Back to resultsCOVID-19 Convalescent Plasma for Mechanically Ventilated Population
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
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, on invasive mechanical ventilation or ECMO, consistent with a clinical status assessment 8-point ordinal scale severity score of 7.
- Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan).
- 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. a. 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 Type
Experimental
Arm Label
Treatment
Arm Description
Penn COVID-19 convalescent plasma
Outcomes
Primary Outcome Measures
Participants With Serious Adverse Events.
Cumulative incidence of participants with at least one serious adverse events (SAEs) at Study Day 29.
Time to Clinical Improvement.
Time to removal from mechanical ventilation.
Secondary Outcome Measures
Clinical Status Assessment, Using 8-point Ordinal Scale, of Convalescent Plasma Administration
Time to improvement by at least 2 category from Day 1 (time to reach WHO8 <=5). WHO8 score:
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
Clinical Status Assessment Using the National Early Warning Score (NEWS) of Convalescent Plasma Administration
Time to discharge or to a 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.
Incidence of New Oxygenation Use up to Day 29 of Convalescent Plasma Administration
Incidence of new oxygenation use up to Day 29.
Duration of New Oxygen Use up to Day 29 of Convalescent Plasma Administration
Days of new oxygen use up to Day 29.
Oxygenation
Days of supplemental oxygen while in hospital up to Study Day 29. In hospital supplemental oxygen days counted as days with a WHO8 ordinal score of 5, 6, or 7.
Non-invasive Ventilation/High Flow Oxygen Days up to Day 29 of Convalescent Plasma Administration.
Days of non-invasive ventilation/high flow oxygen while in hospital up to Day 29, defined as having WHO8 ordinal score of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices
Number of Subjects With at Least One Day of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration.
Number of subjects with at least one day of non-invasive ventilation (WHO8 ordinal score of 6) while in hospital
Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration.
Days of non-invasive ventilation/high flow oxygen up to Day 29.
Invasive Ventilation/ Extracorporeal Membrane Oxygenation(ECMO) Days
Days on Invasive Ventilator/ECMO defined as WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO
Incidence of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration.
Incidence of new mechanical ventilation or ECMO use up to Day 29.
Duration of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration.
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
Serious Adverse Events (SAEs) Through Day 29 of Convalescent Plasma Administration.
subjects with Serious Adverse Events (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 of Convalescent Plasma Administration.
Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events through Day 29.
Changes in WBC With Differential Through Day 29 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 Through Day 29 of Convalescent Plasma Administration.
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
1. Study Identification
Unique Protocol Identification Number
NCT04388527
Brief Title
COVID-19 Convalescent Plasma for Mechanically Ventilated Population
Official Title
An Open-Label, Single Arm, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill Mechanically Ventilated Participants With COVID-19 Caused by SARS-CoV-2
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
April 30, 2020 (Actual)
Primary Completion Date
January 25, 2021 (Actual)
Study Completion Date
January 30, 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 can improve patients' health when they are sick with COVID-19.
Detailed Description
This open-label, single arm, phase 1 trial will assess the safety and efficacy of convalescent plasma in severely ill, mechanically ventilated participants with pneumonia due to COVID-19. This study will enroll adults 18 years old and older, including pregnant women. A total of 50 eligible participants will receive 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19. Participants will receive convalescent plasma on Study Day 1 in addition to standard of care. Participants will be assessed daily while hospitalized and then on Study Days 15, 22, 29, and 60. All participants will undergo a series of safety, efficacy, and laboratory assessments. Blood samples will be collected on Days 1 (prior to plasma administration), 3, 5, 8, 11, 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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Penn COVID-19 convalescent plasma
Intervention Type
Biological
Intervention Name(s)
COVID-19 Convalescent Plasma
Intervention Description
Participants will receive 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19.
Primary Outcome Measure Information:
Title
Participants With Serious Adverse Events.
Description
Cumulative incidence of participants with at least one serious adverse events (SAEs) at Study Day 29.
Time Frame
Up to Study Day 29
Title
Time to Clinical Improvement.
Description
Time to removal from mechanical ventilation.
Time Frame
Up to Study Day 29
Secondary Outcome Measure Information:
Title
Clinical Status Assessment, Using 8-point Ordinal Scale, of Convalescent Plasma Administration
Description
Time to improvement by at least 2 category from Day 1 (time to reach WHO8 <=5). WHO8 score:
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
Clinical Status Assessment Using the National Early Warning Score (NEWS) of Convalescent Plasma Administration
Description
Time to discharge or to a 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
Incidence of New Oxygenation Use up to Day 29 of Convalescent Plasma Administration
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 of Convalescent Plasma Administration
Description
Days of new oxygen use up to Day 29.
Time Frame
From enrollment to Day 29.
Title
Oxygenation
Description
Days of supplemental oxygen while in hospital up to Study Day 29. In hospital supplemental oxygen days counted as days with a WHO8 ordinal score of 5, 6, or 7.
Time Frame
Daily while hospitalized up to Study Day 29.
Title
Non-invasive Ventilation/High Flow Oxygen Days up to Day 29 of Convalescent Plasma Administration.
Description
Days of non-invasive ventilation/high flow oxygen while in hospital up to Day 29, defined as having WHO8 ordinal score 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 Subjects With at Least One Day of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration.
Description
Number of subjects with at least one day of non-invasive ventilation (WHO8 ordinal score of 6) while in hospital
Time Frame
Daily while in hospital to Study Day 29.
Title
Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration.
Description
Days of non-invasive ventilation/high flow oxygen up to Day 29.
Time Frame
Daily while in hospital to Study Day 29.
Title
Invasive Ventilation/ Extracorporeal Membrane Oxygenation(ECMO) Days
Description
Days on Invasive Ventilator/ECMO defined as WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO
Time Frame
Daily while in hospital to Study Day 29
Title
Incidence of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration.
Description
Incidence of new mechanical ventilation or ECMO use up to Day 29.
Time Frame
From enrollment to Day 29.
Title
Duration of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration.
Description
Days of new mechanical ventilation or ECMO use up to Day 29.
Time Frame
From enrollment to 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
Serious Adverse Events (SAEs) Through Day 29 of Convalescent Plasma Administration.
Description
subjects with Serious Adverse Events (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 of Convalescent Plasma Administration.
Description
Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events through Day 29.
Time Frame
Through Study Day 29
Title
Changes in WBC With Differential Through Day 29 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 of Convalescent Plasma Administration.
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 Through Day 29 of Convalescent Plasma Administration.
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, on invasive mechanical ventilation or ECMO, consistent with a clinical status assessment 8-point ordinal scale severity score of 7.
Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan).
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. a. 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, MD
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
Learn more about this trial
COVID-19 Convalescent Plasma for Mechanically Ventilated Population
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