Covid-19 living Data

Remdesivir 5 days vs Remdesivir 10 days (RCT)

Hospitalized patients

FOREST PLOTS -2022-10-11

Studies description

Trial NCT04292899
Publication Goldman JD, N Engl J Med (2020) (published paper)
Dates: 06mar2020 to 26mar2020
Funding: Private (Gilead Sciences)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / United States, Italy, Spain, Germany, Hong Kong, Singapore, South Korea, and Taiwan Follow-up duration (days): 40
Inclusion criteria	We enrolled hospitalized patients who were at least 12 years of age who had SARS-CoV-2 infection confirmed by polymerase-chain-reaction assay within 4 days before randomization. Eligible patients had radiographic evidence of pulmonary infiltrates and either had oxygen saturation of 94% or less while they were breathing ambient air or were receiving supplemental oxygen.
Exclusion criteria	Patients who were receiving mechanical ventilation and extracorporeal membrane oxygenation (ECMO) at screening were excluded, as were patients with signs of multiorgan failure. Exclusion criteria included alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 5 times the upper limit of the normal range or estimated creatinine clearance of less than 50 ml per minute (by the Cockcroft–Gault formula). Patients receiving concurrent treatment (within 24 hours before the start of trial treatment) with other agents with putative activity against Covid-19 were excluded.
Interventions
	Treatment Remdesivir 5 days 200 mg IV on day 1 followed by 100 mg once a day for the next 4 days.
	Control Remdesivir 10 days 200 mg IV on day 1 followed by 100 mg once a day for the next 9 days.
Participants
	Randomized participants : Remdesivir 10 days=200 Remdesivir 5 days=202
	Characteristics of participants N= 402 Mean age : NR 253 males Severity : Mild: n=0 / Moderate: n=275 / Severe: n=109 Critical: n=13
Primary outcome
	In the register The odds ratio for improvement on a 7 point ordinal scale on day 14
	In the report Clinical status assessed on day 14 on a 7-point ordinal scale consisting of the following categories: 1, death; 2, hospitalized, receiving invasive mechanical ventilation or ECMO; 3, hospitalized, receiving noninvasive ventilation or high-flow oxygen
Documents avalaible	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 all available versions of the published/pre-print article, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. The primary outcome in the report reflects the primary outcome indicated in the registry. The trial registration describes additional trial arms as an extension to the study (the additional arms would enroll participants after enrollment to Part A, that includes the two arms presented in the published report, was complete). The extraction was updated on January 20th, 2021 based on results published on Clinicaltrials.gov on December 31st, 2020.

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 200 mg IV infusion on day-1 followed by 100 mg once a day for next 9 days 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=396 Remdesivir 10 days=197 Remdesivir 5 days=199 Standard care=200
	Characteristics of participants N= 992 Mean age : NR 475 males Severity : Mild: n=660 / Moderate: n=111 / Severe: n=6 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 stat
	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 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