Covid19Phase 3C3PONCT04355767

Convalescent Plasma in Outpatients With COVID-19

A Phase 3 study testing Convalescent Plasma and Saline in people with Covid19, run by Stanford University at 53 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Covid19
What is being tested?: Convalescent Plasma and Saline
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 511 participants
Where: 53 sitesUnited States
Study dates: 11 Aug 2020to 29 Mar 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

53 sites in 1 country.

City, postcode or hospital

53 sites in 1 country

United States53 sites

University of New Mexico Hospital
Albuquerque, New Mexico, 87106
University of Michigan University Hospital
Ann Arbor, Michigan, 48109
Grady Memorial Hospital
Atlanta, Georgia, 30303
University of Colorado Hospital
Aurora, Colorado, 80045
Tufts Medical Center
Boston, Massachusetts, 02111
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
SUNY Downstate Medical Center
Brooklyn, New York, 11203
Cooper University Hospital
Camden, New Jersey, 08103
Chandler Regional Medical Center
Chandler, Arizona, 85224
Rush University Medical Center
Chicago, Illinois, 60612
University of Illinois Hospital
Chicago, Illinois, 60612
University of Chicago Medical Center
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
OSU Wexner Medical Center
Columbus, Ohio, 43210
William P. Clements Jr. University Hospital
Dallas, Texas, 75235
Geisinger Medical Center
Danville, Pennsylvania, 17822
Detroit Receiving Hospital
Detroit, Michigan, 48201
Harper University Hospital
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Sinai-Grace Hospital
Detroit, Michigan, 48235
Duke University Hospital
Durham, North Carolina, 27710
UF Health Shands Hospital
Gainesville, Florida, 32608
Spectrum Health Hospitals Butterworth Hospital
Grand Rapids, Michigan, 49503
Ben Taub General Hospital
Houston, Texas, 77030
Memorial Hermann Texas Medical Center
Houston, Texas, 77030
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
UCSD Health La Jolla
La Jolla, California, 92037
Loma Linda University Medical Center
Loma Linda, California, 92354
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Cedars-Sinai Medical Center
Los Angeles, California, 90211
University of Louisville Hospital
Louisville, Kentucky, 40202
Jackson Memorial Hospital
Miami, Florida, 33136
Froedtert Hospital
Milwaukee, Wisconsin, 53226
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08901
Newton-Wellesley Hospital
Newton, Massachusetts, 02462
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Valleywise Health Medical Center
Phoenix, Arizona, 85008
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
Maine Medical Center
Portland, Maine, 04102
Oregon Health & Science University Hospital
Portland, Oregon, 97239
William Beaumont Hospital
Royal Oak, Michigan, 48073
UC Davis Medical Center
Sacramento, California, 95817
HealthPartners Methodist Hospital
Saint Louis Park, Minnesota, 55426
Regions Hospital
Saint Paul, Minnesota, 55101
University of Utah Healthcare
Salt Lake City, Utah, 84132
Baystate Medical Center
Springfield, Massachusetts, 01199
Barnes Jewish Hospital
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
Mercy St. Vincent Medical Center
Toledo, Ohio, 43608
Harbor-UCLA Medical Center
Torrance, California, 90502
William Beaumont Hospital-Troy
Troy, Michigan, 48085
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: Clinical-trial of COVID-19 Convalescent Plasma in Outpatients

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
Being tested: Convalescent Plasma, Saline
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04355767
Study group	Role	What they receive
Convalescent Plasma	Experimental	Participants receive 1 unit of convalescent plasma. Receives: Biological: Convalescent Plasma
Placebo	Placebo comparator	Participants receive 1 unit of saline with multivitamin. Receives: Biological: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 15 days

Secondary outcomes (4)

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
Measured: 30 days
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
Measured: 15 days
Number of Hospital-free Days During the 30 Days Following Randomization
Measured: 30 days
All-cause Mortality
Measured: Assessed at 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Aug 202029 Mar 2021

First posted21 Apr 2020
Study start11 Aug 2020
Primary completion29 Mar 2021
Study completion29 Mar 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Covid19Studies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 511 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04355767
Sponsor's protocol ID: C3PO
Other IDs: 1OT2HL156812-01
Acronym: C3PO
Status last verified: Oct 2021
First submitted: 17 Apr 2020
Last updated: 19 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: The complete de-identified patient data set will be shared.

Publications

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.
PubMed 34407339

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical-trial of COVID-19 Convalescent Plasma in Outpatients
ClinicalTrials.gov ID: NCT04355767
Acronym / sponsor ID: C3PO / C3PO
Conditions: Covid19
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 511 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Strategies to Innovate EmeRgENcy Care Clinical Trials Network, University of Pittsburgh, Medical University of South Carolina
Study start: 11 Aug 2020 (actual)
Primary completion: 29 Mar 2021 (actual)
Study completion: 29 Mar 2021 (actual)
First posted: 21 Apr 2020 (actual)
Results: Posted 19 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Convalescent Plasma	Experimental	Biological: Convalescent PlasmaParticipants receive 1 unit of convalescent plasma.
Placebo	Placebo comparator	Biological: SalineParticipants receive 1 unit of saline with multivitamin.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Convalescent PlasmaSARS-CoV-2 convalescent plasma with neutralizing SARS-CoV2 antibodies titers of ≥1:160 administered via intravenous (IV) infusion.	Biological	Convalescent Plasma
SalineSaline with multivitamin administered via intravenous (IV) infusion..	Biological	Placebo

Primary outcome

Number of Patients With Disease Progression (Intention-to-treat Population)
Time frame: 15 days
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)
Time frame: 15 days
Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

4 secondary outcomes

Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization
Time frame: 30 days
Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression
Time frame: 15 days
Number of Hospital-free Days During the 30 Days Following Randomization
Time frame: 30 days
All-cause Mortality
Time frame: Assessed at 30 days

Results and safety

Results posted to the registry on 19 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Convalescent Plasma	257	250
Placebo	254	251

Primary outcome: Number of Patients With Disease Progression (Intention-to-treat Population)

Time frame: 15 days. Count of participants. Unit: Participants

Measure	Convalescent Plasma n = 257	Placebo n = 254
Patients with a disease-progression event	77	81
Hospital admission for any reason	51	56
Seeking emergency or urgent care	25	25
Death without hospitalization	1	0

Convalescent Plasma vs Placebo: Risk Difference (RD): 2.2 (95% CI -5.9 to 10.4)

Population analysed: Intention-to-treat population included all randomized participants.

Primary outcome: Number of Patients With Disease Progression (Per-protocol Population)

Time frame: 15 days. Count of participants. Unit: Participants

Measure	Convalescent Plasma n = 246	Placebo n = 251
Patients with a disease-progression event	71	80
Hospital admission for any reason	47	55
Seeking emergency or urgent care	24	25
Death without hospitalization	0	0

Population analysed: Per-protocol population included all the patients who had undergone randomization after the exclusion of those who did not receive the assigned trial product, had an identified eligibility violation, or had a disease-progression event before the initiation of treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 30 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Convalescent Plasma	59 of 257 (23%)	51 of 257 (19.8%)	5 of 257
Placebo	64 of 254 (25.2%)	35 of 254 (13.8%)	1 of 254

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 34407339Korley 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.
Statistical Design and Analysis Plan for Sequential Parallel-Group RCT for COVID-19 (Harrell and Lindsell, 2020)Link provided by the sponsor.
Individual participant dataSharing planned: Yes. The complete de-identified patient data set will be shared.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clifton W Callaway, MD, PhD principal investigator

University of Pittsburgh

Valerie Durkalski-Mauldin, PhD principal investigator

Medical University of South Carolina

Frederick Korley, MD, PhD principal investigator

University of Michigan

53 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Convalescent Plasma and Saline in people with Covid19, run by Stanford University at 53 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Disease Progression (Intention-to-treat Population) (time frame: 15 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04355767, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2021.