A Randomized Open-Label Trial of CONvalenscent Plasma for Hospitalized Adults With Acute COVID-19 Respiratory Illness (CONCOR-1)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 940
- 试验地点
- 73
- 主要终点
- Number of Participants Who Were Intubated or Died
研究概览
简要总结
There is currently no treatment available for COVID-19, the acute respiratory illness caused by the novel SAR-CoV-2. Convalescent plasma from patients who have recovered from COVID-19 that contains antibodies to the virus is a potential therapy. On March 25th, 2020, the FDA approved the use of convalescent plasma under the emergency investigational new drug (eIND) category. Randomized trials are needed to determine the efficacy and safety of COVID-19 convalescent plasma for acute COVID-19 infection.
The objective of the CONCOR-1 trial is to determine the efficacy of transfusion of COVID-19 convalescent plasma to adult patients admitted to hospital with COVID-19 infection at decreasing the frequency of in-hospital mortality in patients hospitalized for COVID-19.
It is hypothesized that treating hospitalized COVID-19 patients with convalescent plasma early in their clinical course will reduce the risk of death, and that other outcomes will be improved including risk of intubation, and length of ICU and hospital stay.
This pan-Canadian clinical trial has the potential to improve patient outcomes and reduce the burden on health care resources including reducing the need for ICU beds and ventilators.
详细描述
Problem to be addressed: In December 2019, the Wuhan Municipal Health Committee (Wuhan, China) identified an outbreak of viral pneumonia cases of unknown cause. Coronavirus RNA was quickly identified in some of these patients.This novel coronavirus has been designated SARS-CoV-2, and the disease caused by this virus has been designated COVID-19.Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise [1] in many countries over the coming weeks to months.Global efforts to evaluate novel antivirals and therapeutic strategies to treat COVID-19 have intensified. There is an urgent public health need for rapid development of novel interventions. At present, there is no specific antiviral therapy for coronavirus infections.
Passive immunization:Passive immunization consists in the transfer of antibodies from immunized donor to non-immunized individual in order to transfer transient protection against an infective agent. A physiological example of passive immunization is the transfer of maternal IgG antibodies to the foetus through the placenta to confer humoral protection to newborns in the first years of life. Passive immunization differs from active immunization in which the patient develops their own immune response following contact with the infective agent or vaccine.
Known potential risks and benefits: There is a theoretical risk of antibody-dependent enhancement of infection (ADE) through which virus targeted by non-neutralizing antibodies gain entry into macrophages. Another theoretical risk is that antibody administration to those exposed to SARS-CoV-2 may avoid disease but modify the immune response such that those individuals mount attenuated immune responses, which would leave them vulnerable to subsequent re-infection. Finally, there are risks associated with any transfusion of plasma including transmission of blood transmitted viruses (e.g. HIV, HBV, HCV, etc.), allergic transfusion reactions, including anaphylaxis, febrile non hemolytic transfusion reaction, transfusion related acute lung injury (TRALI), transfusion associated cardiac overload (TACO), and hemolysis should ABO incompatible plasma be administered. Potential benefits of COVID-19 convalescent plasma include improved survival, improvement in symptoms, decreased risk in intubation for mechanical ventilation, decrease risk of intensive care unit (ICU) admission, shortened hospitalization time and suppression of viral load.
Mechanism of action: Transfusion of apheresis frozen plasma (AFP) from COVID-19 convalescent patients allows the transfer of donor neutralizing antibodies directed against SARS-CoV2 antigens to the recipient, thus allowing the generation of passive immunization. Naturally produced human antibody are polyclonal, meaning they are directed against a variety of different viral antigens and epitopes allowing for a general neutralizing effect against the virus rather than focussing on a specific target. Administration of convalescent plasma has been associated with rapid decrease in viral load. It is also possible that passive immunization contributes to improved cell-mediated immunity by favoring the phagocytosis and presentation of viral antigens to host T cells.
Participant recruitment:Only hospitalized COVID-19 patients are eligible so recruitment efforts will be focused on identified consecutive patients admitted to hospital with acute COVID-19 infection. No other external recruitment efforts are planned. At each participating hospital, a process for identifying patients with COVID-19 will be established.
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
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥16 years old (>18 years of age in the United States)
- •Admitted to hospital with confirmed COVID-19 respiratory illness
- •Receiving supplemental oxygen
- •500 mL of ABO compatible convalescent plasma is available
排除标准
- •Onset of respiratory symptoms >12 days prior to randomization
- •Intubated or plan in place for intubation
- •Plasma is contraindicated (e.g. history of anaphylaxis from transfusion)
- •Decision in place for no active treatment
研究组 & 干预措施
Convalescent plasma
~500 mL ABO compatible convalescent apheresis plasma
干预措施: Convalescent plasma (Biological)
Standard of care
Treated as per institutional standard of care.
结局指标
主要结局
Number of Participants Who Were Intubated or Died
时间窗: Day 30
Endpoint of the need for intubation or patient death
次要结局
- Length of Stay in Hospital(Day 90)
- Patient Reported Outcome- Quality-adjusted Life Days(Day 30)
- In-hospital Death(Day 90)
- Time to In-hospital Death(Day 90)
- Death by Day 30(Day 30)
- Length of Stay in Intensive Care Unit (ICU)(Day 30)
- Development of Myocarditis(Day 30)
- Number of Participants With Grade 3, 4, or 5 Serious Adverse Events(Day 30)
- Patient Reported Outcome Using Change in EQ-5D-5L Score(Baseline and Day 30)
- Cost of Intervention and Hospital Stay(Day 30)
- Number of Participants With Grade 3 and 4 Serious Adverse Events(Day 30)
- Number of Participants With CCP Transfusion-associated Adverse Events (AE)(Day 30)
- Time to Intubation or In-hospital Death(Day 30)
- Ventilator-free Days by Day 30(Day 30)
- Need for Renal Replacement Therapy(Day 30)
- Need for Extracorporeal Membrane Oxygenation (ECMO)(Day 30)