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

Phase 3

Terminated

• Conditions: Covid19
• Interventions: Biological: FFP; Biological: ConvP

• Registration Number: NCT04589949
• Lead Sponsor: Erasmus Medical Center

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

Study Timeline

• Study Start: 2020-10-12
• Study First Submitted: 2020-10-12
• Study First Submitted QC: 2020-10-15
• Study First Posted: 2020-10-19
• Primary Completion: 2021-10-01
• Status Verified: 2022-03
• Study Completion: 2022-03-01
• Last Update Submitted: 2022-03-22
• Last Update Posted: 2022-04-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 420

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FFP	FFP	300 mL Fresh Frozen plasma
ConvP	ConvP	300 mL convalescent plasma with a minimum of neutralizing antibodies

Primary Outcome Measures

Name	Time	Method
Highest disease status	28 days following transfusion of convP or FFP	Highest disease status on the 5-point ordinal disease severity scale in the convP group will be compared with the FFP group.

Secondary Outcome Measures

Name	Time	Method
Disease duration in days of symptoms	28 days following transfusion of convP or FFP	Disease duration in days of symptoms in the convP group compared to the FFP group
Percentage of deaths	28 days following transfusion of convP or FFP	Percentage of deaths in the convP group compared to the FFP group
Percentage of hospital admissions	28 days following transfusion of convP or FFP	Percentage of hospital admissions in the convP group compared to the FFP group
Percentage of ICU admissions	28 days following transfusion of convP or FFP	Percentage of ICU admissions in the convP group compared to the FFP group
Age and clinical frailty score	28 days following transfusion of convP or FFP	Age and clinical frailty score stratified analysis of percentage of primary endpoint following transfusion of convP versus FFP.

Trial Locations

Locations (11)

Rijnstate Ziekenhuis; 🇳🇱 Arnhem, Netherlands

Amphia Ziekenhuis; 🇳🇱 Breda, 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

Erasmus Medical Center; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands

Meander Medisch Centrum; 🇳🇱 Amersfoort, Netherlands

Groene Hart Ziekenhuis; 🇳🇱 Gouda, Netherlands