Back to resultsCOVID-19 Convalescent Plasma for the Treatment of Hospitalized Patients With Pneumonia Caused by SARS-CoV-2.
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
COVID-19 Convalescent Plasma
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Convalescent plasma
Eligibility Criteria
Inclusion Criteria:
- Adult ≥18 years of age
Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other authorized or approved assay in any specimen collected within 72 hours prior to enrollment.
Note - An exception must be requested to the Sponsor if ≥72 hours since positive test.
- Hospitalized in participating facility.
- Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan).
Abnormal respiratory status that is judged worse than baseline by the investigator and as documented at any point within 24 hours prior to randomization, consistent with ordinal scale levels 5, 6 or 7, specifically defined as:
- Room air saturation of oxygen (SaO2) < 93%, OR
- Requiring supplemental oxygen, OR
- Tachypnea with respiratory rate ≥30
- Patient or proxy is willing and able to provide written informed consent and comply with all protocol requirements
Exclusion Criteria:
- Contraindication to transfusion (e.g., severe volume overload, history of severe allergic reaction to blood products), as judged by the investigator.
- Clinical suspicion that the etiology of acute illness (acute decompensation) is primarily due to a condition other than COVID-19
- Receipt of other investigational therapy as a part of another clinical trial. Note: investigational therapies used as part of clinical care, (eg, remdesivir, hydroxychloroquine) are permissible.
Sites / Locations
- Hospital of the University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
COVID-19 Convalescent plasma
Standard care
Arm Description
COVID-19 Convalescent plasma on Study Day 1 in addition to standard care
Standard care alone
Outcomes
Primary Outcome Measures
Participants With Serious Adverse Events.
Number of participants with at least one serious adverse events (SAEs) up to Study Day 29.
Clinical Severity Score
Clinical Severity Score (CSC) measured by both survival time, time to recovery (defined by reaching levels 1-3 of the WHO modified 8-Point Ordinal Severity scale), and disease course while hospitalized and is calculated based on a procedure proposed by Shaw and Fay 2016 (https://doi.org/10.1002/sim.6950). CSC ranges from 1 to 57. Higher CSC is worse outcome.
Clinical status assessment (WHO modified 8-Point Ordinal Severity scale) includes:
Not hospitalized, no limitations on activities.
Not hospitalized, limitation on activities and/or requiring home oxygen;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death
Secondary Outcome Measures
Clinical Status Assessment, Time to Recovery
Time to recovery, defined by time needed to reach levels 1-3 using the WHO modified 8-Point Ordinal Severity scale assessed daily while hospitalized and on Day 15, 22, and 29:
Not hospitalized, no limitations on activities.
Not hospitalized, limitation on activities and/or requiring home oxygen;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death
National Early Warning Score (NEWS) Clinical Status Assessment
Time to discharge or to a National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours, whichever occurs first. NEWS assessed daily while hospitalized until discharge or death and on Days 15 and 29.
Higher NEWS is worse, range from 0 to 20.
Oxygenation
Days of supplemental oxygen while in hospital. defined as days with WHO8 ordinal score of 5, 6, or 7
Incidence of New Oxygenation Use up to Day 29
Incidence of new oxygenation use up to Day 29.
Duration of New Oxygen Use up to Day 29
Duration (days) of new oxygen use up to Day 29.
Non-invasive Ventilation/High Flow Oxygen Days up to Day 29
Days of non-invasive ventilation/high flow oxygen up to Day 29 Defined by having a WHO8 ordinal scale of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices
Number of Participants With at Least One Day on Non-invasive Ventilation/High Flow Oxygen up to Day 29
number of participants with at least one day on non-invasive ventilation/high flow oxygen Defined by having a WHO8 ordinal scale of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices
Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29
Days of non-invasive ventilation/high flow oxygen up to Day 29
Ventilator/ECMO Days to Day 29
Days of mechanical ventilation or ECMO use (having a WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO) during the study in hospital until study day 29.
New Mechanical Ventilation or ECMO Use
number of subjects with new mechanical ventilation or ECMO use up to Day 29 since all subjects were not on mechanical ventilation or ECMO at baseline.
Duration of New Mechanical Ventilation or ECMO
Days of new mechanical ventilation or ECMO use up to Day 29.
Duration of Hospitalization
Duration (days) of first hospitalization. Time until death or discharge or Study Day 29
Mortality
28 day mortality.
Number of Subjects With SAEs Through Day 29
Number of subjects with SAEs through Day 29.
Number of Subjects With at Least One Grade 3 and Grade 4 Clinical and/or Laboratory Adverse Events Through Day 29
Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events (AEs) through Day 29.
Changes in WBC With Differential Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in Hemoglobin Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in Platelets Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in Creatinine Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in Glucose Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in Total Bilirubin Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in ALT Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in AST Measurement Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Changes in PT Measurement Laboratory Through Day 29
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Full Information
NCT ID
NCT04397757
First Posted
May 19, 2020
Last Updated
March 31, 2022
Sponsor
University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT04397757
Brief Title
COVID-19 Convalescent Plasma for the Treatment of Hospitalized Patients With Pneumonia Caused by SARS-CoV-2.
Official Title
An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants With COVID-19 Pneumonia Caused by SARS-CoV-2.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
May 13, 2020 (Actual)
Primary Completion Date
February 6, 2021 (Actual)
Study Completion Date
March 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
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 purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.
Detailed Description
This open-label, randomized, controlled, phase 1 trial will assess the safety and efficacy of convalescent plasma in severely ill, hospitalized participants with pneumonia due to COVID-19. This study will enroll adults 18 years old and older, including pregnant women.
A total of 80 eligible participants will be randomized to receive either 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19 and standard of care (treatment arm) or standard of care alone (control arm). Participants in the treatment arm will receive 2 units of convalescent plasma on Study Day 1 in addition to standard of care.
Participants will be assessed on study Day 1 (pre-dose), 30 minutes after each unit of plasma, on all Study Days while hospitalized, and Study Days 15, 22, 29, and 60. All participants will undergo a series of safety and efficacy, assessments. Blood samples will be collected on Days 1 (prior to plasma administration), 3, 8, 15, 29, and 60. Oropharyngeal or endotracheal samples will be collected on Days 1 (prior to plasma administration), 3, 5, 8, 11, and 15.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Convalescent plasma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized 1:1 to receive either convalescent plasma on Study Day 1 in addition to standard care or standard care alone.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
COVID-19 Convalescent plasma
Arm Type
Experimental
Arm Description
COVID-19 Convalescent plasma on Study Day 1 in addition to standard care
Arm Title
Standard care
Arm Type
No Intervention
Arm Description
Standard care alone
Intervention Type
Biological
Intervention Name(s)
COVID-19 Convalescent Plasma
Intervention Description
2 units of COVID-19 convalescent plasma compatible with their blood type
Primary Outcome Measure Information:
Title
Participants With Serious Adverse Events.
Description
Number of participants with at least one serious adverse events (SAEs) up to Study Day 29.
Time Frame
Up to Study Day 29
Title
Clinical Severity Score
Description
Clinical Severity Score (CSC) measured by both survival time, time to recovery (defined by reaching levels 1-3 of the WHO modified 8-Point Ordinal Severity scale), and disease course while hospitalized and is calculated based on a procedure proposed by Shaw and Fay 2016 (https://doi.org/10.1002/sim.6950). CSC ranges from 1 to 57. Higher CSC is worse outcome.
Clinical status assessment (WHO modified 8-Point Ordinal Severity scale) includes:
Not hospitalized, no limitations on activities.
Not hospitalized, limitation on activities and/or requiring home oxygen;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death
Time Frame
Up to Study Day 29
Secondary Outcome Measure Information:
Title
Clinical Status Assessment, Time to Recovery
Description
Time to recovery, defined by time needed to reach levels 1-3 using the WHO modified 8-Point Ordinal Severity scale assessed daily while hospitalized and on Day 15, 22, and 29:
Not hospitalized, no limitations on activities.
Not hospitalized, limitation on activities and/or requiring home oxygen;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death
Time Frame
Up to Study Day 29
Title
National Early Warning Score (NEWS) Clinical Status Assessment
Description
Time to discharge or to a National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours, whichever occurs first. NEWS assessed daily while hospitalized until discharge or death and on Days 15 and 29.
Higher NEWS is worse, range from 0 to 20.
Time Frame
Up to Study Day 29
Title
Oxygenation
Description
Days of supplemental oxygen while in hospital. defined as days with WHO8 ordinal score of 5, 6, or 7
Time Frame
Daily while hospitalized and up to Study Day 29
Title
Incidence of New Oxygenation Use up to Day 29
Description
Incidence of new oxygenation use up to Day 29.
Time Frame
From enrollment to Day 29.
Title
Duration of New Oxygen Use up to Day 29
Description
Duration (days) of new oxygen use up to Day 29.
Time Frame
From enrollment to Day 29.
Title
Non-invasive Ventilation/High Flow Oxygen Days up to Day 29
Description
Days of non-invasive ventilation/high flow oxygen up to Day 29 Defined by having a WHO8 ordinal scale of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices
Time Frame
Daily while in hospital to Study Day 29.
Title
Number of Participants With at Least One Day on Non-invasive Ventilation/High Flow Oxygen up to Day 29
Description
number of participants with at least one day on non-invasive ventilation/high flow oxygen Defined by having a WHO8 ordinal scale of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices
Time Frame
Daily while in hospital until Study Day 29
Title
Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29
Description
Days of non-invasive ventilation/high flow oxygen up to Day 29
Time Frame
Daily while in hospital to Study Day 29.
Title
Ventilator/ECMO Days to Day 29
Description
Days of mechanical ventilation or ECMO use (having a WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO) during the study in hospital until study day 29.
Time Frame
Daily while in hospital to Study Day 29
Title
New Mechanical Ventilation or ECMO Use
Description
number of subjects with new mechanical ventilation or ECMO use up to Day 29 since all subjects were not on mechanical ventilation or ECMO at baseline.
Time Frame
From enrollment to Day 29.
Title
Duration of New Mechanical Ventilation or ECMO
Description
Days of new mechanical ventilation or ECMO use up to Day 29.
Time Frame
Daily while in hospital to Study Day 29
Title
Duration of Hospitalization
Description
Duration (days) of first hospitalization. Time until death or discharge or Study Day 29
Time Frame
To Study Day 29
Title
Mortality
Description
28 day mortality.
Time Frame
28 days from Study Day 1
Title
Number of Subjects With SAEs Through Day 29
Description
Number of subjects with SAEs through Day 29.
Time Frame
Through Study Day 29
Title
Number of Subjects With at Least One Grade 3 and Grade 4 Clinical and/or Laboratory Adverse Events Through Day 29
Description
Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events (AEs) through Day 29.
Time Frame
Through Study Day 29
Title
Changes in WBC With Differential Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29
Title
Changes in Hemoglobin Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29
Title
Changes in Platelets Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29.
Title
Changes in Creatinine Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29.
Title
Changes in Glucose Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29.
Title
Changes in Total Bilirubin Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29
Title
Changes in ALT Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29
Title
Changes in AST Measurement Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29.
Title
Changes in PT Measurement Laboratory Through Day 29
Description
Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value.
Time Frame
Through Day 29.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult ≥18 years of age
Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other authorized or approved assay in any specimen collected within 72 hours prior to enrollment.
Note - An exception must be requested to the Sponsor if ≥72 hours since positive test.
Hospitalized in participating facility.
Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan).
Abnormal respiratory status that is judged worse than baseline by the investigator and as documented at any point within 24 hours prior to randomization, consistent with ordinal scale levels 5, 6 or 7, specifically defined as:
Room air saturation of oxygen (SaO2) < 93%, OR
Requiring supplemental oxygen, OR
Tachypnea with respiratory rate ≥30
Patient or proxy is willing and able to provide written informed consent and comply with all protocol requirements
Exclusion Criteria:
Contraindication to transfusion (e.g., severe volume overload, history of severe allergic reaction to blood products), as judged by the investigator.
Clinical suspicion that the etiology of acute illness (acute decompensation) is primarily due to a condition other than COVID-19
Receipt of other investigational therapy as a part of another clinical trial. Note: investigational therapies used as part of clinical care, (eg, remdesivir, hydroxychloroquine) are permissible.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katharine J. Bar
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36351430
Citation
Herman JD, Wang C, Burke JS, Zur Y, Compere H, Kang J, Macvicar R, Taylor S, Shin S, Frank I, Siegel D, Tebas P, Choi GH, Shaw PA, Yoon H, Pirofski LA, Julg BD, Bar KJ, Lauffenburger D, Alter G. Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy. Cell Rep Med. 2022 Nov 15;3(11):100811. doi: 10.1016/j.xcrm.2022.100811. Epub 2022 Oct 24.
Results Reference
derived
PubMed Identifier
34788233
Citation
Bar KJ, Shaw PA, Choi GH, Aqui N, Fesnak A, Yang JB, Soto-Calderon H, Grajales L, Starr J, Andronov M, Mastellone M, Amonu C, Feret G, DeMarshall M, Buchanan M, Caturla M, Gordon J, Wanicur A, Monroy MA, Mampe F, Lindemuth E, Gouma S, Mullin AM, Barilla H, Pronina A, Irwin L, Thomas R, Eichinger RA, Demuth F, Luning Prak ET, Pascual JL, Short WR, Elovitz MA, Baron J, Meyer NJ, Degnan KO, Frank I, Hensley SE, Siegel DL, Tebas P. A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia. J Clin Invest. 2021 Dec 15;131(24):e155114. doi: 10.1172/JCI155114.
Results Reference
derived
Learn more about this trial
COVID-19 Convalescent Plasma for the Treatment of Hospitalized Patients With Pneumonia Caused by SARS-CoV-2.
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