Treatment of Severe Coronavirus Disease 2019 (COVID-19) With Convalescent Plasma

Study Overview
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Brief Summary
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The investigators hypothesize that use of convalescent plasma donated from individuals recovered from Coronavirus Disease 2019 (COVID-19) will help expedite recovery of individuals with active, severe COVID-19 infection.

Detailed Description
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The purpose of this research study is to see if convalescent plasma is safe and effective for the treatment of patients acutely ill with COVID-19. The researchers want to confirm the right dose levels of immunoglobulins/antibodies (immune proteins) and find out what therapeutic effects plasma donated by recovered individuals has on people severely sick with COVID-19.

Official Title
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Treatment of Severe Coronavirus Disease 2019 (COVID-19) With Convalescent Plasma Collected From Individuals With Documented Infection and Recovery From COVID-19 (SARS-CoV-2)

Conditions
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Covid-19

Intervention / Treatment
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* Biological: Convalescent plasma transfusion


Participation Criteria
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Eligibility Criteria
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Phase 1 Inclusion Criteria: Inclusion Criteria for Convalescent Plasma Donors: - Outpatients 18 years old and older who have recovered from COVID-19: Have proof of Original Positive SARS-CoV-2 NAT nasopharyngeal (NP) test result Complete resolution of symptoms at least 14 days prior to donation Negative SARS-CoV-2 NAT nasopharyngeal (NP) specimen at screening visit Able to meet standard criteria for blood donation Clinically stable based on provider assessment Phase 1 Exclusion Criteria: Exclusion criteria: Inability to complete or contraindication to donation based on Donor History - Questionnaire (DHQ), FDA approved standard blood donation form Hb<13.0 g/dL for males Hb<12.5 g/dL for females History of 3 more pregnancies unless HLA antibody testing is performed and deemed acceptable by director of blood donor services (to reduce risks of transfusion Related Acute Lung Injury in recipients). The presence of any transfusion transmitted diseases is based on history or test results from blood sample collected from the donor at time of plasma collection in accordance to standard practice. Female subjects who are pregnant by self-report. Receipt of pooled immunoglobulin in past 30 days PHASE 2: Inclusion Criteria for Recipients of COVID-19 Convalescent Plasma: Patients in the Inova Health System with confirmed COVID-19 by PCR testing Age ≥ 13 years Currently hospitalized with COVID-19 infection with severe or life-threatening clinical syndrome as follows: Severe COVID-19: (three or more of the following) Dyspnea Respiratory rate ≥ 30/min Blood oxygen saturation (SpO2) ≤ 94% on room air Partial pressure of arterial oxygen to fraction of inspired oxygen (P:F) ratio < 300 Pulmonary infiltrates > 50% of lung parenchyma within 24 to 48 hours Life-threatening disease is defined as: (one of the following) Respiratory failure Septic shock, and/or Multiple organ dysfunction or failure Patient must provide informed consent or have health care power of attorney/next of kin provide consent if he/she cannot. PHASE 2 Exclusion Criteria: Contraindication to receive plasma as deemed by the treating physician Severe hypercoagulable state (documented in medical chart or by treating physician assessment) Absolute IgA deficiency Prior history of Transfusion Related Acute Lung Injury (TRALI) Inability to tolerate plasma volume due to severe systolic or diastolic heart failure despite slower infusion and diuretic administration Positive pregnancy test (HCG)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1 will be recruitment and enrollment of plasma donors. Phase 2 will be continued recruitment and enrollment of plasma donors, with the addition of recruitment and enrollment of plasma recipients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recipient of COVID-19 Convalescent Plasma (CCP) Transfusion<br>Patients hospitalized with COVID-19 infection with severe or life-threatening clinical syndrome and meet eligibility criteria | Biological: Convalescent plasma transfusion<br>* Transfusion of COVID-19 convalescent plasma to participants currently hospitalized with COVID-19 infection with severe or life-threatening clinical syndrome.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change is Clinical Status | Change is clinical status as captured by 7-point ordinal scale to include Death Hospitalized, requiring mechanical ventilation or ECMO Hospitalized, requiring non-invasive ventilation or high flow oxygen Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen--requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen-not requiring ongoing medical care (COVID-19 related or otherwise). Not Hospitalized | Time of plasma infusion (day 0) compared to day 7 | 
| Transfusion Related Events Due to Administration of CCP | Number of participants with Transfusion Related Adverse Events | Within 6 hours of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change is Clinical Status | Change in 7-point ordinal scale score from time of plasma infusion (day 0-prior to first infusion) to days 7, 14, 21, and 28. 7 point ordinal scale: Death Hospitalized, requiring mechanical ventilation or ECMO Hospitalized, requiring non-invasive ventilation or high flow oxygen Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen--requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen-not requiring ongoing medical care (COVID-19 related or otherwise). Not Hospitalized | Time of plasma infusion (day 0 prior to first infusion) to days 7,14, 21, and 28 | 
| Length of Hospital Stay | Total duration of hospital stay which includes from Admission with COVID-19 from admission with COVID-19 symptoms to discharge or death (up to an average of 67 days) | Total Index Hospitalization | 
| Mechanical Ventilation | Number of participants that required mechanical ventilation that were not on mechanical ventilation at that time point. | Days 7, 14, 21, 28 | 
| Change in Mechanical Ventilation Status | Number of participants who required a change in the mechanical ventilation status | Day 0 (date of CCP transfusion) to Day 28 | 
| Mortality | All-cause Mortality | From Day of Transfusion (Day 0) to Day 28 post-transfusion for patients who received CCP. Patients who donated CCP were not followed for a defined time period after CCP donation. |