Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Clinical Improvement within 28 days of randomization
研究概览
简要总结
The expanded access program for investigational convalescent plasma (CP) is being utilized nationwide despite its unproven benefit and optimal timing of transfusion. The optimal administration of CP during a viral pandemic must consider the supply of the product, ideal patient selection, and appropriate timing in order to produce maximum benefit with a scarce resource [2]. Currently, the FDA suggested guidelines for use include "severe", "critical" or at risk for critical disease. The optimal administration of CP with anti-SARS-CoV-2 antibodies is theoretically early in the course of the illness [1], before multiorgan failure or a maladaptive immune response, like seen in the cytokine release syndrome, occurs. Our open-label trial will randomize COVID-19+ patients admitted to the hospital who are at high risk for severe disease to receive 1 dose CP ordered within 48 hours of admission plus standard of care vs. standard of care. The primary clinical endpoint will be time to clinical improvement within 28 days after randomization (based on the ordinal scale as specified below). The purpose of this trial will be to obtain data which can be further utilized in future clinical trials and help clinicians understand the effectiveness of CP.
详细描述
Based on previous veterinary and human studies of coronavirus vaccines, it is probable that an effective vaccine is 1-2 years away. Multiple antiviral medications are being currently studied, but manufacturing capacity of adequate quantities may be 6-12 months away from the identification of an effective drug. In addition, effective drugs or a vaccine may not be available to all countries given current international shortages. Conversely, blood banks have a well established infrastructure for the collection and distribution of convalescent plasma. If convalescent plasma is effective in the treatment of COVID-19, it would be accessible much more quickly, and would likely be available in all geopolitical regions and all economic strata. Therefore, it is imperative to study all possible approaches to the use of convalescent plasma. Based on other antiviral therapies, and previous experience with convalescent plasma, we believe it is very likely that early use of plasma will be more likely to be effective as therapy in COVID-19. Our study is designed to explore the possibility that early use is beneficial.
Convalescent plasma has been used successfully in previous viral outbreaks, including 1918 influenza pandemic, MERS, previous SARS, Ebola virus and others. The goal of this study is to provide rapid data the medical community can use to evaluate its effectiveness in the current pandemic.
The current FDA emergency authorization for CP allows for its use in severe, critical or at risk for critical disease as defined by the FDAs suggested guidelines for use. It has been documented that some of the mortality and morbidity associated with COVID-19 is related to the cytokine release syndrome due to an overactivated immune response. The theoretical optimal time for convalescent plasma infusion is early in the course, when viremia peaks and the primary immune response has yet to adequately suppress the viral illness [1]. Scarce resources during pandemics should be utilized to achieve maximum benefit [2]. We are proposing a study which aims to document early intervention in a high risk group. Once this information is available, and if it is found to be effective, we believe COVID-19 recovered patients will be easier to recruit into other "from community to community" plasma donation systems such as ours.
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After informed consent is obtained, the enrolling physician will be required to present the case to the principal investigator to ensure they meet inclusion criteria. The trial sponsor Larkin Community Hospital has published internal protocols pertaining to the recommended laboratory monitoring for COVID-19 patients which should be followed by all physicians enrolling patients in the trial; these guidelines include: D-dimer, C-reactive protein, lactate dehydrogenase, and ferritin level (at admission and every 48 hours), complete blood count and comprehrensive metabolic panel (at admission and daily); and electrocardiogram and chest x-ray (at admission and with changes in clinical status). Arterial blood gas will be ordered for any Intensive Care admission or at attending physician's discretion.
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After obtaining patient consent, patients will be assigned a study ID which will correlate to the patient's medical record. The list with patient identifiers will be held only by the investigative team. The ordering physician will not know to which group the patient will be assigned until after enrollment. Patients will be stratified by age at time of enrollment (40-64 years old, 65-79 years, 80+ years). The stratified patients will then be randomized using variable block sizes using an electronically generated randomization scheme (e.g. www.randomization.com) to either the convalescent plasma treatment group or standard care.
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Patients in the treatment arm will receive 1 unit (minimum 200mL) of ABO compatible convalescent plasma one time. ABO compatible convalescent plasma units will be obtained from a registered or licensed blood collector following registration of the patient.
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
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Admitted to the participating acute care facilities as listed above (Larkin Palm Springs Hospital, Larkin South Miami Hospital) AND enrolled in the trial within 48 hours of hospital admission (defined by when admission order was placed) AND
- •Age ≥ 40 with at least one of the following comorbidities (hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, pulmonary hypertension, idiopathic pulmonary fibrosis, asthma, COPD, cancer, HIV/AIDS, chronic kidney disease, immunosuppression, obesity). OR
- •Age ≥ 65 years of age with or without comorbid conditions. AND
- •Severe or life-threatening COVID-19 disease as defined by the FDA:
- •"Severe disease is defined as one or more of the following: shortness of breath (dyspnea), respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, lung infiltrates > 50% within 24 to 48 hours, Life-threatening disease is defined as one or more of the following: respiratory failure, septic shock, multiple organ dysfunction or failure AND
- •Positive COVID-19 test via nasopharyngeal or pharyngeal PCR.
- •Able to consent to treatment
排除标准
- •Unable to consent
- •Lack of laboratory confirmed COVID-19 infection.
- •Hospice/Palliative care
- •Unable to tolerate 200mL of fluid.
- •History of IgA deficiency (due to risk of reaction)
- •History of anaphylactoid or other severe reaction to plasma or blood products.
- •Philosophical/Religious objections to receiving blood products.
- •Pregnant or breastfeeding
研究组 & 干预措施
Convalescent Plasma
干预措施: Convalescent Plasma (Drug)
Standard of care
干预措施: Standard of Care (Other)
结局指标
主要结局
Clinical Improvement within 28 days of randomization
时间窗: 7, 14 and 28 days after randomization
Clinical improvement will be defined as a two-point reduction in patients' admission status on a 6-point ordinal scale, or discharge from the hospital, whichever comes first. The 6-point scale is as follows: Discharged = 0 Not requiring supplemental oxygen =1 Requiring supplemental oxygen =2 Requiring noninvasive mechanical ventilation =3 Requiring invasive mechanical ventilation = 4 Death = 5
次要结局
- Mortality at day 28; frequency of invasive mechanical ventilation; duration of oxygen therapy; duration of hospital admission(Within 28 days)