A Randomized, Prospective, Open Label Clinical Trial on the Use of Convalescent Plasma Compared to Best Supportive Care in Patients With Severe COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 106
- 试验地点
- 15
- 主要终点
- Composite endpoint of survival and no longer fulfilling criteria of severe COVID-19.
研究概览
简要总结
This is a randomized, prospective, multicenter, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.
The aim of the study is to explore the therapeutic effect of convalescent plasma transfusions on the survival and course of disease of patients with severe COVID-19. Convalescent plasma will be collected from recovered COVID-19 patients.
Patients with severe COVID-19 will be randomly assigned to two groups. Patients in the treatment group will receive covalescent plasma (250 - 325 ml) on days 1, 3 and 5. Patients in the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline, patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19.
Fifty-three patients will be included in each group. Data of each patient will be collected until discharge but nor longer than day 60.
详细描述
This is a randomized, prospective, multicentre, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.
The primary Endpoint is a dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19 within 21 days after randomization. All criteria must be met in order to fulfil the primary endpoint.
Key secondary endpoints are time to clinical improvement (defined as time from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement), the frequency and severity of adverse events and the case fatality rate on day 21, 35 and 60. Further secondary endpoints refer to the course of anti-SARS-CoV-2 antibodies in plasma donors and treated patients and the impact of donor criteria on the effectiveness of plasma units.
Patients with severe COVID-19 defined by a respiratory rate ≥ 30 breaths / minute under ambient air or the requirement of any type of ventilation support or the need for ICU treatment can be included in the trial. It is planned to enrol 106 patients. Patients will be stratified according to ventilation support and/or extracorporeal oxygenation and/or ICU treatment and will be equally asigned to two groups. The treatment group receives convalescent plasma (250 - 325 ml) on day 1, 3 and 5 and the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline (i.e. day 0), patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19. A patient switching from the control group to convalescent plasma group because of progressive COVID-19 on day 14 will be considered as failure of the primary endpoint at final evaluation of the primary endpoint on day 21.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with SARS-CoV-2 infection and
- •age ≥ 18 years and ≤ 75 years
- •SARS-CoV-2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap)
- •severe disease defined by at least one of the following:
- •respiratory rate ≥ 30 breaths / minute under ambient air
- •requirement of any type of ventilation support
- •needs ICU treatment
- •Written informed consent by patient or legally authorized representative
排除标准
- •Accompanying diseases other than COVID-19 with an expected survival time of less than 12 months.
- •Previous treatment with any SARS-CoV-2-convalescent plasma
- •In the opinion of the clinical team, progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatment
- •Interval > 72 hours since start of ventilation support
- •Not considered eligible for extracorporeal oxygenation support (even in case of severe ARDS according to Berlin classification with Horovitz-Index < 100 mg Hg)
- •Chronic obstructive lung disease (COPD), stage 4
- •Lung fibrosis with UIP pattern in CT und severe emphysema
- •Chronic heart failure NYHA >= 3 and/or pre-existing reduction of left ventricular ejection fraction to ≤ 30%
- •Shock of any type requiring ≥ 0.5 µg/kg/min noradrenaline (or equivalent) or requiring more than two types of vasopressor medication for more than 8 hours
- •Liver cirrhosis Child C
- •Liver failure: Bilirubin > 5xULN and elevation of ALT /AST (at least one >10xULN).
- •Any history of adverse reactions to plasma proteins
- •Known deficiency of immunoglobulin A
- •Breastfeeding women
- •Volume overload until sufficiently treated
- •Participation in another clinical trial with an investigational medicinal product
研究组 & 干预措施
Convalescent plasma
Convalescent plasma transfusion on day 1, 3 and 5.
干预措施: Convalesscent Plasma (Drug)
结局指标
主要结局
Composite endpoint of survival and no longer fulfilling criteria of severe COVID-19.
时间窗: Day 21
Dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. All criteria must be met in order to fulfil the primary endpoint.
次要结局
- Time to clinical improvement(day 0 to discharge within a 60 day period)
- Frequency and severity of adverse events by CTCAE v5.0, (Key secondary endpoint)(day 0 to discharge within a 60 day period)
- Case fatality rate(on day 21, 35 and 60)
- Length of hospital stay Length of hospital stay (if applicable)(day 0 to 60)
- Duration of ventilation support / ECMO(day 0 to 60)
- Predictive value of comorbidities(day 0 to 60)
- Predictive value of coagulation markers(day 0 to 60)
- Predictive value of inflamation(day 0 to 60)
- Amount of Plasma Units that could be collected for the clinical trial(through study completion, an average of 8 months)
- Titer of anti-SARS-CoV-2 in transfused plasma units(any plasmaphereseis, through study completion, an average of 8 months)
- Impact of donor characteristics on anti-SARS-CoV-2 humoral response(up to 60 days)
- Length of stay in ICU(day 0 to 60)
- Time until negative SARS-CoV-2 PCR (nasopharyngeal sample)(day 0 to 60)
- Percentage of former COVID-19 patients willing to donate qualifying for plasma donation.(through study completion, an average of 8 months)
- Course of anti-SARS-CoV-2 titer in both patient groups at different time points related to transfusion of convalescent plasma(up to 60 days)
- Correlation of anti-SARS-CoV-2 titer in transfused plasma units and primary and key secondary outcomes.(day 0 to 60)
- Effect of timing of plasma transfusions(day 0 to 60)
- Long term survival(15 month)
- Frequency of long COVID-19(15 month)
- Resolution of pneumonia and functional recovery(15 month)
- Patient Reported Outcome: FACIT Fatigue Score(15 month)
- Patient Reported Outcome: FACIT Dyspnea Score(15 month)
- Patient Reported Outcome: EQ-5D-5L visual Scale(15 month)
- Patient Reported Outcome:EQ-5D-5L cross walk(15 month)
- Laboratory markers: D-Dimers(15 month)
- Laboratory markers: Fibrinogen(15 month)
- Laboratory markers: CRP(15 month)
- Laboratory markers: Ferritin(15 month)
- Laboratory markers: IL-6(15 month)
- Severity of long COVID-19(15 month)
- Duration of long COVID-19(15 month)