Clinical trial NCT04589949: Early Convalescent Plasma Therapy for High-risk Patients With COVID-19 in Primary Care (the CoV-Early Study)
Official title: Early Convalescent Plasma Therapy for High-risk Patients With COVID-19 in Primary Care (the CoV-Early Study)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Covid19
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Prothya Biosolutions
name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Leiden University Medical Center
First posted: 2020-10-19
Enrollment: 420
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Highest disease status
timeFrame: 28 days following transfusion of convP or FFP
Secondary outcomes:
measure: Percentage of deaths
timeFrame: 28 days following transfusion of convP or FFP
measure: Percentage of hospital admissions
timeFrame: 28 days following transfusion of convP or FFP
measure: Percentage of ICU admissions
timeFrame: 28 days following transfusion of convP or FFP
measure: Disease duration in days of symptoms
timeFrame: 28 days following transfusion of convP or FFP
measure: Age and clinical frailty score
timeFrame: 28 days following transfusion of convP or FFP
Other outcomes:
measure: Highest disease status stratified by presence of neutralizing antibodies and by symptom duration at baseline
timeFrame: 28 days following transfusion of convP or FFP
measure: Change in proportion of detectable SARS-Cov-2 RT-PCR results
timeFrame: Day 3, 7, 14 and 28 following transfusion of convP or FFP
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Uden
country: Netherlands
facility: Bernhoven Hospital
Study officials:
affiliation: Erasmus Medical Center
name: Bart Rijnders, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.