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A Phase 3 Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Mild and Moderate COVID-19.

Trial Profile

A Phase 3 Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Mild and Moderate COVID-19.

Status: Suspended
Phase of Trial: Phase III

Latest Information Update: 10 Mar 2021

At a glance

  • Drugs Remdesivir (Primary)
  • Indications COVID 2019 infections
  • Focus Therapeutic Use
  • Most Recent Events

    • 10 Mar 2021 Results (n=1005) assessing whether remdesivir was associated with worsening renal function in hospitalized patients with moderate COVID-19, presented at the 28th Conference on Retroviruses and Opportunistic Infections
    • 25 Oct 2020 Results (n=584) presented at the IDWeek 2020
    • 13 Apr 2020 Status changed from recruiting to suspended.

Trial Overview

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 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 mild or moderate COVID-19.

Comments

According to clinical.gov, trial was suspended due to the epidemic of COVID-19 which has been controlled well at present, no eligible patients can be recruitted.

Primary Endpoints

Time to Clinical recoveryTime to Clinical Recovery (TTCR)

description: TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first.
Normalisation and alleviation criteria:
Fever - <37°C,
Respiratory rate - ≤24/minute on room air,
Oxygen saturation - >94% on room air,
Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
time_frame: up to 28 days

Other Endpoints

All cause mortality

description: baseline SpO2 during screening, PaO2/FiO2 300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
time_frame: up to 28 days

Frequency of respiratory progression

description: Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.
time_frame: up to 28 days

Time to defervescence (in those with fever at enrolment)

time_frame: up to 28 days

Time to cough reported as mild or absent (in those with cough at enrolment rated severe or moderate)

time_frame: up to 28 days

Time to dyspnea reported as mild or absent (on a scale of severe, moderate, mild absent, in those with dyspnoea at enrolment rated as severe or moderate,)

time_frame: up to 28 days

Frequency of requirement for supplemental oxygen or non-invasive ventilation

time_frame: up to 28 days

Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen

time_frame: up to 28 days

Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve.

time_frame: up to 28 days

Frequency of requirement for mechanical ventilation

time_frame: up to 28 days

Frequency of serious adverse events

time_frame: up to 28 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 308

  • 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. Hospitalised with: - Fever - ≥36.7℃ -axilla or Oral temperature ≥ 38.0 ℃ or ≥38.6°C tympanic or rectal or - And at least one of Respiratory rate >24/min Or Cough 5. ≤8 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. SaO2/SPO2≤94% in room air condition, or the Pa02/Fi02 ratio <300mgHg 4. Known allergic reaction to remdesivir 5. 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 6. Pregnant or breastfeeding, or positive pregnancy test in a predose examination 7. Will be transferred to another hospital which is not the study site within 72 hours. 8. 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
NCT04252664 ClinicalTrials.gov: US National Institutes of Health
CAP-China-remdesivir1 -

Organisations

  • Affiliations Gilead Sciences

Trial Dates

  • Initiation Dates

    Planned : 05 Feb 2020

    Actual : 12 Feb 2020

  • Primary Completion Dates

    Planned : 10 Apr 2020

  • End Dates

    Planned : 27 Apr 2020

Substudies/Extensions

study has extension phase, receiving 10d of RDV.

Other Details

  • Design multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location China
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
RemdesivirPrimary Drug Intravenous Infusion

receive RDV (5 or 10 days) or standard of care (SOC). RDV dosed intravenously at 200 mg on day 1, 100 mg daily thereafter

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

Therapeutic efficacy

Interim results of the randomised, controlled, double blind phase III CAP-China remdesivir 1 trial demonstrated that remdesivir for up to 5 days was superior to standard of care (SoC) in improving the clinical status by day 11 in patients (n = 584) with mild or moderate COVID-2019 infections. By day 11, two-point improvement on the ordinal scale occurred in 70% of patients in the 5 day remdesivir arm, 65% in the 10 day remdesivir arm, and 61% in the SoC arm. Patients in the 5 day remdesivir arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65; 95% confidence interval [CI]: 1.09-2.48; p = 0.017). The OR of improvement for the 10 day remdesivir arm compared to SoC was 1.31 (95% CI: 0.88-1.95]; p = 0.183). This improvement in the 5 day remdesivir arm over the SOC arm was noted from day 6 through day 11. A peak of discharge corresponding with the assigned treatment duration of remdesivir was observed, with increased discharges at day 6 in the 5 day remdesivir arm and at day 11 in the 10 day remdesivir arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n = 19, 10%) versus the 5 day remdesivir (n = 7, 4%) and 10 day remdesivir (n = 9, 5%) arms.

Adverse events

Results from the phase III CAP-China remdesivir 1 trial demonstrated that remdesivir was well tolerated with grade 3 and grade 4 adverse events compared to fewer serious adverse events in 5 day and 10 day arm. Most common adverse events include nausea, headache and hypokalemia. Incidence of adverse events leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. No statistically significant change was observed in renal and liver function tests between the remdesivir 5 day and 10 day groups compared to the standard of care only group at day 14 [2] . The further analysis of remdesivir effect on renal function in patients with COVID-19 infections demonstrated that patients treated with remdesivir (n=822) reported less frequent acute kidney injury events, compared with the patients receiving standard of care treatment (n=183) (7% vs 10%, p=0.03). After adjustment for age, remdesivir was not significantly associated with the risk of acute kidney injury compared to standard of care (RR=0.66; 95% CI 0.40, 1.09). Patients with baseline estimated glomerular filtration rate (eGFR) >90 ml/min reported more acute kidney injury events, with few events occurring in patients with a baseline eGFR 50-59 ml/min. At day 14, in patients with stage 3 acute kidney injury, creatinine values returned to baseline after treatment with remdesivir (n=2, 0.2%), while it remained elevated in patients receiving standard of care treatment (n=4, 2%). No difference in acute kidney injury was observed between treatment arms in patients with a history of chronic kidney disease (remdesivir: n=6 [12%] vs standard of care: n=2 [40%]; p=0.14). The open-label trial evaluated 1005 patients with similar creatinine and eGFR values in both the treatment arms, collected through day 14 [3]

Publications

  1. Criner GJ, Ahn MY, Huhn G, Subramanian A, Lumbreras C, Schmiedel S, et al. Safety of Remdesivir vs Standard Care in Patients with Moderate Covid-19. IDW-2020 2020; abstr. 561.

    Available from: URL: https://www.eventscribe.net/2020/IDWeek/ajaxcalls/PosterInfo.asp?efp=VFhWUUpXVFA2ODg4&PosterID=291464&rnd=0.1582002
  2. Ogbuagu O, Tashima KT, FGunthard H, McPhail M, Sanyal AJ, Elboudwarej E, et al. ACUTE KIDNEY INJURY IN PATIENTS WITH MODERATE COVID-19 TREATED WITH RDV VERSUS S o C. CROI-2021 2021; abstr. 395.

    Available from: URL: http://www.croiconference.org/

Authors

Author Total Publications First Author Last Author
Aberg JA 2 - 1
Ahn MY 1 - -
Brainard D 1 - -
Brainard DM 1 - -
Cao H 1 - -
Castagna A 1 - -
Chen Y-S 1 - -
Chokkalingam A 1 - -
Chokkalingam AP 1 - -
Criner GJ 1 1 -
Elboudwarej E 1 - -
FGunthard H 1 - -
Gottlieb RL 1 - -
Gunthard H 1 - -
Huhn G 1 - -
Hyland RH 1 - -
Lumbreras C 1 - -
McPhail M 1 - -
Nicastri E 1 - -
Ogbuagu O 1 1 -
Osinusi A 1 - -
Osinusi AO 1 - -
Sanyal AJ 1 - -
Sanz-Moreno DJ 1 - -
Schmiedel S 1 - -
SenGupta D 1 - -
Subramanian A 1 - -
Suri V 1 - -
Tan SK 1 - -
Tashima KT 1 - -
Telep LH 1 - -
Tian YH 1 - -
Tsang OT-Y 1 - 1
Wang H 1 - -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Bin Cao, Professor
+01084206264 caobin@zryhyy.com.cn
show details
-
Yeming Wang, Doctor
-
Ying Liu Jin Yin-tan hospital China

Centres

Centre Name Location Trial Centre Country
-
-
-
Capital Medical University
-
-
Chinese Academy of Medical Sciences
-
-
Jin Yin-tan hospital Wu Han, Hubei China

Trial History

Event Date Event Type Comment
10 Mar 2021 Results Results (n=1005) assessing whether remdesivir was associated with worsening renal function in hospitalized patients with moderate COVID-19, presented at the 28th Conference on Retroviruses and Opportunistic Infections Updated 20 Apr 2021
25 Oct 2020 Results Results (n=584) presented at the IDWeek 2020 Updated 20 Apr 2021
16 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 16 Apr 2020
13 Apr 2020 Status change - suspended Status changed from recruiting to suspended. Updated 16 Apr 2020
20 Feb 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 25 Feb 2020
12 Feb 2020 New trial record New trial record Updated 12 Feb 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Criner GJ, Ahn MY, Huhn G, Subramanian A, Lumbreras C, Schmiedel S, et al. Safety of Remdesivir vs Standard Care in Patients with Moderate Covid-19. IDW-2020 2020; abstr. 561.

    Available from: URL: https://www.eventscribe.net/2020/IDWeek/ajaxcalls/PosterInfo.asp?efp=VFhWUUpXVFA2ODg4&PosterID=291464&rnd=0.1582002
  3. Ogbuagu O, Tashima KT, FGunthard H, McPhail M, Sanyal AJ, Elboudwarej E, et al. ACUTE KIDNEY INJURY IN PATIENTS WITH MODERATE COVID-19 TREATED WITH RDV VERSUS S o C. CROI-2021 2021; abstr. 395.

    Available from: URL: http://www.croiconference.org/
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