Hyperimmune Plasma in Patients With COVID-19 Severe Infection

COVID-19 Clinical Trial

— COV2-CP  

Official title:

Efficacy and Safety of Hyperimmune Plasma Treatment in Patients With COVID-19 Severe Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04385043
• Other study ID #: Covid-19 convalescent plasma
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 1, 2020
• Est. completion date: May 15, 2021

Study information

• Verified date: May 2020
• Source: University of Catanzaro
• Contact: Gabriella Talarico, MD
• Phone: 0961883111
• Email: trasfusionale[@]aocz.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: May 15, 2021
• Est. primary completion date: October 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• Infection

Intervention

Other:
• plasma hyperimmune
patients will receive this as add on therapy

Drug:
• standard therapy
patients will receive only standard therapy for Covid-19 infection

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Policlinico Mater Domini	Catanzaro
Italy	Azienda Ospedaliera Pugliese Ciaccio Catanzaro	Catanzaro
Italy	Azienda Ospedaliera Annunziata	Cosenza
Italy	Azienda Sanitaria Provinciale	Crotone
Italy	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Calabria
Italy	Azienda Sanitaria Provinciale	Vibo Valentia

Sponsors (5)

Lead Sponsor	Collaborator
University of Catanzaro	Annunziata Hospital, Cosenza, Italy, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Azienda Ospedaliera Policlinico "Mater Domini", Azienda Sanitaria Provinciale Di Catanzaro

Country where clinical trial is conducted

Italy, 

References & Publications (7)

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. Fe — View Citation

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. — View Citation

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. — View Citation

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 Mar 4. — View Citation

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..

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 — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	decrease in mortality	Statistically significant reduction (P <0.05) of mortality in the group of patients treated with hyperimmune plasma vs patients treated with standard therapy.	30 days
Secondary	lymphocytes	Statistically significant increase (P <0.05) of lymphocyte levels after 7 and 14 days after the start of treatment with hyperimmune plasma (treated group), compared to the control group.	7 and 14 days
Secondary	PCR levels vs control	Statistically significant reduction (P <0.05) of plasma levels of reactive protein C (expressed as mg/L), 7 and 14 days after the start of treatment with hyperimmune plasma vs standard therapy (group control)	7 and 14 days
Secondary	PCR levels vs before treatment	Statistically significant reduction (P <0.05) of plasma levels of reactive protein C (expressed as mg/L), 7 and 14 days after the start of treatment with hyperimmune plasma vs the same patients before the beginning of the treatment	7 and 14 days
Secondary	AB levels and clinical improvement	Significant Correlation (P<0.05) between hyperimmune plasma antibody levels and clinical improvement time (expressed in days)	30 days
Secondary	Inflammatory cytokines vs controls	Statistically significant reduction (P <0.05) of plasma levels of IL-6 (expressed as pg/mL) and TNF-alpha (expressed as pg/mL), 7 and 14 days after the start of treatment with hyperimmune plasma vs standard therapy (group control)	7 and 14 days
Secondary	Inflammatory cytokines vs before treatment	Statistically significant reduction (P <0.05) of plasma levels of IL-6 (expressed as pg/mL) and TNF-alpha (expressed as pg/mL), 7 and 14 days after the start of treatment with hyperimmune plasma vs the same patients before the beginning of the treatment	7 and 14 days

External Links

•   reference 6
•   reference 9