Plasma Therapy of COVID-19 in Severely Ill Patients

NCT ID: NCT04359810

Last Updated: 2024-09-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

223 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-21

Study Completion Date

2020-12-30

Brief Summary

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This randomized blinded multi-center phase 2 trial will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma among adults with severe COVID-19. Adults ≥18 years of age may participate. A total of 219 eligible subjects will be randomized in a 2:1 ratio to receive either high-titer anti-SARS-CoV-2 plasma or non-convalescent fresh frozen plasma (control plasma).

Detailed Description

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There are few effective therapies for coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Exposure to viruses results in an adaptive immune response that commonly include antibodies with neutralization activity. Plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Argentine hemorrhagic fever, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS-CoV). Small clinical trials and observational studies of CP therapy in patients with COVID-19 have suggested a possible clinical benefit.

Conditions

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SARS-CoV-2 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A total of 219 eligible subjects will be randomized in a 2:1 ratio to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or non-convalescent fresh frozen plasma (control plasma).
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Convalescent Plasma (anti-SARS-CoV-2 plasma)

Convalescent plasma (1 unit; \~200-250 mL) collected from a volunteer who recovered from COVID-19 disease

Group Type EXPERIMENTAL

Convalescent Plasma (anti-SARS-CoV-2 plasma)

Intervention Type BIOLOGICAL

Convalescent Plasma that contains antibody titers against SARS-CoV-2

Non-convalescent Plasma (control plasma)

Non-convalescent plasma (1 unit; \~200-250 mL) of standard plasma collected prior to December 2019

Group Type ACTIVE_COMPARATOR

Non-convalescent Plasma (control plasma)

Intervention Type BIOLOGICAL

Non-convalescent plasma (does not contain antibody titers against SARS-CoV-2)

Interventions

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Convalescent Plasma (anti-SARS-CoV-2 plasma)

Convalescent Plasma that contains antibody titers against SARS-CoV-2

Intervention Type BIOLOGICAL

Non-convalescent Plasma (control plasma)

Non-convalescent plasma (does not contain antibody titers against SARS-CoV-2)

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Willing and able to provide written informed consent prior to performing study procedures or have a legally authorized representative available to do so.
* Age ≥18 years
* Evidence of SARS-CoV-2 infection by PCR test of naso-/oro-pharyngeal swab or tracheal aspirate sample within 14 days of randomization
* Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen, non-invasive or invasive mechanical ventilation at screening
* Evidence of infiltrates on chest radiography
* Females of childbearing age and males, must be willing to practice an effective contraceptive method or remain abstinent during the study period.

Exclusion Criteria

* Participation in another clinical trial of anti-viral agent(s) for COVID-19
* Receipt of any anti-viral agent(s) with possible activity against SARS-CoV-2 \<24 hours prior to study drug administration \[1\]
* Mechanically ventilated (including veno-venous (VV)-ECMO) ≥ 5 days
* Severe multi-organ failure
* History of prior reactions to transfusion blood products meeting definitive case definition criteria, at least severe severity, and probable or definite imputability per National Healthcare Safety Network (NHSN)/Centers for Disease Control and Prevention (CDC) criteria
* Known Immunoglobulin A (IgA) deficiency
* Females who are pregnant

1. Use of remdesivir as treatment for COVID-19 is permitted.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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New York Blood Center

OTHER

Sponsor Role collaborator

Amazon, Inc.

INDUSTRY

Sponsor Role collaborator

Max O'Donnell

OTHER

Sponsor Role lead

Responsible Party

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Max O'Donnell

Florence Irving Associate Professor of Medicine and Epidemiology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Max O'Donnell, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Columbia University Irving Medical Center/NYP

New York, New York, United States

Site Status

Hospital Federal dos Servidores do Estado

Rio de Janeiro, , Brazil

Site Status

Hospital Geral de Nova Iguaçu

Rio de Janeiro, , Brazil

Site Status

Instituto Nacional de Infectologia Evandro Chagas

Rio de Janeiro, , Brazil

Site Status

Countries

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United States Brazil

References

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Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis. 2016 Sep;22(9):1554-61. doi: 10.3201/eid2209.151164.

Reference Type BACKGROUND
PMID: 27532807 (View on PubMed)

Austin PC, Fine JP. Practical recommendations for reporting Fine-Gray model analyses for competing risk data. Stat Med. 2017 Nov 30;36(27):4391-4400. doi: 10.1002/sim.7501. Epub 2017 Sep 15.

Reference Type BACKGROUND
PMID: 28913837 (View on PubMed)

Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.

Reference Type BACKGROUND
PMID: 7985997 (View on PubMed)

Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.

Reference Type BACKGROUND
PMID: 15616839 (View on PubMed)

Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, Hu C, Tao C, Yang R, Wang J, Yu Y, Guo Y, Wu X, Xu Z, Zeng L, Xiong N, Chen L, Wang J, Man N, Liu Y, Xu H, Deng E, Zhang X, Li C, Wang C, Su S, Zhang L, Wang J, Wu Y, Liu Z. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. 2020 Aug 4;324(5):460-470. doi: 10.1001/jama.2020.10044.

Reference Type BACKGROUND
PMID: 32492084 (View on PubMed)

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.

Reference Type BACKGROUND
PMID: 32219428 (View on PubMed)

Liu STH, Lin HM, Baine I, Wajnberg A, Gumprecht JP, Rahman F, Rodriguez D, Tandon P, Bassily-Marcus A, Bander J, Sanky C, Dupper A, Zheng A, Nguyen FT, Amanat F, Stadlbauer D, Altman DR, Chen BK, Krammer F, Mendu DR, Firpo-Betancourt A, Levin MA, Bagiella E, Casadevall A, Cordon-Cardo C, Jhang JS, Arinsburg SA, Reich DL, Aberg JA, Bouvier NM. Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study. Nat Med. 2020 Nov;26(11):1708-1713. doi: 10.1038/s41591-020-1088-9. Epub 2020 Sep 15.

Reference Type BACKGROUND
PMID: 32934372 (View on PubMed)

Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6.

Reference Type DERIVED
PMID: 37162745 (View on PubMed)

Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 Feb 1;2(2):CD013600. doi: 10.1002/14651858.CD013600.pub5.

Reference Type DERIVED
PMID: 36734509 (View on PubMed)

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(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.

Reference Type DERIVED
PMID: 34013969 (View on PubMed)

O'Donnell MR, Grinsztejn B, Cummings MJ, Justman JE, Lamb MR, Eckhardt CM, Philip NM, Cheung YK, Gupta V, Joao E, Pilotto JH, Diniz MP, Cardoso SW, Abrams D, Rajagopalan KN, Borden SE, Wolf A, Sidi LC, Vizzoni A, Veloso VG, Bitan ZC, Scotto DE, Meyer BJ, Jacobson SD, Kantor A, Mishra N, Chauhan LV, Stone EF, Dei Zotti F, La Carpia F, Hudson KE, Ferrara SA, Schwartz J, Stotler BA, Lin WW, Wontakal SN, Shaz B, Briese T, Hod EA, Spitalnik SL, Eisenberger A, Lipkin WI. A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19. J Clin Invest. 2021 Jul 1;131(13):e150646. doi: 10.1172/JCI150646.

Reference Type DERIVED
PMID: 33974559 (View on PubMed)

Eckhardt CM, Cummings MJ, Rajagopalan KN, Borden S, Bitan ZC, Wolf A, Kantor A, Briese T, Meyer BJ, Jacobson SD, Scotto D, Mishra N, Philip NM, Stotler BA, Schwartz J, Shaz B, Spitalnik SL, Eisenberger A, Hod EA, Justman J, Cheung K, Lipkin WI, O'Donnell MR. Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Jun 8;21(1):499. doi: 10.1186/s13063-020-04422-y.

Reference Type DERIVED
PMID: 32513308 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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AAAS9924

Identifier Type: -

Identifier Source: org_study_id

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