Convalescent Plasma Therapy - Zurich Protocol

NCT ID: NCT04869072

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-29
• Study Completion Date: 2021-03-30

Brief Summary

This is an open-label, single-center, phase I study to assess the safety and efficacy of convalescent plasma therapy (CPT) obtained from donors who were tested positive for SARS-CoV-2 and fully recovered from the infection and administered to patients who are infected with the new coronavirus and present dyspnea or a poor prognosis

Detailed Description

The outbreak of a new highly contagious and life-threatening infective disease was first reported in China in December 2019. Regardless of the undertaken containing measures, its spreading could not be effectively stopped and currently we are confronting the pandemic diffusion of a newly identified Coronavirus (SARS-CoV-2) (1). This causes a systemic disease, known as (Coronavirus Disease-19) COVID-19, characterised by a broad spectrum of clinical manifestations, including ineffective hyper-inflammation and severe pneumonia, with provisional epidemiologic data indicating a mortality rate of 0.1-15% (2). Do to the lack of vaccination, specific anti-virus sera or monoclonal antibodies, the therapeutic efforts to limit COVID-19 mostly rely on the empirical use of anti-viral drugs. Therefore, being the option of an active immunisation not available and because of the controversial efficacy of the available anti-viral therapies (3), we suggest the option of a passive immunisation for those patients who are infected with the new coronavirus and present dyspnea or a poor prognosis. The use of convalescent plasma, i.e. plasma obtained from donors who were tested positive for SARS-CoV-2 and fully recovered from the infection, could provide a rapid protection, limiting the observed evolution of COVID-19 towards life-threating manifestations (7-9).

When carried on according to standardised measures, the transfusion of plasma is highly safe (10-11) and we assume that products containing anti- SARS-CoV- 2 antibodies will provide the recipients a passive immunity through different mechanisms, including viral neutralisation, antibody-dependent cellular cytotoxicity and/or phagocytosis.

Conditions

COVID-19

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Convalescent plasma

Convalescent plasma will be delivered as FFP. Three units of 200ml CP/FFP harvested from one donor will be transfused to one recipient, i.e. there will be a match between donor and recipient and each recipient will receive CP/FFP only from one donor.

CP/FFP will be administered intravenously at the infusion rate of 100ml/hour, starting from day 0, with a new transfusion every 24 hours, for a total of 3 transfusions (see scheme).

Intervention Type: DRUG

Other Intervention Names

Fresh Frozen Plasma (FFP)

Eligibility Criteria

Inclusion Criteria

A) Proven Sars-CoV-2 by PCR and hospitalization for COVID-19 in combination with either (1) or (2):

1. Age ≥50

AND (at least one):

• Pre-existing cardiovascular disease
• Diabetic disease
• Immunodeficiency/immunosuppression
• Neoplastic disease
• COPD or chronic liver disease or chronic renal failure

2. Age ≥18

AND (at least one):

• SpO2 ≤ 94% on room air or requiring supplemental oxygen at screening
• Typical changes on chest x-ray and/or lung-CT scan
• Immunosuppression or neoplastic disease

B) Informed Consent as documented by signature (Appendix Informed Consent Form) of the patient or, in case of inability, of the next relative/care-taking person. In the latter case, an independent doctor will also be involved and her/his signature will be required in order to enrol the patient.

Exclusion Criteria

1. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product (FFP)

2. Known IgA deficiency

3. Cytokine Release Syndrome grade ≥3 (see score)*

4. ARDS

5. Patients already hospitalized in intensive care unit and/or already receiving mechanical ventilation

6. Known or suspected non-compliance, drug or alcohol abuse

7. Previous enrolment into the current study

8. Enrolment of the investigator, his/her family members, employees and other dependent persons

9. Women who are pregnant or breast feeding

10. Intention to become pregnant during the course of the study

11. Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Please note that female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Markus Manz, Professor

Role: STUDY_CHAIR

University of Zurich

Locations

University Hospital Zurich

Zurich, , Switzerland

Countries

Switzerland

References

Marconato M, Abela IA, Hauser A, Schwarzmuller M, Katzensteiner R, Braun DL, Epp S, Audige A, Weber J, Rusert P, Schindler E, Pasin C, West E, Boni J, Kufner V, Huber M, Zaheri M, Schmutz S, Frey BM, Kouyos RD, Gunthard HF, Manz MG, Trkola A. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response. J Clin Invest. 2022 Jun 15;132(12):e158190. doi: 10.1172/JCI158190.

Reference Type: DERIVED

PMID: 35482408 (View on PubMed)

Other Identifiers

2020-00787

Identifier Type: -

Identifier Source: org_study_id