Randomized, Double-Blind, Placebo-Controlled Study of Convalescent Plasma in the Treatment of Covid-19
试验速览
- 阶段
- 2 期
- 入组人数
- 390
- 试验地点
- 2
- 主要终点
- Safety (SAE)
研究概览
简要总结
This study investigates the possible adverse effects and effectiveness of convalescent plasma for patients infected with SARS-CoV-2. Following provision of informed consent, patients will be randomized into three groups: High-titre convalescent plasma, low-titre convalescent plasma or placebo. Primary outcomes of the study will cover safety and either intubation or initiation of systemic corticosteroids. Safety information collected will include serious adverse events judged to be related to administration of convalescent plasma. Microbiological and other laboratory parameters will be followed up.
详细描述
SARS-CoV-2 pandemic presents a serious global public health threat urgently requiring both prophylactic and therapeutic interventions. The entry of SARS-CoV-2 into human cells involves a binding between its spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) receptor on human cells. Convalescent sera of Covid-19 patients have been shown to contain SARS-CoV-2-neutralizing antibodies. Accordingly, recovered patients are presumed to be immune to re-infection. Use of convalescent plasma as treatment warrants research, which is supported by the European Commission. Convalescent plasma (CP) therapy is a classical adaptive immunotherapy. It has been applied to prevention and treatment of various infectious diseases: evidence of success has been accumulated e.g. on treatment of SARS, MERS, and 2009 H1N1, for which satisfactory efficacy and safety have been shown.
The investigators will select as donors for CP therapy patients recovered from Covid-19 with a high neutralizing antibody titre who meet normal blood donor eligibility criteria. The donors will be recruited among participants of ongoing Covid-19 immunity studies (Clin-Covid, Commun-Covid) and/or from Finnish Red Cross Blood Service (FRCBS) blood donors.
CP will be prepared from the blood of eligible donors at the FRCBS according to previous protocols and the European guidelines for fresh frozen plasma. After the screening test results required for product release (HCV, HBV, HIV, ABO, Syphilis) are available, the units will be released. All donors will be screened for type-I-Interferon antibodies and women will be screened for HLA-antibodies. The units will be labelled with convalescence plasma labels including ICCBBA/ISBT compliant product codes. The plasma units will be frozen to -25°C within 6 hours from collection. Prior to freezing 3 ml of CP will be separated and divided in 3 aliquots to be stored, for possible later analysis.
Patients admitted to ward at HUH will be randomized 1:1:1 into three groups which will be given 1) high-titre convalescent plasma (HCP), 2) low-titre convalescent plasma (LCP) or 3) placebo. The plasma preparations and placebo will be given as one 200 mL infusion. ABORh blood group will be determined from patients prior to transfusion according to normal transfusion protocols of the hospital. The study will be double-blinded with saline as placebo given to groups three. The primary outcomes of the study will cover safety and intubation/initiation of systemic corticosteroids. AEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo. Thromboembolic and cardiovascular events will be recorded as AEs or SAEs up to 7 days after administration of CP / placebo. SAEs will be reviewed, recorded and reported up to 7 days after administration of CP / placebo. In case of respiratory failures classified as SAEs, the reporting period is only up to 12 hours after administration of CP / placebo.
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
Some of the investigators are masked and some are not
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
- •Acute Covid-19 disease at the time of recruitment laboratory-confirmed by upper respiratory tract PCR
- •Patient recently (0-4 days earlier) admitted to hospital due to Covid-19 infection
- •Symptom onset 10 days before recruitment (if symptom onset unknown the duration is calculated from positive PCR-test)
- •the day should be recorded from the duration of the Covid-19 symptoms/positive test result
- •The dose of LMWH thromboprofylaxis should be recorded
- •Written informed consent.
排除标准
- •Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of IMP; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded ( inhaled or topical steroids allowed)
- •Regular (daily), systemic administration of corticosteroids at the time on inclusion (inhaled or topical corticosteroids are allowed)
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
- •Pregnancy or lactation.
- •Alcohol or drug abuse.
- •Suspected non-compliance.
- •Presence of VTE, including pulmonary embolism or other manifestations of thrombosis
- •Use of any investigational drug (other than hydroxychloroquine) or vaccine within 30 days prior to first dose of study vaccine or planned use during study period.
- •Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction as judged by investigator.
- •Known immunoglobulin A (IgA) deficiency
- •Existing treatment limitations: do-not-resuscitate (DNR) order or withholding treatment in ICU
- •Any other criteria which, as judged by investigator, might compromise a patient's well-being or ability to participate in the study or its outcome.
- •Active malignant disease
- •CP not available for patients blood type
- •Patient cannot assign written consent
- •No personnel available for CP of placebo transfusion
结局指标
主要结局
Safety (SAE)
时间窗: SAEs will be recorded and reported up to 7 days after administration of CP or placebo.
Subsequent serious adverse events (SAE) between active and non-active group
Rate of intubation or systemic corticosteroids initiation
时间窗: 21 days post transfusion
Intubation or systemic corticosteroid treatment (e.g. dexamethasone) started for aggravation of Covid-19
次要结局
- Severity of respiratory failure(21 days post transfusion)
- Viral load(During hospitalizaation, through study completion, up to 1 year)
- Antibody measurements(Through study completion, up to 1 year)
- Hospital stay(Through study completion, up to 1 year)
- Mortality(21 days post transfusion)
- ICU stay(Within 21 days post transfusion)
- The rate of participants presenting with coagulopathy disorders(21 days post transfusion)
- Ventilator days(Within 21 days post transfusion)
- Thrombotic complication(Through study completion, up to 1 year)
- Number of participants with laboratory change(Through study completion, up to 1 year)
- Adverse effects(Through study completion, up to 1 year)
- Convalescent plasma efficacy(21 day post transfusion)
- Convalescent plasma high vs low titer efficacy(21 day post transfusion)
- Convalescent plasma efficacy according to donor status(21 day post transfusion)
研究者
Anu Kantele
Professor
Helsinki University Central Hospital