VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 75
- 试验地点
- 24
- 主要终点
- Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death
研究概览
简要总结
The purpose of this study is to determine if treatment with convalescent plasma improves the clinical outcomes of Veterans who are hospitalized and require supplemental oxygen due to COVID-19.
详细描述
As of August 25, 2020, SARS-Coronavirus 2 (SARS-CoV-2; COVID-19) infections are approaching 6 million persons and 180,000 deaths in the US. Of the 20% of patients admitted to hospital, up to half progress to ICU admission, respiratory failure or death. Prominent among these progressors are older men, particularly those with underlying comorbidities (e.g., hypertension, diabetes, lung, heart, kidney or liver disease, obesity and immunocompromised), all common among Veterans. There are no drugs or other therapeutics approved by the FDA to prevent or treat COVID-19 infection.
Convalescent plasma therapy is being used empirically, although only five of six small uncontrolled case series (total n=56) in SARS-CoV-23-8 and a recent study with non-randomized controls suggest improved selected clinical, virologic and laboratory outcomes; outcomes in another small randomized trial were equivocal. For other infections, such as influenza and Ebola virus, promising observational studies were not reliably confirmed by controlled trials. In multiple infections, use of convalescent plasma has been distinguished by its safety profile but not by the consistency of its benefit.
The current double-blind, placebo-controlled randomized clinical trial (RCT) is designed to determine definitively whether this intervention is effective in a population at high risk of complications and death from SARS-CoV-2 infection. The investigators compare the effect of convalescent plasma vs. saline placebo with a robust study design, adequate sample size and statistical and logistical rigor to assure that the interventions the investigators make to treat serious disease are well-validated to support its use or to move on to test other potentially safe and effective treatments.
This study is taking place at approximately 25 Veterans Affairs (VA) Medical Centers located across the US. A participant's involvement will last up to 33 days. The entire study, from the date the first person enters until the last participant is seen, is expected to last about 20 months.
Data collected for this study will be analyzed and stored at the Palo Alto Cooperative Studies Program Coordinating Center (CSPCC). After the study is completed, the de-identified, archived data will continue to be stored at the Palo Alto CSPCC, accessible for use by researchers including those outside of the study with an approved Data Use Agreement. The biospecimens collected in the study for current and future research will be kept at the VA Biorepository in Palo Alto, California unless otherwise specified. The biospecimens will be accessible for future research with an approved Sample Use Agreement. The VA Central Institutional Review Board (CIRB) will oversee the biorepository for this study. All samples will be destroyed by standard practice within 20 years of study completion. Sample destruction will be validated according to the Standard Operating Procedures of the VA Biorepository.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
The participants, site investigators, clinical prescribers, site coordinators, and most other individuals involved in this study will be blinded to the treatment assignment.
Furthermore, the blind will not routinely be broken in order to select post-study, pharmacologic treatment for SARS-CoV-2 infection administered by clinical healthcare providers.
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
- •Veterans must meet all of the following criteria to be eligible to participate:
- •Admitted to a participating VA clinical site with symptoms suggestive of SARS-CoV-2 infection.
- •Participant (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
- •Participant (or legally authorized representative) understands and agrees to comply with planned study procedures.
- •Veteran 18 years of age at time of screening.
- •Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or antigen test, as documented by either of the following:
- •(1)Reverse Transcription polymerase chain reaction (RT-PCR) or antigen positive (nasopharyngeal, oropharyngeal, saliva, lower respiratory) in sample collected 72 hours prior to screening; (2)RT-PCR or antigen positive in sample collected > 72 hours but 168 hours (i.e. 7 days) prior to screening, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc.), AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
- •6.Requiring oxygen by nasal cannula or by face-mask as a new treatment (or if previously on home oxygen, at a liter flow at least 2 Lpm greater than home prescription), but not on humidified heated high-flow nasal cannula (HHHFNC) at 15 Lpm.
- •7.Can be randomized within 72 hours of hospital admission. 8.Agrees not to participate in another therapeutic clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29 without approval from the investigator(s). Taking part in other research studies, including those unrelated to SARS-CoV-2, without first discussing it with the investigators of this study may invalidate the results of this study, as well as that of the other study.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Respiratory failure requiring mechanical ventilation, non-invasive ventilation including continuous positive airway pressure (CPAP) (for an indication other than previously diagnosed sleep apnea and maintained on outpatient settings), or extra-corporeal membrane oxygenation or anticipated to require any of those treatments or to die within 24 hours.
- •Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 hours.
- •History of previous transfusion reaction.
- •Previously documented serum immunoglobulin A (IgA) deficiency (<7 mg/dL)
- •Documented to have received convalescent plasma in the last 60 days.
研究组 & 干预措施
Convalescent Plasma
The study intervention consists of intravenous administration of 200-500 mL of convalescent plasma administered in two equally divided doses, less than 12 hours apart.
干预措施: Convalescent Plasma (Drug)
Masked Saline Placebo
The study intervention consists of intravenous administration of 200-500 mL of 0.9% saline administered in two equally divided doses, less than 12 hours apart.
干预措施: Masked Saline Placebo (Other)
结局指标
主要结局
Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death
时间窗: Day 1 through Day 28
Respiratory failure is defined as requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.
次要结局
- Proportion of Patients Who Died From Any Cause, Had Respiratory Failure, or Required Humidified Heated High-flow Nasal Cannula (HHHFNC) at >= 15 Lpm(Day 1 through Day 28)
- Time (in Days) to Death, Respiratory Failure, or HHHFNC at >= 15 Lpm(Day 1 through Day 28)
- Time to an Improvement of at Least Two Categories Using an Ordinal Scale(Up through 28 days.)
- Time to Discharge or to a National Early Warning Score 2 (NEWS2) of <= 2 Maintained for at Least 22 Hours, Whichever Occurs First(Up through 28 days.)
- Number of Participants With 28-day All-cause Mortality(Day 1 through Day 28)
- Categorical Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28(From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.)
- Incidence of Discontinuation or Temporary Suspension of Study Product Administrations (for Any Reason)(Day 1 through Day 3)
- Time (in Days) to Death or Respiratory Failure(Day 1 through Day 28)
- Time to an Improvement of at Least One Category Using an Ordinal Scale(Up through 28 days.)
- Change in National Early Warning Score 2 (NEWS2) From Day 1 (Baseline) to Days 2, 4, 7, 11, 15, and 29(From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29)
- Time (in Days) to Recovery(Day 1 through Day 28)
- Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28(From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.)
- Duration of Hospitalization(Day 1 through Day 28)
- Participant's Clinical Status by Ordinal Scale(Days 2, 4, 7, 11, 14, 21, and 28)