CAPRI: Effects of COVID-19 Convalescent Plasma (CCP) on Coronavirus-associated Complications in Hospitalized Patients

• Sponsor: Priscilla Hsue, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT04421404
• Collaborator: Blood Systems Research Institute (Other), San Francisco General Hospital (Other)
• Enrollment: 34
• Locations: 3
• Arms: 2
• Actual Duration (Months): 10.7
• Patients Per Site: 11.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset of initial symptoms.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; Sars-CoV2	Biological: COVID-19 Convalescent Plasma (CCP); Biological: Placebo	Phase 2

Detailed Description

A total of 50 eligible subjects will be randomized in a 1:1 ratio to receive either convalescent fresh frozen plasma (frozen within 8 hours of collection) of PF24 (frozen within 24 hours) from blood donors who have recovered from COVID-19 containing antibodies to SARS-CoV-2 or control (standard fresh frozen plasma collected prior to 12/1/2019 or with documented negative SARS-CoV-2 antibody). Should additional anti-COVID agents (anti-viral and/or anti-inflammatory) become available for use as standard of care during implementation, the sample size will be recalculated and increased to account for the estimated impact that these agents may have on the reducing the progression to the primary endpoint of severe hypoxemia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects enrolled in the study will be randomized using a web based randomization procedure to receive convalescent plasma versus non-immune plasma at a 1:1 ratio.Subjects enrolled in the study will be randomized using a web based randomization procedure to receive convalescent plasma versus non-immune plasma at a 1:1 ratio.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Study investigators analyzing the data and participants will be blinded to the randomization. It may not be feasible to blind nursing staff to the treatment assignment to ensure proper ABO checking of the plasma unit at bedside per standard transfusion procedures, but every effort will be made to preserve blinding of the investigators, participant, and primary team providing care. An unblinded research assistant who is not involved in other aspects of the study will randomize the participant once enrolled. Randomization will be provided to an unblinded provider who is not part of the care team who will place the order for the plasma (CCP vs. control plasma) using a paper order that will not be part of the electronic medical record. The safety monitoring committee (SMC) will review study data, including unblinded data, to evaluate the safety, efficacy, study progress, and conduct of the study.
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma (CCP) to Non-immune Plasma to Limit Coronavirus-associated Complications in Hospitalized Patients
• Actual Study Start Date: Jun 9, 2020
• Actual Primary Completion Date: Apr 30, 2021
• Actual Study Completion Date: Apr 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COVID-19 Convalescent Plasma Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.	Biological: COVID-19 Convalescent Plasma (CCP); COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.
Placebo Comparator: Placebo Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.	Biological: Placebo; Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.

Outcome Measures

Primary Outcome Measures

1. Mechanical Ventilation or Death Endpoint [Day 14]

   Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.

Secondary Outcome Measures

1. Mechanical Ventilation or Death Endpoint [Day 28]

   Progression to mechanical ventilation or death within the first 28 days of enrollment.

2. 8-Point Ordinal Scale Endpoint [Day 29]

   Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for Enrollment:

1. Patients ≥18 years of age

2. Hospitalized with COVID-19

3. Enrolled within 72 hours of hospitalization OR within day 14 from first signs of illness

4. Pulmonary infiltrates on chest imaging

5. Oxygenation of <95% on room air

6. Laboratory confirmed COVID-19

Exclusion Criteria

1. Contraindication to transfusion due to inability to tolerate additional fluid, such as due to decompensated congestive heart failure

2. Baseline requirement for oxygen supplementation prior to COVID-19 infection or use of positive pressure therapy for sleep disordered breathing

3. Currently experiencing severe hypoxemic failure, as defined in study endpoints

4. Prior receipt of plasma products, IVIG, or hyperimmune globulin within past 3 months

5. Not currently enrolled another interventional clinical trial of COVID-19 treatment.

Note: If taking medications with potential anti-COVID activity for the purpose of COVID-19 treatment that do not yet have data to support efficacy, such as IL-6 antagonists, these medications must be stopped prior to enrollment. Receipt of current standard of care COVID-19 treatment, including remdesivir and dexamethasone is permitted and should be recorded as a concomitant medication.

Note: Pregnancy is not exclusionary but will merit additional discussion of risks & benefits in the context of ongoing pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco General Hospital	San Francisco	California	United States	94110
2	UCSF Medical Center at Mount Zion	San Francisco	California	United States	94115
3	University of California, San Francisco Medical Center (Parnassus Campus)	San Francisco	California	United States	94143

Sponsors and Collaborators

• Priscilla Hsue, MD
• Blood Systems Research Institute
• San Francisco General Hospital

Investigators

• Principal Investigator: Priscilla Hsue, MD, University of California, San Francisco
• Principal Investigator: Annie Leutkemeyer, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 26, 2020
• Informed Consent Form - Jul 29, 2020

More Information

Publications

None provided.

• Responsible Party: Priscilla Hsue, MD, Professor of Medicine, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT04421404
• Other Study ID Numbers: 20-30794
• First Posted: Jun 9, 2020
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Priscilla Hsue, MD, Professor of Medicine, University of California, San Francisco: COVID-19; Sars-CoV2; Convalescent plasma
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Arm/Group Title	COVID-19 Convalescent Plasma	Placebo
Arm/Group Description	Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.	Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.
Period Title: Overall Study
STARTED	16	18
COMPLETED	16	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	COVID-19 Convalescent Plasma	Placebo	Total
Arm/Group Description	Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.	Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.	Total of all reporting groups
Overall Participants	16	18	34
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	52	62	57
Sex: Female, Male (Count of Participants)
Female	10 62.5%	9 50%	19 55.9%
Male	6 37.5%	9 50%	15 44.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 75%	11 61.1%	23 67.6%
Not Hispanic or Latino	4 25%	6 33.3%	10 29.4%
Unknown or Not Reported	0 0%	1 5.6%	1 2.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 5.6%	1 2.9%
Asian	2 12.5%	2 11.1%	4 11.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.3%	1 5.6%	2 5.9%
White	3 18.8%	5 27.8%	8 23.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	10 62.5%	9 50%	19 55.9%
Region of Enrollment (Count of Participants)
United States	16 100%	18 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Mechanical Ventilation or Death Endpoint
Description	Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COVID-19 Convalescent Plasma	Placebo
Arm/Group Description	Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.	Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.
Measure Participants	16	18
Count of Participants [Participants]	2 12.5%	0 0%

2. Secondary Outcome

Title	Mechanical Ventilation or Death Endpoint
Description	Progression to mechanical ventilation or death within the first 28 days of enrollment.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COVID-19 Convalescent Plasma	Placebo
Arm/Group Description	Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.	Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.
Measure Participants	16	18
Count of Participants [Participants]	2 12.5%	0 0%

3. Secondary Outcome

Title	8-Point Ordinal Scale Endpoint
Description	Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	90 days
Arm/Group Title	COVID-19 Convalescent Plasma		Placebo
Arm/Group Description	Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.		Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.
All Cause Mortality
	COVID-19 Convalescent Plasma		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		1/18 (5.6%)
Serious Adverse Events
	COVID-19 Convalescent Plasma		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)		1/18 (5.6%)
General disorders
Death	1/16 (6.3%)		1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Intubation	2/16 (12.5%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	COVID-19 Convalescent Plasma		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)		1/18 (5.6%)
Cardiac disorders
Hypotension (transfusion reaction)	0/16 (0%)		1/18 (5.6%)
Endocrine disorders
Elevated triglycerides	1/16 (6.3%)		0/18 (0%)
Hepatobiliary disorders
Elevated LFTs	1/16 (6.3%)		0/18 (0%)
Infections and infestations
UTI	1/16 (6.3%)		0/18 (0%)

Limitations/Caveats

This study was limited by the small sample of hospitalized, hypoxic patients, limiting the generalizability of the results. Most participants were beyond 72 hours of symptom onset, the period when studies suggest CCP is most likely to be beneficial.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.