Convalescent Plasma for Treatment of COVID-19

NCT04649879 | Completed Phase 2 DMC

• 1 other identifier: CP3
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 3

Brief Summary

Convalescent plasma has been shown to be safe and effective for treatment of several diseases. Preliminary data indicate that it is safe for treatment of COVID-19. We found that viremia upon admission identifies patients at 7 fold increased risk of admission to intensive care and 8 fold increased risk of death. CP treatment appeared to result in rapid viral clearance in a small case series. CP appeared to be well tolerated in a phase I study in which patients only received one dose of CP and a phase II study in which CP was given until viremia disappeared (unpublished data). Randomised controlled studies assessing the efficacy of CP are lacking and thus the efficacy of CP is unknown. Preliminary data indicate that treatment should be given early, prior to development of severe illness. Detection of viremia upon admission identifies a group at high risk of severe disease and death that has the most to benefit from CP. Phase II study data indicates that treatment should be given until SARS-CoV-2 is no longer detected in serum and the donor antibody neutralization titres should be ≥1/640. A randomised controlled trial in which viremic patients are treated with CP with the equivalent of an antibody titre ≥1/640 is thus required to determine if CP can be an effective COVID-19 treatment.

Conditions

Covid19

Keywords

COVID-19 convalescent plasma treatment; SARS-CoV-2 infection; Viremia

Outcome Measures

Primary Outcomes (1)

• COVID-19 related mortality within 28 days

  Death of a study participant within 28 days.

  Measured 28 days after inclusion into the study.

Secondary Outcomes (5)

• COVID-19 related mortality within 60 days

  Measured 60 days after inclusion into the study.

• Requirement of invasive ventilation or Pao2/FiO2 ≤ 70 for ≥ 12 hours in the case of patients not eligible for intensive care

  Until discharged from the hospital, up to 2 months

• Adverse events

  The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.

• Dose of plasma needed to clear viremia

  28 days

• Time to clearance of viremia

  Until discharged from the hospital, up to 2 months

Study Arms (2)

Convalescent plasma treatment

EXPERIMENTAL

* Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions. * If steroid therapy has not already been initiated, betamethasone 3 mg daily will be given concomitantly with steroid therapy or longer if clinically indicated but for a maximum of 10 days.

Biological: SARS-CoV-2 convalescent plasma

Control

ACTIVE COMPARATOR

Standard of care for COVID-19 patients.

Other: Standard of care

Interventions

SARS-CoV-2 convalescent plasma BIOLOGICAL

Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions. CP will be given as a slow infusion over 2 hours. CP neutralization titre of ≥ 1/640 or an ELISA reactivity against the Spike protein of SARS-CoV-2 by the Euroimmun commercial assay \>9 is desired. New antibody tests are under development and can be used instead if equivalence to neutralization or Euroimmun ELISA is demonstrated.

Convalescent plasma treatment

Standard of care OTHER

Standard of care as determined by hospital practices for COVID-19 patients.

Control

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18
• Admitted to a study hospital
• Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples and blood
• Written informed consent after meeting with a study physician and ability and willingness to complete follow up

You may not qualify if:

• No matching plasma donor (Exact matching in the ABO system is required)
• Unavailability of plasma
• Estimated glomerular filtration rate \<30 (kidney failure stage III or more)
• Pregnancy (urinary-hcg)
• Breast feeding
• Inability to give informed consent

Sponsors & Collaborators

• Joakim Dillner: lead
• Karolinska Institutet: collaborator
• Danderyd Hospital: collaborator
• Falu Hospital: collaborator

Study Sites (3)

Department of Infectious Disease, Falu Hospital

Falun, Dalarn, 79182, Sweden

Location

Department of Geriatrics, Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Danderyd Hospital

Stockholm, 18257, Sweden

Location

Related Publications (1)

• Dillner J, Ursing J. Convalescent plasma for treatment of COVID-19: study protocol for an open randomised controlled trial in Sweden. BMJ Open. 2021 Dec 8;11(12):e048337. doi: 10.1136/bmjopen-2020-048337.

  PMID: 34880010 DERIVED

MeSH Terms

Conditions

COVID-19; Viremia

Interventions

COVID-19 Serotherapy; Standard of Care

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; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Infectious Disease Epidemiology; Director of R&D

Model Details: Patients will be randomised 2:1 to treatment with convalescent plasma and standard of care only. Randomisation is by random permutated blocks using Redcap or equivalent.

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 2, 2020
• Study Start: December 3, 2020
• Primary Completion: January 26, 2022
• Study Completion: January 26, 2022
• Last Updated: February 9, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

SE (3)