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Convalescent Plasma in Outpatients With COVID-19 (C3PO)

Primary Purpose

Covid19

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Convalescent Plasma
Saline
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Chandler Regional Medical Center
  • Valleywise Health Medical Center
  • UCSD Health La Jolla
  • Loma Linda University Medical Center
  • Ronald Reagan UCLA Medical Center
  • Cedars-Sinai Medical Center
  • UC Davis Medical Center
  • Stanford University
  • Harbor-UCLA Medical Center
  • University of Colorado Hospital
  • UF Health Shands Hospital
  • Jackson Memorial Hospital
  • Grady Memorial Hospital
  • Rush University Medical Center
  • University of Illinois Hospital
  • University of Chicago Medical Center
  • University of Iowa Hospitals & Clinics
  • University of Louisville Hospital
  • Maine Medical Center
  • Tufts Medical Center
  • Beth Israel Deaconess Medical Center
  • Newton-Wellesley Hospital
  • Baystate Medical Center
  • University of Michigan University Hospital
  • Detroit Receiving Hospital
  • Harper University Hospital
  • Henry Ford Hospital
  • Sinai-Grace Hospital
  • Spectrum Health Hospitals Butterworth Hospital
  • William Beaumont Hospital
  • William Beaumont Hospital-Troy
  • HealthPartners Methodist Hospital
  • Regions Hospital
  • Barnes Jewish Hospital
  • Cooper University Hospital
  • Robert Wood Johnson University Hospital
  • University of New Mexico Hospital
  • SUNY Downstate Medical Center
  • Duke University Hospital
  • Wake Forest Baptist Medical Center
  • University of Cincinnati Medical Center
  • OSU Wexner Medical Center
  • Mercy St. Vincent Medical Center
  • Oregon Health & Science University Hospital
  • Geisinger Medical Center
  • Temple University Hospital
  • Einstein Medical Center
  • UPMC Presbyterian Hospital
  • William P. Clements Jr. University Hospital
  • Ben Taub General Hospital
  • Memorial Hermann Texas Medical Center
  • University of Utah Healthcare
  • Froedtert Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Convalescent Plasma

Placebo

Arm Description

Participants receive 1 unit of convalescent plasma.

Participants receive 1 unit of saline with multivitamin.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization
This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity. 1 = Not hospitalized without limitation in activity (no symptoms) 2 = Not hospitalized with limitation in activity (continued symptoms) 3 = Hospitalized not on supplemental oxygen 4 = Hospitalized on supplemental oxygen by mask or nasal prongs 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula 6 = Hospitalized, intubated and mechanically ventilated 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy) 8 = Death
Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression
Assessed on the COVID Outpatient Ordinal Outcome Scale censored at 15 days after randomization. Scale provides more granular detail for outpatients than the WHO scale (adapted from Harrell and Lindsell, 2020). Worsening of symptoms is defined as any subject admitted to the hospital (level 1), seen in the emergency room (level 2), a patient who reports increased symptoms of 2 levels on the scale over a 24 hour period, or a patient who reports increased symptoms of 1 level observed for a 48 hour period. COVID Outpatient Ordinal Outcomes Scale 1 = patient requires care in the hospital 2 = patient requires care in the emergency department or urgent care 3 = patient at home with symptoms rated as moderate (defined as fever, shortness of breath, abdominal pain) 4 = patient at home with symptoms rated as mild (defined as afebrile, constitutional symptoms (flu-like illness) without shortness 5 = patient in their usual state of health
Number of Hospital-free Days During the 30 Days Following Randomization
All-cause Mortality

Full Information

First Posted
April 17, 2020
Last Updated
October 15, 2021
Sponsor
Stanford University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network, University of Pittsburgh, Medical University of South Carolina
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1. Study Identification

Unique Protocol Identification Number
NCT04355767
Brief Title
Convalescent Plasma in Outpatients With COVID-19
Acronym
C3PO
Official Title
Clinical-trial of COVID-19 Convalescent Plasma in Outpatients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
August 11, 2020 (Actual)
Primary Completion Date
March 29, 2021 (Actual)
Study Completion Date
March 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network, University of Pittsburgh, Medical University of South Carolina

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
511 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Convalescent Plasma
Arm Type
Experimental
Arm Description
Participants receive 1 unit of convalescent plasma.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants receive 1 unit of saline with multivitamin.
Intervention Type
Biological
Intervention Name(s)
Convalescent Plasma
Intervention Description
SARS-CoV-2 convalescent plasma with neutralizing SARS-CoV2 antibodies titers of ≥1:160 administered via intravenous (IV) infusion.
Intervention Type
Biological
Intervention Name(s)
Saline
Intervention Description
Saline with multivitamin administered via intravenous (IV) infusion..
Primary Outcome Measure Information:
Title
Number of Patients With Disease Progression (Intention-to-treat Population)
Description
Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.
Time Frame
15 days
Title
Number of Patients With Disease Progression (Per-protocol Population)
Description
Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization
Description
This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity. 1 = Not hospitalized without limitation in activity (no symptoms) 2 = Not hospitalized with limitation in activity (continued symptoms) 3 = Hospitalized not on supplemental oxygen 4 = Hospitalized on supplemental oxygen by mask or nasal prongs 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula 6 = Hospitalized, intubated and mechanically ventilated 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy) 8 = Death
Time Frame
30 days
Title
Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression
Description
Assessed on the COVID Outpatient Ordinal Outcome Scale censored at 15 days after randomization. Scale provides more granular detail for outpatients than the WHO scale (adapted from Harrell and Lindsell, 2020). Worsening of symptoms is defined as any subject admitted to the hospital (level 1), seen in the emergency room (level 2), a patient who reports increased symptoms of 2 levels on the scale over a 24 hour period, or a patient who reports increased symptoms of 1 level observed for a 48 hour period. COVID Outpatient Ordinal Outcomes Scale 1 = patient requires care in the hospital 2 = patient requires care in the emergency department or urgent care 3 = patient at home with symptoms rated as moderate (defined as fever, shortness of breath, abdominal pain) 4 = patient at home with symptoms rated as mild (defined as afebrile, constitutional symptoms (flu-like illness) without shortness 5 = patient in their usual state of health
Time Frame
15 days
Title
Number of Hospital-free Days During the 30 Days Following Randomization
Time Frame
30 days
Title
All-cause Mortality
Time Frame
Assessed at 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clifton W Callaway, MD, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Valerie Durkalski-Mauldin, PhD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frederick Korley, MD, PhD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sharon Yeatts, PhD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert Silbergleit, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William Barsan, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kevin Schulman, MD
Organizational Affiliation
Stanford University
Official's Role
Study Director
Facility Information:
Facility Name
Chandler Regional Medical Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Valleywise Health Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85008
Country
United States
Facility Name
UCSD Health La Jolla
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
UF Health Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
Jackson Memorial Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Illinois Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Iowa Hospitals & Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Louisville Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Newton-Wellesley Hospital
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02462
Country
United States
Facility Name
Baystate Medical Center
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
University of Michigan University Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Detroit Receiving Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Harper University Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Sinai-Grace Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48235
Country
United States
Facility Name
Spectrum Health Hospitals Butterworth Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
William Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
William Beaumont Hospital-Troy
City
Troy
State/Province
Michigan
ZIP/Postal Code
48085
Country
United States
Facility Name
HealthPartners Methodist Hospital
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55426
Country
United States
Facility Name
Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Barnes Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cooper University Hospital
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Robert Wood Johnson University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
University of New Mexico Hospital
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
SUNY Downstate Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Duke University Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
OSU Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Mercy St. Vincent Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
Oregon Health & Science University Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Einstein Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
UPMC Presbyterian Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
William P. Clements Jr. University Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Ben Taub General Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Memorial Hermann Texas Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Healthcare
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The complete de-identified patient data set will be shared.
IPD Sharing Time Frame
Data will be available indefinitely.
IPD Sharing Access Criteria
Data requests will be managed by National Heart, Lung, and Blood Institute (NHLBI).
IPD Sharing URL
https://biodatacatalyst.nhlbi.nih.gov/
Citations:
PubMed Identifier
34407339
Citation
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.
Results Reference
result
Links:
URL
https://siren.network/
Description
SIREN Network
URL
http://hbiostat.org/proj/covid19/bayesplan.html
Description
Statistical Design and Analysis Plan for Sequential Parallel-Group RCT for COVID-19 (Harrell and Lindsell, 2020)
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://biodatacatalyst.nhlbi.nih.gov/

Learn more about this trial

Convalescent Plasma in Outpatients With COVID-19

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