Plasma Therapy of COVID-19 in Severely Ill Patients

NCT04359810 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAS9924
• Study Type: interventional
• Target: 223
• Locations: 2 countries
• Sites: 4

Brief Summary

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).

Conditions

SARS-CoV-2 Infection

Keywords

COVID-19; COVID; Coronavirus; Convalescent plasma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status

  Compare the day 28 severity outcome amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups using a 7-point ordinal scale of clinical status. Seven-point ordinal scale for clinical assessment ranges from 1 and 2: Not hospitalized 3: Hospitalized, not requiring supplemental oxygen 4: Hospitalized, requiring supplemental oxygen 5: Hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation 6: Hospitalized, requiring IMV, ECMO, or both 7: Dead Higher number means worse outcome

  Up to 28 days

Secondary Outcomes (8)

• Proportion of SARS-CoV-2 PCR Positivity

  Up to 14 days

• Levels of SARS-CoV-2 RNA

  Up to 14 days

• Duration of Need for Supplemental Oxygen

  Up to 28 days

• Duration of Hospitalization

  Up to 28 days

• 28-day Mortality

  Up to 28 days

Study Arms (2)

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

EXPERIMENTAL

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

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

Non-convalescent Plasma (control plasma)

ACTIVE COMPARATOR

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

Biological: Non-convalescent Plasma (control plasma)

Interventions

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

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

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

Non-convalescent Plasma (control plasma) BIOLOGICAL

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

Non-convalescent Plasma (control plasma)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Use of remdesivir as treatment for COVID-19 is permitted.

Sponsors & Collaborators

• Max O'Donnell: lead
• New York Blood Center: collaborator
• Amazon, Inc.: collaborator

Study Sites (4)

Columbia University Irving Medical Center/NYP

New York, New York, 10032, United States

Location

Hospital Federal dos Servidores do Estado

Rio de Janeiro, Brazil

Location

Hospital Geral de Nova Iguaçu

Rio de Janeiro, Brazil

Location

Instituto Nacional de Infectologia Evandro Chagas

Rio de Janeiro, Brazil

Location

Related Publications (12)

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  PMID: 27532807 BACKGROUND

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• 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.

  PMID: 7985997 BACKGROUND

• 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.

  PMID: 15616839 BACKGROUND

• 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.

  PMID: 32492084 BACKGROUND

• 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.

  PMID: 32219428 BACKGROUND

• 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.

  PMID: 32934372 BACKGROUND

• 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.

  PMID: 37162745 DERIVED

• 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.

  PMID: 36734509 DERIVED

• 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.

  PMID: 34013969 DERIVED

• 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.

  PMID: 33974559 DERIVED

• 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.

  PMID: 32513308 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Max O'Donnell, MD
• Organization: Columbia University Irving Medical Center

mo2130@columbia.edu

212-305-5794

Study Officials

• Max O'Donnell, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Florence Irving Associate Professor of Medicine and Epidemiology

Model Details: 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).

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: April 21, 2020
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (1); BR (3)