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Mild/Moderate 2019-nCoV Remdesivir RCT

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ClinicalTrials.gov Identifier: NCT04252664
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : February 24, 2020
Sponsor:
Collaborator:
Chinese Academy of Medical Sciences
Information provided by (Responsible Party):
Bin Cao, China-Japan Friendship Hospital

Tracking Information
First Submitted Date  ICMJE January 31, 2020
First Posted Date  ICMJE February 5, 2020
Last Update Posted Date February 24, 2020
Actual Study Start Date  ICMJE February 12, 2020
Estimated Primary Completion Date April 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2020)
Time to Clinical recoveryTime to Clinical Recovery (TTCR) [ Time Frame: up to 28 days ]
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. Normalisation and alleviation criteria:
  • Fever - ≤36.9°C or -axilla, ≤37.2 °C oral,
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2020)
Rate of composite advers outcomes [ Time Frame: 14 days ]
Defined as SPO2≤ 94% without oxygen supplementation, PaO2/FiO2 <300mmHg or a respiratory rate ≤24 breaths per min without supplemental oxygen
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2020)
  • All cause mortality [ Time Frame: up to 28 days ]
    baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
  • Frequency of respiratory progression [ Time Frame: up to 28 days ]
    Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2020)
  • time to recovery [ Time Frame: 28 days ]
    Clinical recovery was defined as sustained (48 hours) alleviation of illness based on symptom scores (fever, cough, diarrhea, myalgia, dyspnea) all being absent and no evidence for progression (newly-presented dyspnea, SpO2 decline ≥3%, respiratory rate ≥ 24 breaths per min without supplemental oxygen).
  • rate of no fever [ Time Frame: 14 days ]
  • rate of no cough [ Time Frame: 14 days ]
  • rate of no dyspnea [ Time Frame: 14 days ]
  • rate of no requring supplemental oxygen [ Time Frame: 14 days ]
  • rate of undectable viral RNA [ Time Frame: 14 days ]
  • rate of mechanical ventilation [ Time Frame: 28 days ]
  • rate of ICU admission [ Time Frame: 28 days ]
  • rate of serious adverse event [ Time Frame: 28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mild/Moderate 2019-nCoV Remdesivir RCT
Official Title  ICMJE 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 2019-nCoV Respiratory Disease.
Brief Summary

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 (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay.

Given no specific antiviral therapy for 2019-nCoV infection 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 2019-nCoV respiratory disease.

Detailed Description

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 (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay.

Whilst the outbreak is likely to have started from a zoonotic transmission event associated with a large seafood market that also traded in live wild animals, it soon became clear that person-to-person transmission was also occurring. The number of cases of infection with 2019-nCoV identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally. Mathematical models of the expansion phase of the epidemic suggested that sustained person-to-person transmission is occurring, and the R-zero is substantially above 1, the level required for a self-sustaining epidemic in human populations.

The clinical spectrum of 2019-nCoV infection appears to be wide, encompassing asymptomatic infection, a mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and even death. Although the per infection risk of severe disease remains to be determined, and may differ from the initial reports of 10-15%, the large number of cases in Wuhan has resulted in a large number of patients hospitalised with pneumonia. Progression from prodromal symptoms (usually fever, fatigue, cough) to severe pneumonia requiring supplementary oxygen support, mechanical ventilation, or in some cases ECMO appears to occur most commonly during the second week of illness in association with persistent viral RNA detection. This provides a window of opportunity to test candidate antiviral therapeutics.

This new coronavirus, and previous experiences with SARS and MERS-CoV, highlight the need for therapeutics for human coronavirus infections that can improve clinical outcomes, reduce risk of disease progression, speed recovery, and reduce the requirements for intensive supportive care and prolonged hospitalisation. In addition, treatments for mild cases to reduce the duration of illness and infectivity may also be of value were 2019-nCoV to become pandemic and/or endemic in human populations.

Given no specific antiviral therapy for 2019-nCoV infection 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 2019-nCoV respiratory disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE 2019-nCoV
Intervention  ICMJE
  • 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
  • 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.
Study Arms  ICMJE
  • Experimental: Remdesivir group
    active remdesivir
    Intervention: Drug: Remdesivir
  • Placebo Comparator: Control group
    Placebos matched remdesivir
    Intervention: Drug: Remdesivir placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 3, 2020)
308
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2020)
270
Estimated Study Completion Date  ICMJE April 27, 2020
Estimated Primary Completion Date April 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥18 years at time of signing Informed Consent Form
  2. Laboratory (RT-PCR) confirmed infection with 2019-nCoV.
  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.

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 2019-nCoV (off-label, compassionate use, or trial related) within the 30 days prior to the time of the screening evaluation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bin Cao, Professor +01084206264 caobin@zryhyy.com.cn
Contact: Yeming Wang, Doctor
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04252664
Other Study ID Numbers  ICMJE CAP-China remdesivir 1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Bin Cao, China-Japan Friendship Hospital
Study Sponsor  ICMJE Capital Medical University
Collaborators  ICMJE Chinese Academy of Medical Sciences
Investigators  ICMJE Not Provided
PRS Account Capital Medical University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP