Convalescent Plasma in the Treatment of Covid-19

NCT ID: NCT04730401

Last Updated: 2022-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 390 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-27
• Study Completion Date: 2023-01-30

Brief Summary

This study investigates the possible adverse effects and effectiveness of convalescent plasma for patients infected with SARS-CoV-2. Following provision of informed consent, patients will be randomized into three groups: High-titre convalescent plasma, low-titre convalescent plasma or placebo. Primary outcomes of the study will cover safety and either intubation or initiation of systemic corticosteroids. Safety information collected will include serious adverse events judged to be related to administration of convalescent plasma. Microbiological and other laboratory parameters will be followed up.

Detailed Description

SARS-CoV-2 pandemic presents a serious global public health threat urgently requiring both prophylactic and therapeutic interventions. The entry of SARS-CoV-2 into human cells involves a binding between its spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) receptor on human cells. Convalescent sera of Covid-19 patients have been shown to contain SARS-CoV-2-neutralizing antibodies. Accordingly, recovered patients are presumed to be immune to re-infection. Use of convalescent plasma as treatment warrants research, which is supported by the European Commission. Convalescent plasma (CP) therapy is a classical adaptive immunotherapy. It has been applied to prevention and treatment of various infectious diseases: evidence of success has been accumulated e.g. on treatment of SARS, MERS, and 2009 H1N1, for which satisfactory efficacy and safety have been shown.

The investigators will select as donors for CP therapy patients recovered from Covid-19 with a high neutralizing antibody titre who meet normal blood donor eligibility criteria. The donors will be recruited among participants of ongoing Covid-19 immunity studies (Clin-Covid, Commun-Covid) and/or from Finnish Red Cross Blood Service (FRCBS) blood donors.

CP will be prepared from the blood of eligible donors at the FRCBS according to previous protocols and the European guidelines for fresh frozen plasma. After the screening test results required for product release (HCV, HBV, HIV, ABO, Syphilis) are available, the units will be released. All donors will be screened for type-I-Interferon antibodies and women will be screened for HLA-antibodies. The units will be labelled with convalescence plasma labels including ICCBBA/ISBT compliant product codes. The plasma units will be frozen to -25°C within 6 hours from collection. Prior to freezing 3 ml of CP will be separated and divided in 3 aliquots to be stored, for possible later analysis.

Patients admitted to ward at HUH will be randomized 1:1:1 into three groups which will be given 1) high-titre convalescent plasma (HCP), 2) low-titre convalescent plasma (LCP) or 3) placebo. The plasma preparations and placebo will be given as one 200 mL infusion. ABORh blood group will be determined from patients prior to transfusion according to normal transfusion protocols of the hospital. The study will be double-blinded with saline as placebo given to groups three. The primary outcomes of the study will cover safety and intubation/initiation of systemic corticosteroids. AEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo. Thromboembolic and cardiovascular events will be recorded as AEs or SAEs up to 7 days after administration of CP / placebo. SAEs will be reviewed, recorded and reported up to 7 days after administration of CP / placebo. In case of respiratory failures classified as SAEs, the reporting period is only up to 12 hours after administration of CP / placebo.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

High-titre CP

200mL high-titre CP on admittance

Group Type: EXPERIMENTAL

Convalescent plasma from COVID-19 donors

Intervention Type: BIOLOGICAL

Convalescent plasma from COVID-19 donors

low-titre CP

200ml low-titre CP on admittance

Group Type: ACTIVE_COMPARATOR

Convalescent plasma from COVID-19 donors

Intervention Type: BIOLOGICAL

Convalescent plasma from COVID-19 donors

Placebo

200mL saline as placebo on admittance

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

200mL saline

Interventions

Convalescent plasma from COVID-19 donors

Convalescent plasma from COVID-19 donors

Intervention Type: BIOLOGICAL

Placebo

200mL saline

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Acute Covid-19 disease at the time of recruitment laboratory-confirmed by upper respiratory tract PCR
• Patient recently (0-4 days earlier) admitted to hospital due to Covid-19 infection
• Symptom onset 10 days before recruitment (if symptom onset unknown the duration is calculated from positive PCR-test)
• the day should be recorded from the duration of the Covid-19 symptoms/positive test result
• The dose of LMWH thromboprofylaxis should be recorded
• Written informed consent.

Exclusion Criteria

• Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of IMP; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded ( inhaled or topical steroids allowed)
• Regular (daily), systemic administration of corticosteroids at the time on inclusion (inhaled or topical corticosteroids are allowed)
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• Pregnancy or lactation.
• Alcohol or drug abuse.
• Suspected non-compliance.
• Presence of VTE, including pulmonary embolism or other manifestations of thrombosis
• Use of any investigational drug (other than hydroxychloroquine) or vaccine within 30 days prior to first dose of study vaccine or planned use during study period.
• Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction as judged by investigator.
• Known immunoglobulin A (IgA) deficiency
• Existing treatment limitations: do-not-resuscitate (DNR) order or withholding treatment in ICU
• Any other criteria which, as judged by investigator, might compromise a patient's well-being or ability to participate in the study or its outcome.
• Active malignant disease
• CP not available for patients blood type
• Patient cannot assign written consent
• No personnel available for CP of placebo transfusion

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Finnish Red Cross Blood Service

OTHER

Sponsor Role: collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anu Kantele

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anu Kantele, MD,Prof

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Central Hospital

Locations

Helsinki University Central Hospital

Helsinki, Uusimaa, Finland

Countries

Finland

Other Identifiers

Plasma_Covid-19

Identifier Type: -

Identifier Source: org_study_id