COVID-19 Clinical Trial
— COVIC-19Official title:
A Randomised Open-Label Trial of Early, Very High-Titre Convalescent Plasma Therapy in Clinically Vulnerable Individuals With Mild COVID-19
- 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)
Status | Recruiting |
Enrollment | 680 |
Est. completion date | September 10, 2024 |
Est. primary completion date | March 10, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility | Cohort 1: Elderly and high COVID-age population: Inclusion criteria: - SARS-CoV-2 RNA 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-19. - 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 - Men or women, 70 years or older OR - under 70 years with significant comorbidities (arterial hypertension, diabetes, obesity, asthma or other chronic pulmonary disease, cardiovascular disease, cerebrovascular disease, chronic kidney disease / dialysis, hemoglobinopathies, liver disease, chronic neurological disease, rheumatoid arthritis, lupus or psoriasis) resulting in a 'COVID-age' of 70 years or more according to the ALAMA risk calculator https://alama.org.uk/covid-19-medical-risk-assessment/ Exclusion Criteria: - 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 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-19. - 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 |
Country | Name | City | State |
---|---|---|---|
France | CHU Besançon | Besançon | |
Germany | Charité Medizinische Klinik IV | Berlin | |
Germany | Universitätsklinikum Brandenburg | Brandenburg an der Havel | Brandenburg |
Germany | Klinikum Chemnitz gGmbH | Chemnitz | |
Germany | Universitätsklinikum Frankfurt | Frankfurt | Hessen |
Germany | Stauferklinikum Schwäbisch Gmünd | Mutlangen | Baden-Wuerttemberg |
Germany | Elblandkliniken Riesa | Riesa | Sachsen |
Germany | Diakonie-Klinikum Stuttgart | Stuttgart | Baden-Wuerttemberg |
Germany | Klinikum Stuttgart | Stuttgart | Baden-Wuerttemberg |
Germany | Uniklinikum Tübingen | Tübingen | Baden-Wuerttemberg |
Germany | Institut für Klinische Transfusionsmedizin (IKT) | Ulm | Baden-Wuerttemberg |
Germany | Uniklinikum Ulm | Ulm | Baden-Wuerttemberg |
Netherlands | Erasmus Medical Center | Rotterdam | |
United Kingdom | NHS Blood and Transplant | Oxford |
Lead Sponsor | Collaborator |
---|---|
Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen | NHS Blood and Transplant |
France, Germany, Netherlands, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Change in SARS-CoV-2 RNA level | Polymerase chain reaction, Cycle Threshold value in oral or nose/throat swab samples at days 3, 14, 28 and 180 after randomisation | Day 3, 14, 28, 180 | |
Other | Change in anti-SARS-CoV-2 spike antibody levels in blood | Day 14, 28 | ||
Other | SARS-CoV-2 whole-genome sequence analysis | Day 1, 28 | ||
Other | Proportion and clinical characteristics of patients with cultivable virus | Day 28, 180 | ||
Other | Virus sequence variation and cultivability over time, overall and in individuals receiving vs not receiving CCP | Day 1, 28 | ||
Primary | Proportion of participants with hospitalisation with progressive COVID-19 symptoms or death | Proportion of participants with (1) at least one overnight stay in hospital for progressive COVID-19 symptoms or (2) who died | Day 28 | |
Secondary | Proportion of participants with hospitalisation for progressive COVID-19 symptoms or death | Day 14 | ||
Secondary | 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 | ||
Secondary | All-cause mortality | Day 28, 90, 180 | ||
Secondary | Proportion of patients with supplemental oxygen | Day 14, 28 | ||
Secondary | Proportion of patients with non-invasive ventilation | Day 14, 28 | ||
Secondary | Proportion of patients with intubation and mechanical ventilation | Day 14, 28 | ||
Secondary | Change in 10-point WHO Clinical Progression Scale score | The 10-point WHO clinical progression scale ranges from 0 to 10 (0: uninfected; 10: death) | Day 14, 28 | |
Secondary | Duration of hospital admission censored at 28 days | Day 28 | ||
Secondary | Proportion of patients with admission to ITU | Day 14, 28 | ||
Secondary | Duration of ITU admission censored at 28 days | Day 28 | ||
Secondary | Proportion of patients with long COVID-19 symptoms and time to recovery | Day 28, 180 | ||
Secondary | Health-related quality of life assessed by EQ-5D quality of life index | EQ-5D is one of the most widely used Health-related quality of life measure. EQ-5D questionnaires have 5 dimensions: Mobility, Human Autonomy, Current Activities, Pain & Discomfort, "Anxiety & Depression, and all dimensions are described by 5 levels corresponding to patient response choices. A quality of life index ranging from less than 0 (worse than death) to 1 (full health) is derived from the answers to the questionnaires. |
Day 28, 180 | |
Secondary | Number of Serious Adverse Events | Grade 3/4 adverse events and AE unexpected for their nature, onset, evolution, severity or frequency | 72 hours | |
Secondary | Number of Participants with arterial and venous thromboembolic events | Day 28, 90, 180 |
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