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

Covid19 Clinical Trial

— CoV-Early  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04589949
• Other study ID #: NL74972.078.20
• Status: Terminated
• Phase: Phase 3
• Start date: October 12, 2020
• Est. completion date: March 1, 2022

Study information

• Verified date: March 2022
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 420
• Est. completion date: March 1, 2022
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• 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
• 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

Locations

Country	Name	City	State
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	Erasmus Medical Center	Rotterdam	Zuid-Holland
Netherlands	Bernhoven Hospital	Uden

Sponsors (4)

Lead Sponsor	Collaborator
Erasmus Medical Center	Leiden University Medical Center, Prothya Biosolutions, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Highest disease status stratified by presence of neutralizing antibodies and by symptom duration at baseline	Analysis of primary endpoint following transfusion of convP versus FFP stratified by the presence of neutralizing antibodies at baseline and by symptom duration at baseline.	28 days following transfusion of convP or FFP
Other	Change in proportion of detectable SARS-Cov-2 RT-PCR results	Change in proportion of detectable SARS-CoV-2 RT-PCR results at day 3, 7, 14 and 28 following transfusion according to the presence of neutralizing antibodies at baseline	Day 3, 7, 14 and 28 following transfusion of convP or FFP
Primary	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	Percentage of deaths	Percentage of deaths in the convP group compared to the FFP group	28 days following transfusion of convP or FFP
Secondary	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
Secondary	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
Secondary	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
Secondary	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