Convalescent Plasma in Outpatients With COVID-19 (C3PO)

• ClinicalTrials.gov Identifier: NCT04355767
• Recruitment Status: Not yet recruiting
• First Posted: April 21, 2020
• Last Update Posted: June 26, 2020
• Sponsor: Stanford University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network
• Information provided by (Responsible Party): Stanford University

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 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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: Convalescent Plasma; Biological: Saline	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical-trial of COVID-19 Convalescent Plasma in Outpatients
• Estimated Study Start Date: July 2020
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Convalescent Plasma; Participants receive 1 unit of convalescent plasma.	Biological: Convalescent Plasma; SARS-CoV-2 convalescent plasma with neutralizing SARS-CoV2 antibodies titers of ≥1:160 administered via intravenous (IV) infusion.
Placebo Comparator: Placebo; Participants receive 1 unit of saline with multivitamin.	Biological: Saline; Saline with multivitamin administered via intravenous (IV) infusion..

Outcome Measures

Primary Outcome Measures :

1. Number of patients with disease progression [ Time Frame: 15 days ]
   Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

Secondary Outcome Measures :

1. Worst severity rating on the WHO COVID Ordinal Scale for Clinical Improvement during the 30 days following randomization [ Time Frame: 30 days ]

   This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity.

   • 8 = Death
   • 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy)
   • 6 = Hospitalized, intubated and mechanically ventilated
   • 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula
   • 4 = Hospitalized on supplemental oxygen by mask or nasal prongs
   • 3 = Hospitalized not on supplemental oxygen
   • 2 = Not hospitalized with limitation in activity (continued symptoms)
   • 1 = Not hospitalized without limitation in activity (no symptoms)
2. Time to disease progression [ Time Frame: 15 days ]

   Time to disease progression 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 ED 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
3. Number of Hospital-free days during the 30 days following randomization [ Time Frame: 30 days ]
4. All-cause mortality [ Time Frame: Assessed at 30 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15260

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Stanford University

National Heart, Lung, and Blood Institute (NHLBI)

Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network

Investigators

• Principal Investigator: 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

More Information

Additional Information:

SIREN Network 

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

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT04355767
• Other Study ID Numbers: C3PO
• First Posted: April 21, 2020
• Last Update Posted: June 26, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: There is no current plan to share individual participant data (IPD).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No