Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19
NCT ID: NCT05271929
Last Updated: 2024-10-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE3
120 participants
INTERVENTIONAL
2022-04-01
2024-06-17
Brief Summary
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* 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)
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Detailed Description
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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.
Nasopharyngeal swabs (NP) or lower respiratory tract samples will be obtained at D1 (pre-treatment), and at D3, D14 and D28 (and monthly in case of positivity until of clearance) for cohort 2.
Blood samples will be obtained at D1, D14 and D28 and on the day of hospitalization (if applicable).
The trial is sponsored by the University Hospital of Besançon in France, the German Red Cross in Germany and the NHSBT in the United Kingdom.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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.
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.
Current standard of care and COVID-19 convalescent and vaccinated plasma
ABO compatible convalescent plasma infused intravenously on study day 1 (as soon as possible after randomisation) and the second on day 1 or day 2. Plasma obtained by apheresis from donors who have recovered from COVID-19 infection (at least 14 days after recovery) and have been vaccinated (at least 3 weeks after first dose of vaccine). A combination of both a SARS-CoV-infection and a SARS-CoV-2 vaccination of the donor is required - irrespective of the sequence of infection and vaccination. As far as the availability of CCP units allows, the two plasma units should have been donated by two different convalescents.
Interventions
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Current standard of care and COVID-19 convalescent and vaccinated plasma
ABO compatible convalescent plasma infused intravenously on study day 1 (as soon as possible after randomisation) and the second on day 1 or day 2. Plasma obtained by apheresis from donors who have recovered from COVID-19 infection (at least 14 days after recovery) and have been vaccinated (at least 3 weeks after first dose of vaccine). A combination of both a SARS-CoV-infection and a SARS-CoV-2 vaccination of the donor is required - irrespective of the sequence of infection and vaccination. As far as the availability of CCP units allows, the two plasma units should have been donated by two different convalescents.
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.
Eligibility Criteria
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Inclusion Criteria
* 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/
* 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-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
* 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
* 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
ALL
No
Sponsors
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NHS Blood and Transplant
OTHER_GOV
Erasmus Medical Center
OTHER
Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen
OTHER
Responsible Party
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Principal Investigators
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Pierre Tiberghien, MD, PhD
Role: STUDY_DIRECTOR
Etablissement Français du Sang, La Plaine Saint-Denis, France
Eric Toussirot, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Rheumatology department, CHU Besançon, France
Hubert Schrezenmeier, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen
Lise Estcourt, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
NHS Blood and Transplant, Oxford, United Kingdom
David Roberts, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
NHS Blood and Transplant, Oxford, United Kingdom
Bart Rijnders, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Erasmus Medical Center
Locations
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CHU Besançon
Besançon, , France
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Baden-Wurttemberg, Germany
Klinikum Stuttgart
Stuttgart, Baden-Wurttemberg, Germany
Diakonie-Klinikum Stuttgart
Stuttgart, Baden-Wurttemberg, Germany
Uniklinikum Tübingen
Tübingen, Baden-Wurttemberg, Germany
Institut für Klinische Transfusionsmedizin (IKT)
Ulm, Baden-Wurttemberg, Germany
Uniklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
Universitätsklinikum Brandenburg
Brandenburg, Brandenburg, Germany
Universitätsklinikum Frankfurt
Frankfurt am Main, Hesse, Germany
Elblandkliniken Riesa
Riesa, Saxony, Germany
Charité Medizinische Klinik IV
Berlin, , Germany
Klinikum Chemnitz gGmbH
Chemnitz, , Germany
Erasmus Medical Center
Rotterdam, , Netherlands
NHS Blood and Transplant
Oxford, , United Kingdom
Countries
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References
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Hoffmann S, Seidel A, Ludwig C, Vieweg C, Muller R, Hofmann H, Jahrsdorfer B, Wuchter P, Kluter H, Schmidt M, Johnsen M, Burkhardt T, Appl T, Schrezenmeier E, Munch J, Tiberghien P, Schrezenmeier H, Korper S. SARS-CoV-2 convalescent plasma for the controlled clinical trial "COVIC-19": Experience from collection of very high-titer plasma from superimmunized individuals. Transfusion. 2025 Sep 12. doi: 10.1111/trf.18394. Online ahead of print.
Hoffmann S, Schrezenmeier E, Desmarets M, Halleck F, Durrbach A, Peters L, Tremmel AT, Seidel A, Fuhrer M, Bachmann F, Schrezenmeier J, Greiner J, Korper S, Hofmann H, Ludwig C, Vieweg C, Jahrsdorfer B, Budde K, Schmidt M, Munch J, Joher N, Daguindau E, Gruner B, Brunotte G, Vauchy C, Seifried E, Bradshaw D, Estcourt LJ, Roberts DJ, Toussirot E, Rijnders B, Tiberghien P, Schrezenmeier H. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial. EBioMedicine. 2025 Mar;113:105613. doi: 10.1016/j.ebiom.2025.105613. Epub 2025 Feb 27.
Desmarets M, Hoffmann S, Vauchy C, Rijnders BJA, Toussirot E, Durrbach A, Korper S, Schrezenmeier E, van der Schoot CE, Harvala H, Brunotte G, Appl T, Seifried E, Tiberghien P, Bradshaw D, Roberts DJ, Estcourt LJ, Schrezenmeier H. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial. BMJ Open. 2023 Apr 27;13(4):e071277. doi: 10.1136/bmjopen-2022-071277.
Other Identifiers
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COVIC-19
Identifier Type: -
Identifier Source: org_study_id
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