An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 593
- 试验地点
- 39
- 主要终点
- Ordinal Outcome Scale - Day 7
研究概览
简要总结
This protocol will serve as a platform for assessing treatments for adult patients hospitalized for medical management of COVID-19 without related serious end-organ failure. Trials will involve sites around the world strategically chosen to ensure rapid enrollment. This trial will compare hyperimmune intravenous immunoglobulin (hIVIG) with matched placebo, when added to standard of care (SOC), for preventing further disease progression and mortality related to COVID-19. SOC will include remdesivir unless it is contraindicated for an individual patient.
详细描述
The primary endpoint of this trial in hospitalized patients is an ordinal outcome based on the patient's clinical status on Day 7. It includes 7 mutually exclusive categories capturing the range of organ dysfunction that may be associated with progression of COVID-19, such as respiratory dysfunction and coagulation-related complications. The ordinal endpoint is defined as follows:
-
Death
-
End-organ failure
-
Life-threatening end-organ dysfunction
-
Serious end-organ dysfunction
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
- •SARS-CoV-2 infection documented by polymerase chain reaction (PCR) or other nucleic acid test (NAT) within 3 days prior to randomization OR documented by NAT more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection
- •Symptomatic COVID-19 disease
- •Duration of symptoms attributable to COVID-19 ≤ 12 days
- •Requiring inpatient hospital medical care for clinical manifestations of COVID-19 (admission for public health or quarantine only is not included)
- •Willingness to abstain from participation in other COVID-19 treatment trials until after study Day 7
- •Provision of informed consent by participant or legally authorized representative
排除标准
- •Prior receipt of SARS-CoV-2 hIVIG or convalescent plasma from a person who recovered from COVID-19 at any time
- •Prior receipt of standard IVIG (not hyperimmune to SARS-CoV-2) within 45 days
- •Current or predicted imminent (within 24 hours) requirement for any of the following:
- •Invasive ventilation
- •Non-invasive ventilation
- •Extracorporeal membrane oxygenation
- •Mechanical circulatory support
- •Continuous vasopressor therapy
- •History of allergy to IVIG or plasma products
- •History of selective IgA deficiency with documented presence of anti-IgA antibodies
- •Any medical conditions for which receipt of the required volume of intravenous fluid may be dangerous to the patient (includes New York Association Class III or IV stage heart failure)
- •Any of the following thrombotic or procoagulant disorders:
- •Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomization
- •History of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome
- •Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments
研究组 & 干预措施
Control Group
Participants in this group will receive a placebo and standard of care (SOC).
干预措施: Placebo (Other)
Intervention Group
Participants in this group will receive the investigational product and standard of care (SOC).
干预措施: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) (Biological)
Intervention Group
Participants in this group will receive the investigational product and standard of care (SOC).
干预措施: Remdesivir (Drug)
Control Group
Participants in this group will receive a placebo and standard of care (SOC).
干预措施: Remdesivir (Drug)
结局指标
主要结局
Ordinal Outcome Scale - Day 7
时间窗: 7 days
The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19 Outcome is reported as the percent of participants in each of 7 categories. Primary ordinal outcome based on the patient's clinical status on Day 7. It includes 7 mutually exclusive categories capturing the range of organ dysfunction that may be associated with progression of COVID-19, such as respiratory dysfunction and coagulation-related complications. Minimum value = 1, Maximum value = 7 Higher scores mean a worse outcome
Primary Safety Outcome - Death, SAE or Grade 3 or 4 Events Through Day 7
时间窗: Through Day 7
Number of participants with death, SAE or Grade 3 or 4 event through Day 7
次要结局
- N Reaching 2 Most Favorable Categories(All of follow-up (through Day 28))
- N Discharged or in Most Favorable Category(All of follow-up (through Day 28))
- N Reaching 3 Least Favorable Categories(All of follow-up (through Day 28))