A Randomised Open-Label Trial of Early, Very High-Titre Convalescent Plasma Therapy in Clinically Vulnerable Individuals With Mild COVID-19
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 120
- 试验地点
- 14
- 主要终点
- Proportion of participants with hospitalisation with progressive COVID-19 symptoms or death
研究概览
简要总结
- Research Question: Does convalescent plasma (CCP) collected from donors who have recovered from COVID-19 and who have a very high titre of anti-SARS-CoV-2 antibodies reduce the risk of hospitalisation (for COVID-19) or death in patients with early symptoms of acute COVID-19 who are vulnerable to this disease compared to standard of care?
- Study product: Very high antibody titre COVID-19 convalescent plasma collected more than 15 days after end of symptoms in COVID-19 patients who also had received at least one dose of a SARS-CoV-2 vaccine.
- Methodology: Multicentre, randomised, open-label, adaptive superiority trial: COVID-19 very high neutralizing Ab titre convalescent plasma vs standard care in 2 cohorts of vulnerable patients (cohort 1: elderly (≥ 70 years) and younger with comorbidities, cohort 2: immunosuppressed patients).
- Study phase: Phase 3
- Intervention: Two units of high antibody titre COVID-19 convalescent plasma to individuals randomised to the intervention group, 2 units from 2 different donors, preferably transfused on the same day. Plasma provided by convalescent vaccinated donors with a minimum antibody titre of 1:640 against delta variant (B1.617.2) or antibody concentration >=4.000 BAU/ml in the QuantiVac anti-SARS-CoV-2 IgG ELISA or >=20.000 U/ml in the Elecsys anti-SARS-CoV-2 CLIA
- Randomisation: 1:1 (standard of care + convalescent plasma vs. standard of care) stratified by centre (cohorts 1 and 2)
详细描述
COVIC-19 is a multicentre international, randomised, open-label adaptive superiority phase III trial to evaluate the efficacy and safety of COVID-19 convalescent plasma in the treatment of COVID-19. It is conducted in a harmonized approach in different countries in Europe.
The study is randomizing adult COVID-19 patients to one of two arms (1:1 ratio): standard of care or standard of care and very high neutralizing Ab titre convalescent plasma. Randomization will be stratified by centre and by patient cohort. The control group will receive 'standard care' therapy. Neither blinding nor placebo will be used to avoid unnecessary intravenous access.
Standard of care therapy may include anti-SARS-CoV-2 specific medication listed as authorized in the protocol. Centres should ensure that medications used as standard of care are used similarly for patients in both treatment arms.
Participating patients will be included in 2 cohorts of vulnerable patients (cohort 1: elderly (≥ 70 years) and younger with comorbidities (cohort 1: < 70 with comorbidities), cohort 2: immunosuppressed patients).
All subjects will undergo a series of efficacy and safety assessments, including laboratory assays. Subjects will be assessed at baseline, and at Days 3, 14, 28, 90 and 180.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Age < 18 years (France and Germany only)
- •Prior or concurrent treatment for COVID-19 (unless listed as authorized)
- •History of COVID-19 disease in the last 90 days prior to enrollment
- •Prior anti-SARS-CoV-2 immunization
- •Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components
- •Known participant objection to receiving plasma products
- •Primary or acquired immune deficiency listed below (see cohort 2)
- •Refusal to participate expressed by patient or legally authorised representative
- •Pregnancy
- •Cohort 2: High-risk immunocompromised population
- •Inclusion criteria:
- •SARS-CoV-2 RNA, or positive antigenic test, detected in a specimen, ≤ 7 days after onset of symptoms
- •Symptoms of COVID-19 (so including but not limited to: fever; cough; breathlessness; chest pain; wheeze; sore throat; haemoptysis; runny nose; fatigue; muscle or joint pain; confusion; headache; seizures; nausea; vomiting; diarrhoea; abdominal pain; poor appetite; skin ulcers or rash; ear pain; conjunctivitis; anosmia; bleeding; lymphadenopathy. The attending clinician will determine if symptoms are consistent with COVID-
- •Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support
- •Ability to transfuse (per randomisation) within 7 days after onset of symptoms
- •Male or female with extremely high risk including:
- •a. Patients with at least one of the following acquired immune deficiencies
- •i. Lymphoid malignancies treated within the last 12 months ii. Lymphoid malignancies with persistent hypogammaglobulinaemia (IgG < 5g/L) iii. Myeloid malignancies treated by chemotherapy within the last 12 months iv. Myeloid malignancies treated by anti-BCL-2 drugs within the last 12 months v. Myeloid malignancies associated with prolonged neutropenia (≥ 6 weeks) vi. Solid tumour undergoing treatment with chemotherapy (until 3 months after completion of the last chemotherapy cycle) vii. Allogenic hematopoietic stem cell transplantation within the last 12 months or anytime if on-going treatment for chronic GVHD viii. Organ transplantation ix. Anti-B (CD20/CD19) MoAb and/or mycophenolate mofetil treatment within the last 12 months x. Anti-CD19/CD20 CAR-T cell treatment xi. ATG or alemtuzumab treatment within the last 6 months xii. AIDS
- •OR b. Patients with primary lymphoid immune deficiencies. i. B cell deficiencies (such as Bruton agammaglobulinemia) ii. T cell deficiencies (such as Wiskott Aldrich disease) iii. Combined deficiencies (such as Common variable immunodeficiency).
- •OR c. Patients without detectable seroconversion ≥ 3 weeks after complete vaccination schedule with an approved vaccine.
- •Exclusion Criteria:
- •Age < 18 years (France and Germany only)
- •Prior or concurrent treatment for COVID-19 (dexamethasone, anti-IL-6/IL6R, remdesivir) except for prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies (pre or post exposure) and authorized specific treatment
- •History of COVID-19 disease in the last 90 days prior to enrollment
- •Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components
- •Known participant objection to receiving plasma products
- •Refusal to participate expressed by patient or legally authorised representative
- •Pregnancy
研究组 & 干预措施
Current standard of care
Standard of care therapy may include anti-SARS-CoV-2 specific medication such as, but not limited to:
- Casirivimab
- Casirivimab / Imdevimab (REGN-COV2 or Ronapreve)
- Imdevimab
- Sotrovimab (Xevudy)
- Tixagevimab / Cilgavimab (Evusheld)
- Molnupiravir (MK-4482)
- Nirmatrevlir / Ritonavir (Paxlovid)
- Remdesivir
Centres should ensure that medications used as standard of care are used similarly for patients in both treatment arms.
干预措施: Current standard of care (Other)
Current standard of care and convalescent plasma
Current standard of care and the infusion of two plasma units collected from two different COVID-19 convalescent patients.
干预措施: Current standard of care and COVID-19 convalescent and vaccinated plasma (Biological)
结局指标
主要结局
Proportion of participants with hospitalisation with progressive COVID-19 symptoms or death
时间窗: Day 28
Proportion of participants with (1) at least one overnight stay in hospital for progressive COVID-19 symptoms or (2) who died
次要结局
- All-cause mortality(Day 28, 90, 180)
- Proportion of patients with supplemental oxygen(Day 14, 28)
- Proportion of patients with non-invasive ventilation(Day 14, 28)
- Proportion of patients with hospitalisation for progressive COVID-19 symptoms requiring O2 support*, or death *O2 support: requirement based on O2 saturation level on room air <=93% or respiration rate >30(Day 14 and Day 28)
- Proportion of patients with admission to ITU(Day 14, 28)
- Proportion of patients with long COVID-19 symptoms and time to recovery(Day 28, 180)
- Change in 10-point WHO Clinical Progression Scale score(Day 14, 28)
- Duration of ITU admission censored at 28 days(Day 28)
- Health-related quality of life assessed by EQ-5D quality of life index(Day 28, 180)
- Duration of hospital admission censored at 28 days(Day 28)
- Proportion of participants with hospitalisation for progressive COVID-19 symptoms or death(Day 14)
- Proportion of patients with intubation and mechanical ventilation(Day 14, 28)
- Number of Serious Adverse Events(72 hours)
- Number of Participants with arterial and venous thromboembolic events(Day 28, 90, 180)