A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Severe COVID-19.
Latest Information Update: 19 Jan 2021
At a glance
- Drugs Remdesivir (Primary)
- Indications COVID 2019 infections
- Focus Registrational; Therapeutic Use
- 22 Dec 2020 Data from this and other study (NCT03652363) was used to demonstrate the use of two plots identified to be beneficial for wide use in RCTs, Results published in the Trials.
- 24 May 2020 Results published in the Trials.
- 04 May 2020 According to an Gilead Sciences media release, data from this study will be reviewed by CHMP as a part of rolling review.
Most Recent Events
Trial Overview
Outcome
Purpose
In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the ready availability of remdesvir as a potential antiviral agent, based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with severe COVID-19.
Comments
According to an Gilead Sciences media release, data from this study will be reviewed by CHMP as a part of rolling review.
According to an Gilead Sciences media release, this study in patients with severe disease was terminated early due to low enrollment.
According to Clinicaltrials.gov, trial was terminated due to the epidemic of COVID-19 which has been controlled well in China, no eligible patients can be enrolled at present.
Primary Endpoints
Time to Clinical Improvement (TTCI) [Censored at Day 28]
description: The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 discharged; 6 death) or live discharge from hospital.
Six-category ordinal scale:
6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen;
1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief).
Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
time_frame: up to 28 days [1]
Other Endpoints
Clinical status
description: Clinical status, assessed by the ordinal scale at fixed time points (days 7, 14, 21, and 28).
time_frame: days 7, 14, 21, and 28
Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
description: Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
time_frame: up to 28 days
All cause mortality
time_frame: up to 28 days
Duration (days) of mechanical ventilation
time_frame: up to 28 days
Duration (days) of extracorporeal membrane oxygenation
time_frame: up to 28 days
Duration (days) of supplemental oxygenation
time_frame: up to 28 days
Length of hospital stay (days)
time_frame: up to 28 days
Time to 2019-nCoV RT-PCR negativity in upper and lower respiratory tract specimens
time_frame: up to 28 days
Change (reduction) in 2019-nCoV viral load in upper and lower respiratory tract specimens as assessed by area under viral load curve.
time_frame: up to 28 days
Frequency of serious adverse drug events
time_frame: up to 28 days [2]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID 2019 infections | treatment | - |
Subjects
- Subject Type patients
-
Number
Planned: 453
Actual: 237
- Sex male & female
- Age Group ≥ 18 years; adult
Patient Inclusion Criteria
1. Age ≥18 years at time of signing Informed Consent Form 2. Laboratory (RT-PCR) confirmed COVID-19. 3. Lung involvement confirmed with chest imaging 4. Hospitalized with a SaO2/SPO2≤94% on room air or Pa02/Fi02 ratio <300mgHg 5. ≤12 days since illness onset 6. Willingness of study participant to accept randomization to any assigned treatment arm. 7. Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of study.
Patient Exclusion Criteria
1. Physician makes a decision that trial involvement is not in patients' best interest, or any condition that does not allow the protocol to be followed safely. 2. Severe liver disease (e.g. Child Pugh score ≥ C, AST>5 times upper limit) 3. Pregnant or breastfeeding, or positive pregnancy test in a predose examination 4. Patients with known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis 5. Will be transferred to another hospital which is not the study site within 72 hours. 6. Receipt of any experimental treatment for COVID-19 within the 30 days prior to the time of the screening evaluation.
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04257656 | ClinicalTrials.gov: US National Institutes of Health |
| CAP-China-remdesivir2 | - |
Trial Dates
-
Initiation Dates
Actual : 06 Feb 2020
-
Primary Completion Dates
Planned : 03 Apr 2020
Actual : 30 Mar 2020
-
End Dates
Planned : 01 May 2020
Actual : 10 Apr 2020
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase III
- Location China
- Focus Registrational; Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| RemdesivirPrimary Drug | Intravenous | Infusion |
Remdesivir group
active remdesivir
Drug: Remdesivir (RDV 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.) Other Name: GS-5734
Control group
Placebos matched remdesivir
Drug: Remdesivir placebo (RDV placebo 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.)
Results
Publications
-
Yeming Wang MD, Dingyu Zhang MD. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Internet-Doc 2020;.
Available from: URL: http://link.adisinsight.com/Lx62F -
Cornelius V, Cro S, Phillips R. Advantages of visualisations to evaluate and communicate adverse event information in randomised controlled trials. Trials 2020;21(1):1028.
PubMed | CrossRef Fulltext -
Hanania N, Kerwin E, Pavord I, Kerstjens H, Pascoe S, Peachey G, et al. Step-up to high dose fluticasone furoate in combination with long-acting bronchodilator in inadequately controlled asthma: the CAPTAIN study. AAAAI-2020 2020; abstr. 072.
Available from: URL: http://annualmeeting.aaaai.org/ -
Wang Y, Zhou F, Zhang D, Zhao J, Du R, Hu Y, et al. Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial. Trials 2020;21(1):422.
PubMed | CrossRef Fulltext
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Yeming Wang, Doctor
wwyymm_love@163.com
show details
|
Bin Cao | China |
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| Bin Cao | Beijing, Beijing | China |
| Capital Medical University |
-
|
-
|
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 22 Dec 2020 | Results | Data from this and other study (NCT03652363) was used to demonstrate the use of two plots identified to be beneficial for wide use in RCTs, Results published in the Trials. Updated 19 Jan 2021 |
| 24 May 2020 | Results | Results published in the Trials. Updated 11 Jun 2020 |
| 04 May 2020 | Other trial event | According to an Gilead Sciences media release, data from this study will be reviewed by CHMP as a part of rolling review. Updated 06 May 2020 |
| 29 Apr 2020 | Endpoint not met | Primary endpoint (Time to Clinical Improvement (TTCI)) has not been met. Updated 30 Apr 2020 |
| 29 Apr 2020 | Results | Results published in the Lancet. Updated 30 Apr 2020 |
| 16 Apr 2020 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 16 Apr 2020 |
| 10 Apr 2020 | Other trial event | According to an Gilead Sciences media release, this study in patients with severe disease was terminated early due to low enrollment. The company awaits the publication of these data to enable an in-depth review of the results. Updated 16 Apr 2020 |
| 10 Apr 2020 | Status change - discontinued | Status changed from recruiting to discontinued, according to an Gilead Sciences media release. Updated 16 Apr 2020 |
| 16 Mar 2020 | Results | Results presented at the 2020 Annual Meeting of the American Academy of Allergy, Asthma and Immunology Updated 30 Apr 2020 |
| 20 Feb 2020 | Other trial event | Planned number of patients changed from 452 to 453. Updated 25 Feb 2020 |
| 14 Feb 2020 | New trial record | New trial record Updated 14 Feb 2020 |
References
-
Yeming Wang MD, Dingyu Zhang MD. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Internet-Doc 2020;.
Available from: URL: http://link.adisinsight.com/Lx62F -
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Cornelius V, Cro S, Phillips R. Advantages of visualisations to evaluate and communicate adverse event information in randomised controlled trials. Trials 2020;21(1):1028.
PubMed | CrossRef Fulltext -
European Medicines Agency. EMA starts rolling review of remdesivir for COVID-19. Media-Rel 2020;.
Media Release -
Hanania N, Kerwin E, Pavord I, Kerstjens H, Pascoe S, Peachey G, et al. Step-up to high dose fluticasone furoate in combination with long-acting bronchodilator in inadequately controlled asthma: the CAPTAIN study. AAAAI-2020 2020; abstr. 072.
Available from: URL: http://annualmeeting.aaaai.org/ -
Wang Y, Zhou F, Zhang D, Zhao J, Du R, Hu Y, et al. Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial. Trials 2020;21(1):422.
PubMed | CrossRef Fulltext -
Gilead Sciences. Data on 53 Patients Treated With Investigational Antiviral Remdesivir Through the Compassionate Use Program Published in New England Journal of Medicine. Media-Rel 2020;.
Media Release
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