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.
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 发起方
- 入组人数
- 308
- 试验地点
- 1
- 主要终点
- Time to Clinical recoveryTime to Clinical Recovery (TTCR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years at time of signing Informed Consent Form
- •Laboratory (RT-PCR) confirmed COVID-
- •Lung involvement confirmed with chest imaging
- •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
- •≤8 days since illness onset
- •Willingness of study participant to accept randomization to any assigned treatment arm.
- •Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of study.
排除标准
- •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.
- •Severe liver disease (e.g. Child Pugh score ≥ C, AST>5 times upper limit)
- •SaO2/SPO2≤94% in room air condition, or the Pa02/Fi02 ratio <300mgHg
- •Known allergic reaction to remdesivir
- •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
- •Pregnant or breastfeeding, or positive pregnancy test in a predose examination
- •Will be transferred to another hospital which is not the study site within 72 hours.
- •Receipt of any experimental treatment for COVID-19 within the 30 days prior to the time of the screening evaluation.
研究组 & 干预措施
Remdesivir group
active remdesivir
干预措施: Remdesivir (Drug)
Control group
Placebos matched remdesivir
干预措施: Remdesivir placebo (Drug)
结局指标
主要结局
Time to Clinical recoveryTime to Clinical Recovery (TTCR)
时间窗: 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, 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.
次要结局
- All cause mortality(up to 28 days)
- Time to defervescence (in those with fever at enrolment)(up to 28 days)
- Time to cough reported as mild or absent (in those with cough at enrolment rated severe or moderate)(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,)(up to 28 days)
- Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen(up to 28 days)
- Frequency of requirement for mechanical ventilation(up to 28 days)
- Frequency of respiratory progression(up to 28 days)
- Frequency of requirement for supplemental oxygen or non-invasive ventilation(up to 28 days)
- Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve.(up to 28 days)
- Frequency of serious adverse events(up to 28 days)
研究者
Bin Cao
Professor
China-Japan Friendship Hospital