18 years of age 6. Positive pregnancy test 7. Breastfeeding woman 8. Known hypersensitivity to the study drug, the metabolites, or formulation excipient |
| Interventions | |
| Treatment 1 Remdesivir 5 days (200mg loading dose D1 then 100mg D2-D5/NA) Co-Intervention: Standard care Duration : 5 days | |
| Control Standard care (NA/NA) Co-Intervention: Standard care Duration : NA | |
| Treatment 3 Remdesivir 10 days (200mg loading dose D1 then 100mg D2-D10/NA) Co-Intervention: Standard care Duration : 10 days | |
| Participants | |
| Randomized 596 participants n1=199/ n2=200/ n3=197 | |
| Characteristics of participants N=596 Mean age : NR 357 males Severity : Mild: n=491 / Moderate: n=88/ Severe: n=5 Critical: n=0 | |
| Primary outcome | |
| In the register The Odds of Ratio for Improvement on a 7-point Ordinal Scale on Day 11 [ Time Frame: Day 11 ] The odds ratio represents the odds of improvement in the ordinal scale between the treatment groups. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flo | |
| In the report Clinical status assessed by a 7-point ordinal scale on Day 11 | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the published article, the study registry, protocol, SAP and supplementary files were used in data extraction and risk of bias assessment. This is a report on a multinational 3 arm RCT in Phase A and Phase B is ongoing. Quote: "In addition, a non-randomized extension phase was added in which up to 1000 additional patients could be enrolled to receive remdesivir; the results of the extension phase will be the subject of a subsequent report". The target sample size specified in the registry 1113 was not yet achieved. There is no change from the trial registration in the intervention and control treatments. Secondary outcomes in the report are not specified in the trial registry however they are congruent with the protocol. Quote: "The protocol was amended on March 15, 2020, on the basis of emerging understanding of the clinical presentation and assessment of COVID-19. The age limit for eligibility was lowered from 18 years to 12 years and the minimum temperature requirement was eliminated. The primary end point in the original protocol was the proportion of patients discharged by day 14 of the study. This was amended to assessment of clinical status on a 7-point ordinal scale by day 11. |