Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19

NCT05271929 | Terminated Phase 3 DMC

• 1 other identifier: COVIC-19
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 14

Brief Summary

• 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)

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Proportion of participants with hospitalisation for progressive COVID-19 symptoms or death

  Day 14

• 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

• 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

Other Outcomes (5)

• Change in SARS-CoV-2 RNA level

  Day 3, 14, 28, 180

• Change in anti-SARS-CoV-2 spike antibody levels in blood

  Day 14, 28

• SARS-CoV-2 whole-genome sequence analysis

  Day 1, 28

Study Arms (2)

Current standard of care

ACTIVE COMPARATOR

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.

Other: Current standard of care

Current standard of care and convalescent plasma

EXPERIMENTAL

Current standard of care and the infusion of two plasma units collected from two different COVID-19 convalescent patients.

Biological: Current standard of care and COVID-19 convalescent and vaccinated plasma

Interventions

Current standard of care and COVID-19 convalescent and vaccinated plasma BIOLOGICAL

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 and convalescent plasma

Current standard of care OTHER

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen: lead
• NHS Blood and Transplant: collaborator
• Erasmus Medical Center: collaborator

Study Sites (14)

CHU Besançon

Besançon, 25000, France

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, Baden-Wurttemberg, 73527, Germany

Location

Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, 70174, Germany

Location

Diakonie-Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, 70176, Germany

Location

Uniklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Institut für Klinische Transfusionsmedizin (IKT)

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Uniklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitätsklinikum Brandenburg

Brandenburg, Brandenburg, 14770, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Elblandkliniken Riesa

Riesa, Saxony, 01589, Germany

Location

Charité Medizinische Klinik IV

Berlin, 10117, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

Erasmus Medical Center

Rotterdam, 3000CA, Netherlands

Location

NHS Blood and Transplant

Oxford, United Kingdom

Location

Related Publications (3)

• 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 Oct;65(10):1888-1902. doi: 10.1111/trf.18394. Epub 2025 Sep 12.

  PMID: 40937925 DERIVED

• 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.

  PMID: 40020259 DERIVED

• 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.

  PMID: 37105693 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Pierre Tiberghien, MD, PhD

  Etablissement Français du Sang, La Plaine Saint-Denis, France

  STUDY DIRECTOR

• Eric Toussirot, MD, PhD

  Rheumatology department, CHU Besançon, France

  PRINCIPAL INVESTIGATOR

• Hubert Schrezenmeier, MD, PhD

  German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen

  PRINCIPAL INVESTIGATOR

• Lise Estcourt, MD, PhD

  NHS Blood and Transplant, Oxford, United Kingdom

  PRINCIPAL INVESTIGATOR

• David Roberts, MD, PhD

  NHS Blood and Transplant, Oxford, United Kingdom

  PRINCIPAL INVESTIGATOR

• Bart Rijnders, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 9, 2022
• Study Start: April 1, 2022
• Primary Completion: January 18, 2024
• Study Completion: June 17, 2024
• Last Updated: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); FR (1); DE (11); NL (1)