COVID-19 Convalescent Plasma for Mechanically Ventilated Population

• ClinicalTrials.gov Identifier: NCT04388527
• Recruitment Status: Completed
• First Posted: May 14, 2020
• Results First Posted: April 4, 2022
• Last Update Posted: April 4, 2022
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

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.

Condition or disease	Intervention/treatment	Phase
Covid-19	Biological: COVID-19 Convalescent Plasma	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 30, 2020
• Actual Primary Completion Date: January 25, 2021
• Actual Study Completion Date: January 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment; Penn COVID-19 convalescent plasma	Biological: COVID-19 Convalescent Plasma; Participants will receive 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19.

Outcome Measures

Primary Outcome Measures :

1. Participants With Serious Adverse Events. [ Time Frame: Up to Study Day 29 ]
   Cumulative incidence of participants with at least one serious adverse events (SAEs) at Study Day 29.
2. Time to Clinical Improvement. [ Time Frame: Up to Study Day 29 ]
   Time to removal from mechanical ventilation.

Secondary Outcome Measures :

1. Clinical Status Assessment, Using 8-point Ordinal Scale, of Convalescent Plasma Administration [ Time Frame: Up to Study Day 29 ]

   Time to improvement by at least 2 category from Day 1 (time to reach WHO8 <=5). WHO8 score:

   1. Not hospitalized, no limitations on activities.
   2. Not hospitalized, limitation on activities and/or requiring home oxygen;
   3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
   4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
   5. Hospitalized, requiring supplemental oxygen;
   6. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
   7. Hospitalized, on invasive mechanical ventilation or ECMO;
   8. Death
2. Clinical Status Assessment Using the National Early Warning Score (NEWS) of Convalescent Plasma Administration [ Time Frame: Up to Study Day 29 ]

   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.

3. Incidence of New Oxygenation Use up to Day 29 of Convalescent Plasma Administration [ Time Frame: From enrollment to Day 29. ]
   Incidence of new oxygenation use up to Day 29.
4. Duration of New Oxygen Use up to Day 29 of Convalescent Plasma Administration [ Time Frame: From enrollment to Day 29. ]
   Days of new oxygen use up to Day 29.
5. Oxygenation [ Time Frame: Daily while hospitalized up to Study Day 29. ]
   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.
6. Non-invasive Ventilation/High Flow Oxygen Days up to Day 29 of Convalescent Plasma Administration. [ Time Frame: Daily while in hospital to Study Day 29. ]
   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
7. Number of Subjects With at Least One Day of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration. [ Time Frame: Daily while in hospital to Study Day 29. ]
   Number of subjects with at least one day of non-invasive ventilation (WHO8 ordinal score of 6) while in hospital
8. Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration. [ Time Frame: Daily while in hospital to Study Day 29. ]
   Days of non-invasive ventilation/high flow oxygen up to Day 29.
9. Invasive Ventilation/ Extracorporeal Membrane Oxygenation(ECMO) Days [ Time Frame: Daily while in hospital to Study Day 29 ]
   Days on Invasive Ventilator/ECMO defined as WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO
10. Incidence of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration. [ Time Frame: From enrollment to Day 29. ]
    Incidence of new mechanical ventilation or ECMO use up to Day 29.
11. Duration of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration. [ Time Frame: From enrollment to Day 29. ]
    Days of new mechanical ventilation or ECMO use up to Day 29.
12. Duration of Hospitalization [ Time Frame: To Study Day 29 ]
    Duration (days) of first hospitalization. Time until death or discharge or Study Day 29
13. Mortality [ Time Frame: 28 days from Study Day 1 ]
    28 day mortality
14. Serious Adverse Events (SAEs) Through Day 29 of Convalescent Plasma Administration. [ Time Frame: Through Study Day 29. ]
    subjects with Serious Adverse Events (SAEs) through Day 29.
15. 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. [ Time Frame: Through Study Day 29 ]
    Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events through Day 29.
16. Changes in WBC With Differential Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
17. Changes in Hemoglobin Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
18. Changes in Platelets Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
19. Changes in Creatinine Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
20. Changes in Glucose Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
21. Changes in Total Bilirubin Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
22. Changes in ALT Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
23. Changes in AST Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.
24. Changes in PT Measurement Through Day 29 of Convalescent Plasma Administration. [ Time Frame: 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.

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:

1. Adult ≥18 years of age
2. 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.
3. Hospitalized, on invasive mechanical ventilation or ECMO, consistent with a clinical status assessment 8-point ordinal scale severity score of 7.
4. Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan).
5. Patient or proxy is willing and able to provide written informed consent and comply with all protocol requirements.

Exclusion Criteria:

1. Contraindication to transfusion (e.g., severe volume overload, history of severe allergic reaction to blood products), as judged by the investigator.
2. Clinical suspicion that the etiology of acute illness (acute decompensation) is primarily due to a condition other than COVID-19
3. 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.

Contacts and Locations

Locations

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

Investigators

• Principal Investigator: Katharine J. Bar, MD; University of Pennsylvania

  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:

Study Protocol and Statistical Analysis Plan  [PDF] August 28, 2020

More Information

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04388527
• Other Study ID Numbers: 842996 (PennCCP-01)
• First Posted: May 14, 2020
• Results First Posted: April 4, 2022
• Last Update Posted: April 4, 2022
• Last Verified: March 2022

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

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases