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.
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 infection with
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 illness appears to be wide, encompassing asymptomatic
infection, a mild upper respiratory tract infection, and severe viral pneumonia with
respiratory failure and even death. Although the per infection risk of severe disease remains
to be determined, case-fatality risk of 11-14% has been reported in several initial studies
of seriously ill patients and case-fatality has been estimated approximately at 2% overall.
Also the large number of cases in Wuhan has resulted in a large number of patients
hospitalised with pneumonia requiring supplemental oxygen and sometimes more advance
ventilator support.
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, speed
recovery, and reduce the requirements for intensive supportive care and prolonged
hospitalisation.
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.
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.
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.
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.
Bin Cao
Beijing, Beijing, China