Plasma Therapy of COVID-19 in Severely Ill Patients

SARS-CoV-2 Infection Clinical Trial

Official title:

A Phase 2, Multi-Center, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Human Anti-SARS-CoV-2 Convalescent Plasma in Severely Ill Adults With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04359810
• Other study ID #: AAAS9924
• Status: Completed
• Phase: Phase 2
• Start date: April 21, 2020
• Est. completion date: December 30, 2020

Study information

• Verified date: May 2021
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: December 30, 2020
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• SARS-CoV-2 Infection

Intervention

Biological:
• Convalescent Plasma (anti-SARS-CoV-2 plasma)
Convalescent Plasma that contains antibody titers against SARS-CoV-2
• Non-convalescent Plasma (control plasma)
Non-convalescent plasma (does not contain antibody titers against SARS-CoV-2)

Locations

Country	Name	City	State
Brazil	Hospital Federal dos Servidores do Estado	Rio De Janeiro
Brazil	Hospital Geral de Nova Iguaçu	Rio De Janeiro
Brazil	Instituto Nacional de Infectologia Evandro Chagas	Rio De Janeiro
United States	Columbia University Irving Medical Center/NYP	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Max O'Donnell	Amazon.com, Inc., New York Blood Center

Countries where clinical trial is conducted

United States,  Brazil, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Erratum in: JAMA. 2020 Aug 4;324(5):519. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Day 28 severity outcome	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.	Up to 28 days
Secondary	Proportion of SARS-CoV-2 PCR Positivity	Compare the proportion and duration of SARS-CoV-2 PCR positivity (via RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups at days 0, 7, and 14.	Up to 14 days
Secondary	Levels of SARS-CoV-2 RNA	Compare levels of SARS-CoV-2 RNA amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups at days 0, 7, and 14.	Up to 14 days
Secondary	Duration of Need for Supplemental Oxygen	Compare duration of need for supplemental oxygen and/or mechanical ventilation amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.	Up to 28 days
Secondary	Duration of Hospitalization	Compare duration of hospitalization amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.	Up to 28 days
Secondary	In-hospital and 28-day mortality	Compare in-hospital and 28-day mortality amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.	Up to 28 days
Secondary	Time-to-clinical improvement in-hospital	Compare time-to-clinical improvement in-hospital amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups, defined as the time to either an improvement of one point on a 7-point ordinal scale of clinical status or alive discharge from the hospital, whichever comes first.	Up to 28 days
Secondary	Host genetic differences at day 0	To assess for host genetic differences at Day 0 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.	Day 0
Secondary	Host transcriptomic differences at days 0,7,14	To assess for host transcriptomic differences at Day 0,7,14 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.	Up to 14 days