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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Covid19

Intervention / Treatment
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* Biological: ConvP
* Biological: FFP


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ConvP<br>300 mL convalescent plasma with a minimum of neutralizing antibodies | Biological: ConvP<br>* 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<br>* Other names: convalescent plasma;|
| Active Comparator: FFP<br>300 mL Fresh Frozen plasma | Biological: FFP<br>* Infusion of thawed non-convalescent plasma Plasma will be administered according to the Erasmus Medical Center quality protocol regarding the use of blood products<br>* Other names: Fresh Frozen Plasma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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