Official Title
A Pilot Study to Explore the Efficacy and Safety of Rescue Theraphy With Antibodies From Convalescent Patients Obtained With Double -Filtration Plasmapheresis (DFPP) and Infused in Critically Ill Ventilated Patients With Coronavirus Disease 2019 (COVID-19)
Brief Summary

The 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID 19), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite any attempted treatment.. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Plasma-exchange is expensive and requires large volumes of substitution fluid. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The aforementioned limitations of plasma therapy can be overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP).DFPP is a modality of plasma purification that performs an initial plasma separation from blood, and the subsequent separation of specific molecules, on the basis of their specific molecular weight (cut-off), by using a fractionation filter. The Fractionation Filter 2A20, because of its membrane sieving cut-off, retains larger molecules and returns plasma along with smaller molecules to the circulation, including the major part of the albumin. The selection of the membrane 2A20 is related to the appropriate Sieving Coefficient for IgG that allows to efficiently collect antibodies from patients which are recovered from COVID-19, with negligible fluid losses and limited removal of albumin. The total amount of antibodies obtained during one DFPP session exceeds by three to four times the total amount provided to recipients with one unit of plasma obtained during one plasma-exchange session from one COVID-19 convalescent donor. This should result in more effective viral inhibition and larger benefit for the patient achieved with one unit of enriched immunoglobulin solution obtained with DFPP than with one unit of plasma obtained with plasma exchange. These observations provide the background for a pilot study aimed to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for critically ill patients with severe coronavirus (COVID-19) pneumonia requiring mechanical ventilation.

Terminated
Pneumonia, Ventilator-Associated
Coronavirus Infection

Biological: Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients

Antibodies obtained from consenting convalescent donors will be administered to ten consecutive patients who fulfill the inclusion criteria . Convalescent antibodies will be obtained with one DFPP procedure from consenting donors and infused in one critically ill, ventilated patient with COVID 19 pneumonia.

Eligibility Criteria

Inclusion Criteria:

Plasma Ig Donors

- Adult (>18 and <65-yr-old) men and women

- Convalescent donor who recovered from COVID 19 from at least 14 days according to the
clinical and laboratory criteria defined by the Consiglio Superiore di Sanità on
February 20, 2019 ("The recovered patient is the one who resolves the symptoms of
COVID-19 infection and who is negative in two consecutive tests for the search for
SARS-Cov-2, performed 24 hours apart") with the exceptions mentioned in the attached
derogation (that is "no upper age limit to donation provided there are no clinical
contraindications to the procedure and independent of documented evidence of two
negative tests for SARS-Cov 2 naso-faringeal contamination")

- Male or female donor; if female only if nulliparous; in both cases with a negative
history of blood component transfusions

- Careful clinical evaluation of the patient-donor with particular reference to the
criteria established by current legislation to protect the health of the donor who
donates by apheresis

- Presence of adequate levels of neutralizing anti-SARS-COV-2 antibodies;

- Biological qualification test negative defined by current indications (performed at
SIMT of HPG23)

- Test negative for: HAV RNA, HEV RNA, PVB19 DNA (performed at HPG23)

- Informed consent

Recipients

- Adult (>18-yr-old) men and women

- COVID-19 pneumonia diagnosed by standard criteria

- Need of ventilator support

- Informed consent for participation in the study (critically ill patients will be
unable to provide consent. Consent will be oral if a written consent will be
impossible. If the subject is incapable of giving an informed consent and an
authorized representative is not available without a delay that would, in the opinion
of the Investigator, compromise the potential life-saving effect of the treatment this
can be administered without consent. Consent to remain in the research should be
sought as soon as the conditions of the patient will allow it).

- <48 hours of mechanical ventilation

Exclusion Criteria:

- >48 hour mechanical ventilation

- Patient being treated with other anti-COVID-19 experimental treatments

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Italy
Locations

IRFMN - Clinical Research Center for Rare Diseases
Ranica, BG, Italy

ASST HPG23 - Unit of Nephrology
Bergamo, Italy

ASST Papa Giovanni XXIII - Microbiology and Virology Unit
Bergamo, Italy

Asst Pg23 - S.I.M.T
Bergamo, Italy

ASST-PG23 - Intensive Care Unit
Bergamo, Italy

Aferetica - Italy (BO)
NCT Number
Keywords
Pneumonia COVID 19 ventilator-dependent
COVID19
Double-filtration plasmapheresis
Convalescent antibodies
MeSH Terms
COVID-19
Pneumonia
Coronavirus Infections
Pneumonia, Ventilator-Associated
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous