Hyperimmune Plasma in Patients With COVID-19 Severe Infection

NCT ID: NCT04385043

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2021-05-15

Brief Summary

Passive immunotherapy through plasma infusion of convalescent subjects - convalescent plasma - or "hyperimmune" plasma was one of the most widespread and effective anti-infective treatments in the pre-antibiotic era and one of the founding pillars of immunology, and has also been used during the SARS (2002-2003) and Ebola (2014-2016) viral epidemy for which there were no alternative immunoprophylactic or therapeutic interventions.

To date, there are not proven etiological therapies for SARS-CoV-2 infection, the agent responsible for the disease called Covid-19. Among those subjected to clinical studies during the current epidemic in China, hyperimmune plasma appears to be one of the most rational and promising.

The objective of this study will be to evaluate the efficacy and safety of the hyperimmune plasma administered add-on to the anti-Covid-19 treatment (standard therapy) according to clinical practice in patients with severe Covid-19 infection, compared to patients with severe Covid-19 infection treated only with standard therapy.

Detailed Description

Passive immunotherapy through plasma infusion of convalescent subjects - convalescent plasma - or "hyperimmune" plasma was one of the most widespread and effective anti-infective treatments in the pre-antibiotic era and one of the founding pillars of immunology. Immunoprophylaxis represents an irreplaceable protection for post-exposure prevention of several viral infections such as measles, hepatitis B and rabies. Recently, the use of convalescent plasma for therapeutic purposes has been re-evaluated during the SARS (2002-2003) and Ebola (2014-2016) epidemic caused by serious viral infections for which there were no immunoprophylactic or therapeutic interventions. alternative. The results of these experimental interventions, despite the limited number and the often anecdotal character, have shown promise even if not conclusive. In the case of SARS, the first human respiratory disease caused by a Coronavirus, treatment with convalescent plasma was associated with a 23% reduction in mortality and with the best results if administered at an early stage of the disease. In addition, all the evidence available in the literature has confirmed the safety of convalescent plasma treatments, in line with what has already been observed in the transfusion practice with Fresh Frozen Plasma.

As is known, there are currently no proven etiological therapies to combat SARS-CoV-2 infection, the agent responsible for the disease called Covid-19. Among those subjected to clinical studies during the current epidemic in China, hyperimmune plasma appears to be one of the most rational and promising.

Waiting for the numerous clinical trials underway especially in Asia and accessible on the website http://apps.who.int/trialsearch/default.aspx to define if and to what extent this therapeutic contribution improves the prognosis of patients suffering from serious forms of infections from SARS-Co-2, the clinical guidelines of the People's Republic of China, already provide for the use of hyperimmune plasma with the indication "in rapidly progressive disease, severe and very severe form" and by the FDA .

As regards the technical protocols for the preparation of hyperimmune plasma for clinical use in the literature, precise references are available in particular for the preparation, qualification, viral inactivation and dosage of hyperimmune plasma for the treatment of viral epidemic infections such as MERS and Ebola and which can also be validated and used for the preparation of plasma from convalescent patients for Covid-19.

From the above, the objective of this study will be to evaluate the efficacy and safety of the hyperimmune plasma administered add-on to the anti-Covid-19 treatment (standard therapy) according to clinical practice in patients with severe Covid-19 infection, compared to patients with severe Covid-19 infection treated only with standard therapy.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

plasma-hyperimmune

enrolled patients (n=200) with severe Covid-19 infection will receive a treatment with plasma hyperimmune add on to the standard therapy

Group Type: EXPERIMENTAL

plasma hyperimmune

Intervention Type: OTHER

patients will receive this as add on therapy

standard therapy

Intervention Type: DRUG

patients will receive only standard therapy for Covid-19 infection

standard therapy

enrolled patients (n=200) with severe Covid-19 infection will receive a treatment with the standard therapy

Group Type: ACTIVE_COMPARATOR

standard therapy

Intervention Type: DRUG

patients will receive only standard therapy for Covid-19 infection

Interventions

plasma hyperimmune

patients will receive this as add on therapy

Intervention Type: OTHER

standard therapy

patients will receive only standard therapy for Covid-19 infection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Inclusion Criteria:

• inclusion criteria for donors: null-gravid, with a negative history of transfusion of blood components; possibility to sign the informed consent
• inclusion criteria for Covid-19 infected patients: serious Covid-19 infection, possibility to sign the informed consent (also through the legal tutor)

Exclusion Criteria:

• exclusion criteria for donors: presence of pregnancy, recent history of transfusion of blood components, < 18 years.
• exclusion criteria for Covid-19 infected patients: non serious Covid-19 infection, impossibility to sign the informed consent (also through the legal tutor)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliera Universitaria Mater Domini, Catanzaro

OTHER

Sponsor Role: collaborator

Azienda Sanitaria Provinciale Di Catanzaro

OTHER

Sponsor Role: collaborator

Annunziata Hospital, Cosenza, Italy

OTHER

Sponsor Role: collaborator

Azienda Ospedaliera Bianchi-Melacrino-Morelli

OTHER

Sponsor Role: collaborator

University of Catanzaro

OTHER

Sponsor Role: lead

Responsible Party

Luca Gallelli

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Azienda Ospedaliera Policlinico Mater Domini

Catanzaro, , Italy

Site Status: RECRUITING

Azienda Ospedaliera Pugliese Ciaccio Catanzaro

Catanzaro, , Italy

Site Status: RECRUITING

Azienda Ospedaliera Annunziata

Cosenza, , Italy

Site Status: RECRUITING

Azienda Sanitaria Provinciale

Crotone, , Italy

Site Status: RECRUITING

Azienda Ospedaliera Bianchi Melacrino Morelli

Reggio Calabria, , Italy

Site Status: RECRUITING

Azienda Sanitaria Provinciale

Vibo Valentia, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Gabriella Talarico, MD

Role: CONTACT

trasfusionale@aocz.it

0961883111

Facility Contacts

Federico Longhini, MD

Role: primary

longhini@unicz.it

0961712111

Andrea Dominijanni, MD

Role: primary

trasfusionale@aocz.it

0961883111

Francesco Zinno, MD

Role: primary

f.zinno@aocs.it

0984 6811

Patrizia Leonardo, MD

Role: primary

centro.trasfusionale@asp.crotone.it

0962924471

Alfonso Trimarchi, MD

Role: primary

atrimarchi@aorc.it

0965 730011

Paola Grandini, MD

Role: primary

trasfusionale@aspvv.it

0963-962111

References

Marano G, Vaglio S, Pupella S, Facco G, Catalano L, Liumbruno GM, Grazzini G. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 2016 Mar;14(2):152-7. doi: 10.2450/2015.0131-15. Epub 2015 Nov 6.

Reference Type: BACKGROUND

PMID: 26674811 (View on PubMed)

Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. doi: 10.1016/S1473-3099(20)30141-9. Epub 2020 Feb 27. No abstract available.

Reference Type: BACKGROUND

PMID: 32113510 (View on PubMed)

Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545-1548. doi: 10.1172/JCI138003. No abstract available.

Reference Type: BACKGROUND

PMID: 32167489 (View on PubMed)

Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.

Reference Type: RESULT

PMID: 25030060 (View on PubMed)

Linee Guida Cinesi sulla Gestione di COVID-19 Versione 7° Pubblicate in data 3/3/2020 dalla Commissione della Salute Nazionale della R.P.C..

Reference Type: RESULT

Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.

Reference Type: RESULT

PMID: 26618098 (View on PubMed)

Dean CL, Hooper JW, Dye JM, Zak SE, Koepsell SA, Corash L, Benjamin RJ, Kwilas S, Bonds S, Winkler AM, Kraft CS. Characterization of Ebola convalescent plasma donor immune response and psoralen treated plasma in the United States. Transfusion. 2020 May;60(5):1024-1031. doi: 10.1111/trf.15739. Epub 2020 Mar 4.

Reference Type: RESULT

PMID: 32129478 (View on PubMed)

Other Identifiers

Covid-19 convalescent plasma

Identifier Type: -

Identifier Source: org_study_id