Emergency Evaluation of Convalescent Plasma for Ebola Viral Disease (EVD) in Guinea
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 606
- 试验地点
- 1
- 主要终点
- Survival at Day 14 After Start of Intervention
研究概览
简要总结
This is an emergency, phase 2/3, open-label, non-randomized, clinical trial that will evaluate Convalescent Plasma (CP) added to standardized supportive care (SC) in patients with confirmed Ebola Virus Disease (EVD). No patient will be refused CP when compatible products are available and all efforts will be made to maximize CP availability during the study. EVD patients recruited during the period before CP becomes available or for whom no compatible CP is available will be given SC and will be followed for study outcomes. Data from these SC patients will be the used as comparator in the analysis of the study. The primary objective of the study is to assess if CP + SC improves the 14 day survival of patients, compared to SC alone.
The Investigators aim to enroll a total number of 130 - 200 patients who will be treated treated with CP assuming equal numbers of patients treated with SC alone. If there would be insufficient patients treated with SC, patients treated at the research site prior to study start may be included in the comparison group.
Patients will be recruited in the Ebola Treatment centre managed by Medecins Sans Frontieres (MSF) in Conakry, Guinea. All patients and/or relatives presenting at the centre will be informed about the study, and will be invited to provide consent at the time of admission inside the treatment centre. Only patients for whom ebola infection is confirmed with polymerase chain reaction (PCR) will be enrolled in the study. After inclusion, eligibility to the intervention will be reassessed on regular intervals. If the eligibility criteria are not met by 48 hours after inclusion, only SC will be continued.
In line with the guidance of the World Health Organization (WHO), two units of CP will be given. EVD patients will be transfused with ABO-compatible CP using standard procedures. Details on the modalities of transfusion can be found in the WHO guidance document and the MSF guidelines on blood transfusion. All patients will be under close observation for transfusion-related adverse reactions during and up to 4 hours after transfusion. 24 hours after the start of transfusion, a blood sample will be collected for viral load assessment. All other aspects of patient management will be according to MSF clinical guidelines. The decision to discharge a patient should be taken on clinical grounds, but can be supported by the laboratory results. After discharge, the patient will be followed up by the study team until day 30.
详细描述
West-Africa is being ravaged by the worst outbreak of Ebola Viral Disease (EVD) ever witnessed. Nine months after its onset, the outbreak has spiraled and currently appears to be out of control. One of the key factors contributing to the high mortality is the lack of any proven effective EVD specific treatment. The identification of effective therapies is a medical and public health priority. Convalescent whole blood (CWB) and convalescent plasma (CP) have been prioritized by the World Health Organization (WHO) to be evaluated within a short time span, so that widespread use for therapy could be implemented rapidly if proven effective. Both CWB and CP contain EBV antibodies and either could potentially be of value as EVD therapy, however their efficacy in Ebola must still be demonstrated. .
This is an emergency, phase 2/3, open-label, non-randomized, clinical trial that will evaluate CP added to standardized supportive care (SC) in patients with confirmed EVD. No patient will be refused CP when compatible products are available and all efforts will be made to maximize CP availability during the study. EVD patients recruited during the period before CP becomes available or for whom no compatible CP is available will be given SC and will be followed for study outcomes. Data from these SC patients will be the used as comparator in the analysis of the study.
The primary objective of the study is to assess if CP + SC improves the 14 day survival of patients, compared to SC alone. Secondary objectives are;
- to assess 30 day survival on CP + SC
- to assess the relationship between EV antibody levels in donated CP and survival in patients receiving CP
- to assess the relationship between EV antibody levels in donated CP and changes in levels of viral RNA in the blood of patients receiving CP
- to assess the occurrence of serious adverse reactions (SARs) related to CP transfusion in Ebola patients
- to assess the occurrence of safety risks related to CP transfusion in health workers administering the treatments
- to determine risk factors for mortality despite administration of CP (for identification of patients most likely to benefit)
The Investigators aim to enroll a total number of 130 - 200 patients treated with CP assuming equal numbers of patients treated with SC alone. The number of patients treated with SC will be determined by the time interval for CP to become available for treatment and the availability of CP throughout the study. If there would be insufficient patients treated with SC, patients treated at the research site prior to study start may be included in the comparison group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PCR-confirmed, symptomatic infection with Ebola virus
- •Patient's, guardian's or representatives' willingness to provide written informed consent
排除标准
- •A patient is not eligible to receive CP if they meet one of the following criteria:
- •History of allergic reaction to blood or plasma products (as judged by the investigator or treating physician);
- •Medical conditions in which receipt of additional fluid related to the transfusion (250-500 ml or in the case of children 10 ml/kg) may be detrimental to the patient (e.g. decompensated congestive heart failure or renal failure).
- •Patients in shock unresponsive to fluid challenge
- •Patients in shock with signs of multi-organ failure, defined as oliguria/anuria AND impaired consciousness AND/OR jaundice
- •Condition of patient where the procedure of plasma administration carries a risk for the staff
研究组 & 干预措施
Convalescent Plasma
Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg
干预措施: Convalescent Plasma (Other)
standard care
The control arm will consist of historical controls having being treated with standard of care
结局指标
主要结局
Survival at Day 14 After Start of Intervention
时间窗: 14 days
Effect of convalescent plasma in improving patients survival at day 14; it will be considered clinically significant if there is an absolute decrease in the case fatality rate of 20% or more, compared to SC alone
次要结局
- Mortality Risk Factor: Ct(30 days)
- Number of Transfusion-related Serious Adverse Reactions (SARs)(30 days)
- Number of Participants Who Died Corresponding to EV Antibody Levels (Anti-EBOV IgG)(14 days)
- Number of Professional Safety Incidents(9 months)
- Number of Participants Who Died Corresponding to EV Antibody Levels (Neutralizing Antibodies)(14 days)
- Mortality Risk Factor: Age(30 days)
- Number of Participants With 30 Days Survival(30 days)
- Titer of Ebola Viral RNA(30 days)