Hyperimmune Plasma in Patients With COVID-19 Severe Infection

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Other: plasma hyperimmune
* Drug: standard therapy


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: plasma-hyperimmune<br>enrolled patients (n=200) with severe Covid-19 infection will receive a treatment with plasma hyperimmune add on to the standard therapy | Other: plasma hyperimmune<br>* patients will receive this as add on therapy<br>Drug: standard therapy<br>* patients will receive only standard therapy for Covid-19 infection<br>|
| Active Comparator: standard therapy<br>enrolled patients (n=200) with severe Covid-19 infection will receive a treatment with the standard therapy | Drug: standard therapy<br>* patients will receive only standard therapy for Covid-19 infection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| AB levels and clinical improvement | Significant Correlation (P<0.05) between hyperimmune plasma antibody levels and clinical improvement time (expressed in days) | 30 days | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe Covid-19, severe coronavirus-2, plasma hyperimmune, convalescent plasma