Trial NCT04292730
Publication Spinner CD, JAMA (2020) (published paper)
Dates: 2020-03-15 to 2020-04-18
Funding: Private (Gilead Sciences)
Conflict of interest: Yes

Methods
RCT
Blinding: Unblinded
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. Aged >=18 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
Remdesivir 10 days
200 mg IV infusion on day-1 followed by 100 mg once a day for next 9 days

Remdesivir 5 days
200 mg IV infusion on day-1 followed by 100 mg once a day for next 4 days
Control
Standard care

Participants
Randomized
participants :
Remdesivir 10 days=197
Remdesivir 5 days=199
Standard care=200
Characteristics of participants
N= 596
Mean age : NR
357 males
Severity : Mild: n=491 / Moderate: n=88 / Severe: n=5 Critical: n=0
Number of vaccinated participants: NR
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 stat
In the report
Clinical status assessed by a 7-point ordinal scale on Day 11
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:
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