Pneumonia, Ventilator-AssociatedNCT04346589
Convalescent Antibodies Infusion in Critically Ill COVID 19 Patients
A study testing Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients in people with Pneumonia, Ventilator-Associated and Coronavirus Infection, run by A.O. Ospedale Papa Giovanni XXIII at 5 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumonia, Ventilator-Associated, Coronavirus Infection
- What is being tested?
- Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 5 sitesItaly
- Study dates
- 15 Apr 2020to 27 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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
Who cannot join
- >48 hour mechanical ventilation
- Patient being treated with other anti-COVID-19 experimental treatments
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Italy5 sites
ASST HPG23 - Unit of Nephrology
Bergamo, 24100
ASST Papa Giovanni XXIII - Microbiology and Virology Unit
Bergamo, 24100
Asst Pg23 - S.I.M.T
Bergamo, 24100
ASST-PG23 - Intensive Care Unit
Bergamo, 24100
IRFMN - Clinical Research Center for Rare Diseases
Ranica, BG, 24020
About this study
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)
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.
Read more
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.
- Being tested
- Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients
- Keywords
- Pneumonia COVID 19 ventilator-dependent, COVID19, Double-filtration plasmapheresis, Convalescent antibodies
- Medical subject headings
- Pneumonia, Ventilator-Associated, Coronavirus Infections, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patientsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Antibodies (immunoglobulins) infusion | Experimental | Anti-coronavirus antibodies obtained with double-filtration plasmapheresis (DFPP )from convalescent patients. Receives: Biological: Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of mechanical ventilation days.
Measured: Through study completion, an average of 6 months.
Secondary outcomes (9)
Survival
Measured: Through study completion, an average of 6 months.
Shift to Continuous Positive Airway Pressure (CPAP) ventilation
Measured: Through study completion, an average of 6 months.
Referral to a sub-intensive care unit or discharge
Measured: Through study completion, an average of 6 months.
Viral titer
Measured: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Anti COVID 19 IgG antibodies
Measured: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Anti COVID 19 IgM antibodies
Measured: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
C5a concentration
Marker of complement activation in plasma.
Measured: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
C3a concentration
Marker of complement activation in plasma.
Measured: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Serum C5b-9 concentration
Marker of complement activation in plasma.
Measured: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
- Study start15 Apr 2020
- Primary completion17 Feb 2021
- Study completion27 Oct 2022
Why it stopped: The study was closed prematurely because the hyperimmune plasma have expired
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pneumonia, Ventilator-AssociatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- A.O. Ospedale Papa Giovanni XXIII
- Sponsor type
- University, hospital or other
- Collaborators
- Aferetica - Italy (BO)
- Responsible party
- Principal investigator, Piero Luigi Ruggenenti, A.O. Ospedale Papa Giovanni XXIII
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04346589
- Sponsor's protocol ID
- DFPP COVID 19
- Status last verified
- Mar 2023
- First submitted
- 9 Apr 2020
- Last updated
- 23 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Curto D, Tomatis F, Gastoldi S, Galbusera M, Noris M, Raimondi F, Lorini FL, Falanga A, Marchetti M, Remuzzi G, Ruggenenti P. Case Report: Effects of Anti-SARS-CoV-2 Convalescent Antibodies Obtained With Double Filtration Plasmapheresis. Front Immunol. 2021 Jun 30;12:711915. doi: 10.3389/fimmu.2021.711915. eCollection 2021.
PubMed 34276706
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04346589
- Acronym / sponsor ID
- DFPP COVID 19
- Keywords
- Pneumonia COVID 19 ventilator-dependent, COVID19, Double-filtration plasmapheresis, Convalescent antibodies
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was closed prematurely because the hyperimmune plasma have expired
- Enrolment
- 9 participants (actual)
- Lead sponsor
- A.O. Ospedale Papa Giovanni XXIIIUniversity, hospital or other
- Collaborators
- Aferetica - Italy (BO)
- Study start
- 15 Apr 2020 (actual)
- Primary completion
- 17 Feb 2021 (actual)
- Study completion
- 27 Oct 2022 (actual)
- First posted
- 15 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Antibodies (immunoglobulins) infusion | Experimental | Biological: Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patientsAnti-coronavirus antibodies obtained with double-filtration plasmapheresis (DFPP )from convalescent patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (2 listed)
- >48 hour mechanical ventilation
- Patient being treated with other anti-COVID-19 experimental treatments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patientsAntibodies 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. | Biological | Antibodies (immunoglobulins) infusion |
Primary outcome
Number of mechanical ventilation days.
Time frame: Through study completion, an average of 6 months.
9 secondary outcomes
Survival
Time frame: Through study completion, an average of 6 months.
Shift to Continuous Positive Airway Pressure (CPAP) ventilation
Time frame: Through study completion, an average of 6 months.
Referral to a sub-intensive care unit or discharge
Time frame: Through study completion, an average of 6 months.
Viral titer
Time frame: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Anti COVID 19 IgG antibodies
Time frame: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Anti COVID 19 IgM antibodies
Time frame: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
C5a concentration
Time frame: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
C3a concentration
Time frame: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Serum C5b-9 concentration
Time frame: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
Results and safety
The study was stopped early (reason given: The study was closed prematurely because the hyperimmune plasma have expired). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2023.
- Results publication: PubMed 34276706Curto D, Tomatis F, Gastoldi S, Galbusera M, Noris M, Raimondi F, Lorini FL, Falanga A, Marchetti M, Remuzzi G, Ruggenenti P. Case Report: Effects of Anti-SARS-CoV-2 Convalescent Antibodies Obtained With Double Filtration Plasmapheresis. Front Immunol. 2021 Jun 30;12:711915. doi: 10.3389/fimmu.2021.711915. eCollection 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients in people with Pneumonia, Ventilator-Associated and Coronavirus Infection, run by A.O. Ospedale Papa Giovanni XXIII at 5 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The study was closed prematurely because the hyperimmune plasma have expired). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of mechanical ventilation days. (time frame: Through study completion, an average of 6 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04346589, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2023.