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Hyperimmune Plasma in Patients With COVID-19 Severe Infection (COV2-CP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04385043
Recruitment Status : Recruiting
First Posted : May 12, 2020
Last Update Posted : May 12, 2020
Sponsor:
Collaborators:
Azienda Ospedaliera Policlinico "Mater Domini"
Azienda Sanitaria Provinciale Di Catanzaro
Annunziata Hospital, Cosenza, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli
Information provided by (Responsible Party):
Luca Gallelli, University of Catanzaro

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.


Condition or disease Intervention/treatment Phase
COVID-19 Other: plasma hyperimmune Drug: standard therapy Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Hyperimmune Plasma Treatment in Patients With COVID-19 Severe Infection
Actual Study Start Date : May 1, 2020
Estimated Primary Completion Date : October 15, 2020
Estimated Study Completion Date : May 15, 2021

Arm Intervention/treatment
Experimental: plasma-hyperimmune
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
patients will receive this as add on therapy

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

Active Comparator: standard therapy
enrolled patients (n=200) with severe Covid-19 infection will receive a treatment with the standard therapy
Drug: standard therapy
patients will receive only standard therapy for Covid-19 infection




Primary Outcome Measures :
  1. decrease in mortality [ Time Frame: 30 days ]
    Statistically significant reduction (P <0.05) of mortality in the group of patients treated with hyperimmune plasma vs patients treated with standard therapy.


Secondary Outcome Measures :
  1. lymphocytes [ Time Frame: 7 and 14 days ]
    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.

  2. PCR levels vs control [ Time Frame: 7 and 14 days ]
    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)

  3. PCR levels vs before treatment [ Time Frame: 7 and 14 days ]
    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

  4. AB levels and clinical improvement [ Time Frame: 30 days ]
    Significant Correlation (P<0.05) between hyperimmune plasma antibody levels and clinical improvement time (expressed in days)

  5. Inflammatory cytokines vs controls [ Time Frame: 7 and 14 days ]
    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)

  6. Inflammatory cytokines vs before treatment [ Time Frame: 7 and 14 days ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04385043


Contacts
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Contact: Gabriella Talarico, MD 0961883111 trasfusionale@aocz.it

Locations
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Italy
Azienda Ospedaliera Policlinico Mater Domini Recruiting
Catanzaro, Italy, 88100
Contact: Federico Longhini, MD    0961712111    longhini@unicz.it   
Sub-Investigator: Carlo Torti, MD         
Sub-Investigator: Giovanni Matera, MD         
Azienda Ospedaliera Pugliese Ciaccio Catanzaro Recruiting
Catanzaro, Italy, 88100
Contact: Andrea Dominijanni, MD    0961883111    trasfusionale@aocz.it   
Sub-Investigator: Pasquale Minchella, MD         
Sub-Investigator: Lucio Cosco, MD         
Sub-Investigator: Maria Laura Guzzo, MD         
Sub-Investigator: Piero Gangemi, MD         
Azienda Ospedaliera Annunziata Recruiting
Cosenza, Italy, 87100
Contact: Francesco Zinno, MD    0984 6811    f.zinno@aocs.it   
Azienda Sanitaria Provinciale Recruiting
Crotone, Italy, 88900
Contact: Patrizia Leonardo, MD    0962924471    centro.trasfusionale@asp.crotone.it   
Azienda Ospedaliera Bianchi Melacrino Morelli Recruiting
Reggio Calabria, Italy, 89133
Contact: Alfonso Trimarchi, MD    0965 730011    atrimarchi@aorc.it   
Azienda Sanitaria Provinciale Recruiting
Vibo Valentia, Italy, 89900
Contact: Paola Grandini, MD    0963-962111    trasfusionale@aspvv.it   
Sponsors and Collaborators
University of Catanzaro
Azienda Ospedaliera Policlinico "Mater Domini"
Azienda Sanitaria Provinciale Di Catanzaro
Annunziata Hospital, Cosenza, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli
Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Luca Gallelli, MD, University of Catanzaro
ClinicalTrials.gov Identifier: NCT04385043    
Other Study ID Numbers: Covid-19 convalescent plasma
First Posted: May 12, 2020    Key Record Dates
Last Update Posted: May 12, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Luca Gallelli, University of Catanzaro:
severe Covid-19
severe coronavirus-2
plasma hyperimmune
convalescent plasma
Additional relevant MeSH terms:
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Infection