Early Convalescent Plasma Therapy for High-risk Patients With COVID-19 in Primary Care (the CoV-Early Study)

NCT ID: NCT04589949

Last Updated: 2022-04-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 420 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-12
• Study Completion Date: 2022-03-01

Brief Summary

An effective, widely available, and safe treatment that can decrease the duration, severity and fatality of COVID-19 is urgently needed. Also, in the most affected regions the pressure on health care systems including ventilator support capacity can be a limiting factor for survival. Initial studies including from our group indicate that administering convalescent plasma containing high titers of neutralizing antibodies to COVID-19 patients who are already relatively late during the disease course after hospital admission is not effective, which can be explained by high titers of autologous antibodies present in patients. Thus, the antiviral capacity of convalescent plasma is hypothesized to be best positioned early in the disease course and in patients at increased risk for a severe disease course. If effective, any treatment that decreases the need for hospital admission is very valuable but so far, no COVID-19 treatment has been shown to prevent clinical deterioration when given before patients are admitted to the hospital.

Primary objective:

To evaluate the efficacy, feasibility and safety following the administration of convalescent plasma (ConvP) as a therapy for outpatients diagnosed with COVID-19 at increased risk for an unfavourable clinical outcome and within 7 days after symptom onset.

Study design:

This trial is a nationwide multicenter, double blind, randomized controlled trial in the Netherlands. Patients will be randomized between the transfusion of 300mL of convP versus regular fresh frozen plasma (FFP).

Patient population:

Patients with polymerase chain reaction (PCR) confirmed COVID disease with less than 8 days of symptoms, age 70 or older or 50-69 years with at least 1 additional risk factor for severe COVID-19 are eligible.

Intervention:

300mL of convP with a minimum level of neutralizing antibodies.

A total of 690 patients will be included. Expected duration of accrual: 18-24 months Duration of follow up :Day 28 for the primary endpoint

Detailed Description

Secondary (exploratory) objectives

• To evaluate the impact of 300mL convP on mortality
• To evaluate the impact of 300mL convP on hospital admission
• To evaluate the impact of 300mL convP on admission to ICU
• To evaluate the impact of 300mL convP on duration of symptoms
• To evaluate the impact of 300mL convP in relation to the age and clinical frailty of the patient

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ConvP

300 mL convalescent plasma with a minimum of neutralizing antibodies

Group Type: EXPERIMENTAL

ConvP

Intervention Type: BIOLOGICAL

Infusion of plasma retrieved from donors with a history of PCR proven symptomatic COVID.

Plasma will be administered according to the Erasmus MC KIS protocol regarding the use of blood products

FFP

300 mL Fresh Frozen plasma

Group Type: ACTIVE_COMPARATOR

FFP

Intervention Type: BIOLOGICAL

Infusion of thawed non-convalescent plasma Plasma will be administered according to the Erasmus Medical Center quality protocol regarding the use of blood products

Interventions

ConvP

Infusion of plasma retrieved from donors with a history of PCR proven symptomatic COVID.

Plasma will be administered according to the Erasmus MC KIS protocol regarding the use of blood products

Intervention Type: BIOLOGICAL

FFP

Infusion of thawed non-convalescent plasma Plasma will be administered according to the Erasmus Medical Center quality protocol regarding the use of blood products

Intervention Type: BIOLOGICAL

Other Intervention Names

convalescent plasma; Fresh Frozen Plasma

Eligibility Criteria

Inclusion Criteria

• RT-PCR-confirmed COVID-19.
• Symptomatic (e.g but not limited to fatigue, fever, cough, dyspnoea, loss of taste or smell, diarrhea, falls or confusion)
• 70 years or older OR 50-69 years and 1 or more of the risk factors described in the protocol

Exclusion Criteria

• Life expectancy <28 days in the opinion of the treating physician
• Patient or legal representative is unable to provide written informed consent
• Symptomatic for 8 days or more
• Being admitted to the hospital at the informed consent procedure
• Known previous history of transfusion-related acute lung injury
• Known Immunoglobulin A (IgA) deficiency

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prothya Biosolutions

INDUSTRY

Sponsor Role: collaborator

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Bart Rijnders

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bart Rijnders, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Rijnstate Ziekenhuis

Arnhem, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

Groene Hart Ziekenhuis

Gouda, , Netherlands

University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Spaarne Gasthuis

Haarlem, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Sint Antonius Ziekenhuis

Nieuwegein, , Netherlands

Bernhoven Hospital

Uden, , Netherlands

Countries

Netherlands

References

Millat-Martinez P, Gharbharan A, Alemany A, Rokx C, Geurtsvankessel C, Papageorgiou G, van Geloven N, Jordans C, Groeneveld G, Swaneveld F, van der Schoot E, Corbacho-Monne M, Ouchi D, Piccolo Ferreira F, Malchair P, Videla S, Garcia Garcia V, Ruiz-Comellas A, Ramirez-Morros A, Rodriguez Codina J, Amado Simon R, Grifols JR, Blanco J, Blanco I, Ara J, Bassat Q, Clotet B, Baro B, Troxel A, Zwaginga JJ, Mitja O, Rijnders BJA; CoV-Early study group; COnV-ert study group. Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients. Nat Commun. 2022 May 11;13(1):2583. doi: 10.1038/s41467-022-29911-3.

Reference Type: DERIVED

PMID: 35546145 (View on PubMed)

Other Identifiers

NL74972.078.20

Identifier Type: -

Identifier Source: org_study_id