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COVID-19Phase 3COVIC-19NCT05271929

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

A Phase 3 study of COVID-19, run by Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen at 14 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Any age
Conditions the study is for
COVID-19
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
14 sitesin 4 countries
Study dates
1 Apr 2022to 17 Jun 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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/
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  • 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:
  • Patients with at least one of the following acquired immune deficiencies
  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

14 sites in 4 countries.

14 sites in 4 countries

Germany11 sites

  • Charité Medizinische Klinik IV

    Berlin, 10117

  • Universitätsklinikum Brandenburg

    Brandenburg an der Havel, Brandenburg, 14770

  • Klinikum Chemnitz gGmbH

    Chemnitz, 09116

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, Hesse, 60590

  • Stauferklinikum Schwäbisch Gmünd

    Mutlangen, Baden-Wurttemberg, 73527

  • Elblandkliniken Riesa

    Riesa, Saxony, 01589

  • Klinikum Stuttgart

    Stuttgart, Baden-Wurttemberg, 70174

  • Diakonie-Klinikum Stuttgart

    Stuttgart, Baden-Wurttemberg, 70176

  • Uniklinikum Tübingen

    Tübingen, Baden-Wurttemberg, 72076

  • Institut für Klinische Transfusionsmedizin (IKT)

    Ulm, Baden-Wurttemberg, 89081

  • Uniklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

France1 site

  • CHU Besançon

    Besançon, 25000

Other trials in France

Netherlands1 site

  • Erasmus Medical Center

    Rotterdam, 3000CA

Other trials in Netherlands

United Kingdom1 site

  • NHS Blood and Transplant

    Oxford

Other trials in United Kingdom

About this study

Official 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)
Read the detailed description

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.

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
COVID-19
Being tested
Current standard of care and COVID-19 convalescent and vaccinated plasma, Current standard of care
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Current standard of care and COVID-19 convalescent and vaccinated plasmaBiological

    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 careOther

    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.

Study groups in NCT05271929
Study groupRoleWhat they receive
Current standard of careActive comparatorStandard 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.
Receives: Other: Current standard of care
Current standard of care and convalescent plasmaExperimentalCurrent standard of care and the infusion of two plasma units collected from two different COVID-19 convalescent patients.
Receives: Biological: Current standard of care and COVID-19 convalescent and vaccinated plasma

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Day 28

Secondary outcomes (14)

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

    Measured: Day 14

  2. 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

    Measured: Day 14 and Day 28

  3. All-cause mortality

    Measured: Day 28, 90, 180

  4. Proportion of patients with supplemental oxygen

    Measured: Day 14, 28

  5. Proportion of patients with non-invasive ventilation

    Measured: Day 14, 28

  6. Proportion of patients with intubation and mechanical ventilation

    Measured: Day 14, 28

  7. 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)

    Measured: Day 14, 28

  8. Duration of hospital admission censored at 28 days

    Measured: Day 28

  9. Proportion of patients with admission to ITU

    Measured: Day 14, 28

  10. Duration of ITU admission censored at 28 days

    Measured: Day 28

  11. Proportion of patients with long COVID-19 symptoms and time to recovery

    Measured: Day 28, 180

  12. 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.

    Measured: Day 28, 180

  13. Number of Serious Adverse Events

    Grade 3/4 adverse events and AE unexpected for their nature, onset, evolution, severity or frequency

    Measured: 72 hours

  14. Number of Participants with arterial and venous thromboembolic events

    Measured: Day 28, 90, 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2022
  2. Study start1 Apr 2022
  3. Primary completion18 Jan 2024
  4. Study completion17 Jun 2024

Why it stopped: Due to the significant decline in the number of newly diagnosed infections and the difficulties in opening new centers in the outgoing pandemic, recruitment declined. The Data Safety Monitoring Board recommended to stop the trial.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05271929
Sponsor's protocol ID
COVIC-19
Acronym
COVIC-19
Status last verified
Oct 2024
First submitted
3 Mar 2022
Last updated
29 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40937925

  • 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.

    PubMed 40020259

  • 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.

    PubMed 37105693

Questions about this trial

What is this clinical trial studying?

A Phase 3 study of COVID-19, run by Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen at 14 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Germany, France, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to the significant decline in the number of newly diagnosed infections and the difficulties in opening new centers in the outgoing pandemic, recruitment declined. The Data Safety Monitoring Board recommended to stop the trial.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with hospitalisation with progressive COVID-19 symptoms or death (time frame: Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05271929, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024.

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