NCT04589949

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

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
420

participants targeted

Target at P50-P75 for phase_3 covid19

Timeline
Completed

Started Oct 2020

Typical duration for phase_3 covid19

Geographic Reach
1 country

11 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 12, 2020

Completed
Same day until next milestone

Study Start

First participant enrolled

October 12, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 19, 2020

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2021

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2022

Completed
Last Updated

April 1, 2022

Status Verified

March 1, 2022

Enrollment Period

12 months

First QC Date

October 12, 2020

Last Update Submit

March 22, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • Highest disease status

    Highest disease status on the 5-point ordinal disease severity scale in the convP group will be compared with the FFP group.

    28 days following transfusion of convP or FFP

Secondary Outcomes (5)

  • Percentage of deaths

    28 days following transfusion of convP or FFP

  • Percentage of hospital admissions

    28 days following transfusion of convP or FFP

  • Percentage of ICU admissions

    28 days following transfusion of convP or FFP

  • Disease duration in days of symptoms

    28 days following transfusion of convP or FFP

  • Age and clinical frailty score

    28 days following transfusion of convP or FFP

Other Outcomes (2)

  • Highest disease status stratified by presence of neutralizing antibodies and by symptom duration at baseline

    28 days following transfusion of convP or FFP

  • Change in proportion of detectable SARS-Cov-2 RT-PCR results

    Day 3, 7, 14 and 28 following transfusion of convP or FFP

Study Arms (2)

ConvP

EXPERIMENTAL

300 mL convalescent plasma with a minimum of neutralizing antibodies

Biological: ConvP

FFP

ACTIVE COMPARATOR

300 mL Fresh Frozen plasma

Biological: FFP

Interventions

ConvPBIOLOGICAL

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

Also known as: convalescent plasma
ConvP
FFPBIOLOGICAL

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

Also known as: Fresh Frozen Plasma
FFP

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • years or older OR 50-69 years and 1 or more of the risk factors described in the protocol

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Erasmus Medical Center

Rotterdam, South Holland, 3000 CA, Netherlands

Location

Meander Medisch Centrum

Amersfoort, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, Netherlands

Location

University Medical Center Groningen (UMCG)

Groningen, Netherlands

Location

Spaarne Gasthuis

Haarlem, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Bernhoven Hospital

Uden, Netherlands

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Bart Rijnders, MD, PhD

    Erasmus Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

October 12, 2020

First Posted

October 19, 2020

Study Start

October 12, 2020

Primary Completion

October 1, 2021

Study Completion

March 1, 2022

Last Updated

April 1, 2022

Record last verified: 2022-03

Locations