A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Severe COVID-19.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 237
- 试验地点
- 1
- 主要终点
- Time to Clinical Improvement (TTCI) [Censored at Day 28]
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 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.
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 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.
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
- •Hospitalized with a SaO2/SPO2≤94% on room air or Pa02/Fi02 ratio <300mgHg
- •≤12 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)
- •Pregnant or breastfeeding, or positive pregnancy test in a predose examination
- •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
- •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 Improvement (TTCI) [Censored at Day 28]
时间窗: up to 28 days
The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
次要结局
- Clinical status(days 7, 14, 21, and 28)
- Time to 2019-nCoV RT-PCR negativity in upper and lower respiratory tract specimens(up to 28 days)
- Change (reduction) in 2019-nCoV viral load in upper and lower respiratory tract specimens as assessed by area under viral load curve.(up to 28 days)
- Frequency of serious adverse drug events(up to 28 days)
- Duration (days) of extracorporeal membrane oxygenation(up to 28 days)
- Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.(up to 28 days)
- All cause mortality(up to 28 days)
- Duration (days) of mechanical ventilation(up to 28 days)
- Duration (days) of supplemental oxygenation(up to 28 days)
- Length of hospital stay (days)(up to 28 days)
研究者
Bin Cao
Professor
China-Japan Friendship Hospital