Hyperimmune Plasma for Critical Patients With COVID-19 (COV19-PLASMA)

• ClinicalTrials.gov Identifier: NCT04321421
• Recruitment Status: Completed
• First Posted: March 25, 2020
• Last Update Posted: May 28, 2020
• Sponsor: Foundation IRCCS San Matteo Hospital
• Collaborator: OSPEDALE CARLO POMA ASST MANTOVA
• Information provided by (Responsible Party): Cesare Perotti, Foundation IRCCS San Matteo Hospital

Tracking Information

• First Submitted Date: March 23, 2020
• First Posted Date: March 25, 2020
• Last Update Posted Date: May 28, 2020
• Actual Study Start Date: March 17, 2020
• Actual Primary Completion Date: April 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2020)

death [ Time Frame: within 7 days ]

death from any cause

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 23, 2020)

• time to extubation [ Time Frame: within 7 days ]
  days since intubation
• length of intensive care unit stay [ Time Frame: within 7 days ]
  days from entry to exit from ICU
• time to CPAP weaning [ Time Frame: within 7 days ]
  days since CPAP initiation
• viral load [ Time Frame: at days 1, 3 and 7 ]
  naso-pharyngeal swab, sputum and BAL
• immune response [ Time Frame: at days 1, 3 and 7 ]
  neutralizing title

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hyperimmune Plasma for Critical Patients With COVID-19
• Official Title: Plasma From Donors Recovered From New Coronavirus 2019 As Therapy For Critical Patients With Covid-19
• Brief Summary: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become pandemic. To date, no specific treatment has been proven to be effective. Promising results were obtained in China using Hyperimmune plasma from patients recovered from the disease.The investigators plan to treat critical Covid-19 patients with hyperimmune plasma.

Detailed Description

Apheresis from recovered donors will be performed with a cell separator device , with 500-600 mL of plasma obtained from each donor. Donors are males, age 18 yrs or more, evaluated for transmissible diseases according to the italian law. Adjunctive tests will be for hepatitis A virus, hepatitis E virus and Parvovirus B-19. All donors will be tested for the Covid-19 neutralizing title. Each plasma bag obtained from plasmapheresis will be immediately divided in two units and frozen according to the national standards and stored separately.

Based on experience published in literature 250-300 mL of convalescent plasma will be used to treat each of the recruited patients at most 3 times over 5 days.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Longitudinal assessment of COVID-19 patients treated with hyperimmune plasma

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: COVID-19

Intervention

Other: hyperimmune plasma

administration of hyperimmune plasma at day 1 and based on clinical response on day 3 and 5

Study Arms

Experimental: treated

treated with hyperimmune plasma

Intervention: Other: hyperimmune plasma

Publications *

• 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.
• WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. 2020. https://www.who. int/docs/default-source/coronaviruse/clinical-management-of-novel-cov. pdf (accessed Feb 20, 2020).
• Lai ST. Treatment of severe acute respiratory syndrome. Eur J Clin Microbiol Infect Dis. 2005 Sep;24(9):583-91. Review.
• WHO. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks. 2014. http://apps.who.int/iris/rest/ bitstreams/604045/retrieve (accessed Feb 20, 2020).
• 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. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.
• Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
• Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31.
• Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5:CD013600. doi: 10.1002/14651858.CD013600.pub4.
• Chai KL, Valk SJ, Piechotta V, Kimber C, Monsef I, Doree C, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2020 Oct 12;10:CD013600. doi: 10.1002/14651858.CD013600.pub3. Update in: Cochrane Database Syst Rev. 2021 May 20;5:CD013600.
• Piechotta V, Chai KL, Valk SJ, Doree C, Monsef I, Wood EM, Lamikanra A, Kimber C, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2020 Jul 10;7:CD013600. doi: 10.1002/14651858.CD013600.pub2. Update in: Cochrane Database Syst Rev. 2020 Oct 12;10:CD013600.
• Perotti C, Del Fante C, Baldanti F, Franchini M, Percivalle E, Vecchio Nepita E, Seminari E, De Silvestri A, Bruno R, Klersy C. Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol. Intern Emerg Med. 2020 Aug;15(5):819-824. doi: 10.1007/s11739-020-02384-2. Epub 2020 May 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 23, 2020): 49
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 7, 2020
• Actual Primary Completion Date: April 28, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age >=18 yrs
• positive for reverse transcription polymerase chain reaction (RT-PCR) severe acute respiratory syndrome (SARS)-CoV-2
• Acute respiratory distress syndrome (ARDS) moderate to severe, according to Berlin definition, lasting less than10 days
• Polymerase chain reaction (PCR) increased by 3.5 with respect to baseline or >1.8 mg/dl
• need for mechanical ventilation or continuous positive airway pressure (CPAP)
• signed informed consent unless unfeasible for the critical condition

Exclusion Criteria:

• Moderate to severe ARDS lasting more than 10 days
• proven hypersensitivity or allergic reaction to hemoderivatives or immunoglobulins
• consent denied

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04321421
• Other Study ID Numbers: IRCCSSanMatteoH
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: will be decided

• Current Responsible Party: Cesare Perotti, Foundation IRCCS San Matteo Hospital
• Original Responsible Party: Cesare Perotti, Foundation IRCCS San Matteo Hospital, Medical Doctor
• Current Study Sponsor: Foundation IRCCS San Matteo Hospital
• Original Study Sponsor: Same as current
• Collaborators: OSPEDALE CARLO POMA ASST MANTOVA

Investigators

• Principal Investigator: Cesare Perotti, MD; Foundation IRCCS San Matteo Hospital

• PRS Account: Foundation IRCCS San Matteo Hospital
• Verification Date: May 2020