VA CoronavirUs Research and Efficacy Studies-1

NCT04539275 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: COVID19-8900-22
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 24

Brief Summary

The purpose of this study is to determine if treatment with convalescent plasma improves the clinical outcomes of Veterans who are hospitalized and require supplemental oxygen due to COVID-19.

Conditions

COVID-19

Keywords

2019 novel coronavirus disease; COVID-19 pandemic; COVID-19 virus infection; COVID-19 virus disease; Respiratory failure; Pneumonia, viral / therapy; Blood Component Transfusion; Severity of Illness Index; Survival Analysis; Treatment Outcome; Prospective Study; Humans; Adults; Male; Female; convalescent plasma; SARS CoV-2; COVID-19 convalescent plasma

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death

  Respiratory failure is defined as requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.

  Day 1 through Day 28

Secondary Outcomes (14)

• Time (in Days) to Recovery

  Day 1 through Day 28

• Time (in Days) to Death or Respiratory Failure

  Day 1 through Day 28

• Proportion of Patients Who Died From Any Cause, Had Respiratory Failure, or Required Humidified Heated High-flow Nasal Cannula (HHHFNC) at >= 15 Lpm

  Day 1 through Day 28

• Time (in Days) to Death, Respiratory Failure, or HHHFNC at >= 15 Lpm

  Day 1 through Day 28

• Number of Participants With 28-day All-cause Mortality

  Day 1 through Day 28

Study Arms (2)

Convalescent Plasma

EXPERIMENTAL

The study intervention consists of intravenous administration of 200-500 mL of convalescent plasma administered in two equally divided doses, less than 12 hours apart.

Drug: Convalescent Plasma

Masked Saline Placebo

PLACEBO COMPARATOR

The study intervention consists of intravenous administration of 200-500 mL of 0.9% saline administered in two equally divided doses, less than 12 hours apart.

Other: Masked Saline Placebo

Interventions

Convalescent Plasma DRUG

Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection.

Also known as: COVID-19 Convalescent Plasma (CCP)

Convalescent Plasma

Masked Saline Placebo OTHER

0.9% saline solution will be used as the Masked Saline Placebo

Also known as: Normal Saline (NS)

Masked Saline Placebo

Eligibility Criteria

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

You may qualify if:

• Veterans must meet all of the following criteria to be eligible to participate:
• Admitted to a participating VA clinical site with symptoms suggestive of SARS-CoV-2 infection.
• Participant (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
• Participant (or legally authorized representative) understands and agrees to comply with planned study procedures.
• Veteran 18 years of age at time of screening.
• Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or antigen test, as documented by either of the following:
• (1)Reverse Transcription polymerase chain reaction (RT-PCR) or antigen positive (nasopharyngeal, oropharyngeal, saliva, lower respiratory) in sample collected 72 hours prior to screening; (2)RT-PCR or antigen positive in sample collected \> 72 hours but 168 hours (i.e. 7 days) prior to screening, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking \> 24 hours, etc.), AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
• Requiring oxygen by nasal cannula or by face-mask as a new treatment (or if previously on home oxygen, at a liter flow at least 2 Lpm greater than home prescription), but not on humidified heated high-flow nasal cannula (HHHFNC) at 15 Lpm.
• Can be randomized within 72 hours of hospital admission. 8.Agrees not to participate in another therapeutic clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29 without approval from the investigator(s). Taking part in other research studies, including those unrelated to SARS-CoV-2, without first discussing it with the investigators of this study may invalidate the results of this study, as well as that of the other study.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Respiratory failure requiring mechanical ventilation, non-invasive ventilation including continuous positive airway pressure (CPAP) (for an indication other than previously diagnosed sleep apnea and maintained on outpatient settings), or extra-corporeal membrane oxygenation or anticipated to require any of those treatments or to die within 24 hours.
• Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 hours.
• History of previous transfusion reaction.
• Previously documented serum immunoglobulin A (IgA) deficiency (\<7 mg/dL)
• Documented to have received convalescent plasma in the last 60 days.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (24)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233, United States

Location

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, 85012, United States

Location

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045, United States

Location

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, 32608, United States

Location

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, 32803, United States

Location

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, 33612, United States

Location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

Location

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-5000, United States

Location

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

Location

John D. Dingell VA Medical Center, Detroit, MI

Detroit, Michigan, 48201, United States

Location

VA Southern Nevada Healthcare System, North Las Vegas, NV

North Las Vegas, Nevada, 89086, United States

Location

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468, United States

Location

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

Location

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, 73104, United States

Location

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

Location

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799, United States

Location

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, 78229, United States

Location

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148, United States

Location

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249, United States

Location

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705, United States

Location

VA Caribbean Healthcare System, San Juan, PR

San Juan, 00921, Puerto Rico

Location

Related Publications (3)

• Janoff EN, Shih MC, Donskey C, Belitskaya-Levy I, Brau N, Rodriguez-Barradas MC, Chan E, Zimmerman P, Miller EK, Vaughan LB, Daniel Markley J, Goldberg AM, Sriram P, Anzueto A, Uyeda L, Zehm L, Wills A, Hutchinson C, Jones L, Peterson D, Ringer RJ, Dumont L, Gleason T, Bonomo RA, Curtis JL, Brown ST; CURES-1 Trials Consortium. Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1). J Med Virol. 2025 May;97(5):e70349. doi: 10.1002/jmv.70349.

  PMID: 40400480 DERIVED

• Janoff EN, Brown ST, Belitskaya-Levy I, Curtis JL, Bonomo RA, Miller EK, Goldberg AM, Zehm L, Wills A, Hutchinson C, Dumont LJ, Gleason T, Shih MC; ADD Caitlin MS in CCTC website. Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise. Contemp Clin Trials Commun. 2023 Jul 17;35:101190. doi: 10.1016/j.conctc.2023.101190. eCollection 2023 Oct.

  PMID: 37560085 DERIVED

• Miller EK, Goldberg AM, Janoff EN, Brown ST, Curtis JL, Bonomo RA, Shih MC, Gleason TC. Designing and implementing methodology for double-blind, placebo-controlled clinical trials using blood products within the Department of Veterans Affairs. Clin Trials. 2022 Apr;19(2):137-145. doi: 10.1177/17407745211069703. Epub 2022 Mar 1.

  PMID: 35229691 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Insufficiency; Pneumonia

Interventions

COVID-19 Serotherapy; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Lisa Zehm, Project Manager
• Organization: Palo Alto Cooperative Studies Program Coordinating Center

lisa.zehm@va.gov

(650)493-5000

Study Officials

• Edward N. Janoff, MD

  Rocky Mountain Regional VA Medical Center, Aurora, CO

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The participants, site investigators, clinical prescribers, site coordinators, and most other individuals involved in this study will be blinded to the treatment assignment. Furthermore, the blind will not routinely be broken in order to select post-study, pharmacologic treatment for SARS-CoV-2 infection administered by clinical healthcare providers.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: There are two study treatment arms: convalescent plasma versus saline. Participants will be randomized in 1:1 ratio to these two arms.

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 4, 2020
• Study Start: November 16, 2020
• Primary Completion: June 30, 2021
• Study Completion: September 30, 2021
• Last Updated: September 23, 2022
• Results First Posted: September 10, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (23)