A Trial of Remdesivir in Adults With Mild and Moderate COVID-19

NCT ID: NCT04252664

Last Updated: 2020-04-15

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE3
• Total Enrollment: 308 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-12
• Study Completion Date: 2020-04-27

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 (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.

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 (SARS-CoV-2) 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 COVID-19 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 COVID-19 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 COVID-19 to become pandemic and/or endemic in human populations.

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.

Conditions

COVID-19; SARS-CoV-2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Remdesivir group

active remdesivir

Group Type: EXPERIMENTAL

Remdesivir

Intervention Type: DRUG

RDV 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.

Control group

Placebos matched remdesivir

Group Type: PLACEBO_COMPARATOR

Remdesivir placebo

Intervention Type: DRUG

RDV placebo 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.

Interventions

Remdesivir

RDV 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

GS-5734

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Bin Cao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Jin Yin-tan hospital

Wuhan, Hubei, China

Countries

China

References

Grundeis F, Ansems K, Dahms K, Thieme V, Metzendorf MI, Skoetz N, Benstoem C, Mikolajewska A, Griesel M, Fichtner F, Stegemann M. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2023 Jan 25;1(1):CD014962. doi: 10.1002/14651858.CD014962.pub2.

Reference Type: DERIVED

PMID: 36695483 (View on PubMed)

Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.

Reference Type: DERIVED

PMID: 34350582 (View on PubMed)

Other Identifiers

CAP-China remdesivir 1

Identifier Type: -

Identifier Source: org_study_id