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.
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.
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. 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.
Jin Yin-tan hospital
Wuhan, Hubei, China