A Randomized Open Label Phase-II Clinical Trial With or Without Infusion of Plasma From Subjects After Convalescence of SARS-CoV-2 Infection in High-Risk Patients With Confirmed Severe SARS-CoV-2 Disease
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 174
- 试验地点
- 32
- 主要终点
- Clinical Improvement
研究概览
简要总结
The study RECOVER is a randomized, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent/vaccine-boosted plasma or standard of care.
详细描述
The aim of this randomized phase-II study is to gain evidence on the effect of convalescent plasma/vaccine-boosted plasma in the treatment of SARS-CoV-2 infection in high-risk patients.
High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorized in 4 groups:
- group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less.
- group 2, chronic immunosuppression not meeting the criteria of group 1
- group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1μg/mL
- group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2
The duration of the trial for each patient is expected to be about 3 months, including two days of intervention (infusion of CP/PVP), followed by a follow-up of 3 months. Furthermore viral load is measured in nasopharagyngeal swabs at day 1, 3, 5, 10, 14, 28 or until hospital discharge within 84 days after randomization. Treatment response is assessed daily until day 28, thereafter weekly until day 56, and finally at day 84.
Patients randomized into the standard arm of the study have the possibility to cross over into the experimental arm of the study starting at day 10 (+ 2 days) in case of not improving or worsening clinical condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
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
- •PCR confirmed SARS-CoV-2 infection in a respiratory tract sample.
- •Oxygen saturation (SaO2) of 94% or less while breathing ambient air or a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 300 mm Hg.
- •High risk due to either pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less (group 1) and/or chronic immunosuppression not meeting the criteria of group 1 (group 2) and/or Age ≥ 50 -75 years meeting neither the criteria of group 1 nor group 2 (group 3) and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1μg/mL and/or Age ≥ 75 years meeting neither the criteria of group 1 nor group 2 (group 4).
- •Blood hemoglobin concentration ≥ 8 g/dl.
- •Provision of written informed consent.
- •Patient is able to understand and comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations.
- •Male or female patient aged ≥ 18 years
- •Postmenopausal or evidence of non-childbearing status. For women of childbearing potential: negative urine or serum pregnancy test within 14 days prior to study treatment.
排除标准
- •Dementia, psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principle investigator, would affect subject safety and/or compliance.
- •Contraindication to transfusion or history of prior reactions to transfusion blood products.
- •Patients with selective IgA deficiency.
- •Patients with mechanical ventilation and/or extracoporal membrane oxygenation (ECMO) at time of initial inclusion into the trial. Mechanical ventilation is defined as either NIV - non-invasive ventilation or positive pressure ventilation. Enrollment into another clinical trial evaluating specific therapies for COVID-19 is encouraged.
- •Participation in another trial with an investigational medicinal product.
- •Treatment with SARS-CoV-2 convalescent/vaccine-boosted plasma in the past.
结局指标
主要结局
Clinical Improvement
时间窗: within 84 days
Time from randomization until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital
次要结局
- Overall survival rate(within 84 days)
- Cytokine profiles(within 84 days)
- Viral clearance(within 84 days)
- Discharge from hospital(within 84 days)
- Antibody titres(within 84 days)
- Requirement of mechanical ventilation(within 84 days)
研究者
Carsten Müller-Tidow
Medical Director
University Hospital Heidelberg