Convalescent Plasma in Outpatients With COVID-19

NCT04355767 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: C3PO1OT2HL156812-01
• Study Type: interventional
• Target: 511
• Locations: 1 country
• Sites: 53

Brief Summary

The overarching goal of this project is to confirm or refute the role of passive immunization as a safe and efficacious therapy in preventing the progression from mild to severe/critical COVID-19 illness and to understand the immunologic kinetics of anti-SARS-CoV-2 antibodies after passive immunization.The primary objective is to determine the efficacy and safety of a single dose of convalescent plasma (CP) for preventing the progression from mild to severe COVID-19 illness. The secondary objective is to characterize the immunologic response to CP administration. This study will enroll adults presenting to the emergency department (ED) with mild, symptomatic, laboratory-confirmed COVID-19 illness, who are at high risk for progression to severe/critical illness, but who are clinically stable for outpatient management at randomization.

Conditions

Covid19

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Disease Progression (Intention-to-treat Population)

  Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

  15 days

• Number of Patients With Disease Progression (Per-protocol Population)

  Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

  15 days

Secondary Outcomes (4)

• Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization

  30 days

• Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression

  15 days

• Number of Hospital-free Days During the 30 Days Following Randomization

  30 days

• All-cause Mortality

  Assessed at 30 days

Study Arms (2)

Convalescent Plasma

EXPERIMENTAL

Participants receive 1 unit of convalescent plasma.

Biological: Convalescent Plasma

Placebo

PLACEBO COMPARATOR

Participants receive 1 unit of saline with multivitamin.

Biological: Saline

Interventions

Convalescent Plasma BIOLOGICAL

SARS-CoV-2 convalescent plasma with neutralizing SARS-CoV2 antibodies titers of ≥1:160 administered via intravenous (IV) infusion.

Convalescent Plasma

Saline BIOLOGICAL

Saline with multivitamin administered via intravenous (IV) infusion..

Placebo

Eligibility Criteria

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

You may qualify if:

• One or more symptoms of COVID-19 illness and laboratory-confirmed SARS-CoV-2 infection
• Has at least one study defined risk factor for severe COVID-19 illness
• Clinical team deems stable for outpatient management without supplemental oxygen
• CP available at the site at the time of enrollment
• Duration of symptoms ≤ 7 days at ED presentation
• Informed consent from subject

You may not qualify if:

• Age less than 18 years
• Prisoner or ward of the state
• Presumed unable to complete follow-up assessments
• Prior adverse reaction(s) from blood product transfusion
• Receipt of any blood product within the past 120 days
• Treating clinical team unwilling to administer 300 ml fluid
• Enrollment in another interventional trial for COVID-19 illness

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Strategies to Innovate EmeRgENcy Care Clinical Trials Network: collaborator
• University of Pittsburgh: collaborator
• Medical University of South Carolina: collaborator

Study Sites (53)

Chandler Regional Medical Center

Chandler, Arizona, 85224, United States

Location

Valleywise Health Medical Center

Phoenix, Arizona, 85008, United States

Location

UCSD Health La Jolla

La Jolla, California, 92037, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90211, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32608, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois Hospital

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

University of Michigan University Hospital

Ann Arbor, Michigan, 48109, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Harper University Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Sinai-Grace Hospital

Detroit, Michigan, 48235, United States

Location

Spectrum Health Hospitals Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

William Beaumont Hospital-Troy

Troy, Michigan, 48085, United States

Location

HealthPartners Methodist Hospital

Saint Louis Park, Minnesota, 55426, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Mercy St. Vincent Medical Center

Toledo, Ohio, 43608, United States

Location

Oregon Health & Science University Hospital

Portland, Oregon, 97239, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

William P. Clements Jr. University Hospital

Dallas, Texas, 75235, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States

Location

University of Utah Healthcare

Salt Lake City, Utah, 84132, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Korley FK, Durkalski-Mauldin V, Yeatts SD, Schulman K, Davenport RD, Dumont LJ, El Kassar N, Foster LD, Hah JM, Jaiswal S, Kaplan A, Lowell E, McDyer JF, Quinn J, Triulzi DJ, Van Huysen C, Stevenson VLW, Yadav K, Jones CW, Kea B, Burnett A, Reynolds JC, Greineder CF, Haas NL, Beiser DG, Silbergleit R, Barsan W, Callaway CW; SIREN-C3PO Investigators. Early Convalescent Plasma for High-Risk Outpatients with Covid-19. N Engl J Med. 2021 Nov 18;385(21):1951-1960. doi: 10.1056/NEJMoa2103784. Epub 2021 Aug 18.

  PMID: 34407339 RESULT

Related Links

• SIREN Network
• Statistical Design and Analysis Plan for Sequential Parallel-Group RCT for COVID-19 (Harrell and Lindsell, 2020)

MeSH Terms

Conditions

COVID-19

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

This study did not meet its maximum sample size of 900 participants due to a planned interim analysis that indicated that it was unlikely that there would be a difference in the rate of disease progression between the two groups if continued to the planned sample size.

Results Point of Contact

• Title: Kevin Schulman, MD
• Organization: Stanford University

kevin.schulman@stanford.edu

(650) 724-0543

Study Officials

• Clifton W Callaway, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Valerie Durkalski-Mauldin, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Frederick Korley, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Sharon Yeatts, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Robert Silbergleit, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• William Barsan, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Kevin Schulman, MD

  Stanford University

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 21, 2020
• Study Start: August 11, 2020
• Primary Completion: March 29, 2021
• Study Completion: March 29, 2021
• Last Updated: October 19, 2021
• Results First Posted: October 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available indefinitely.
• Access Criteria: Data requests will be managed by National Heart, Lung, and Blood Institute (NHLBI).

Locations

US (53)