Coronavirus, Coronavirus Infection, COVID19, RNA Virus Infections, Virus Diseases
Conditions
Keywords
Covid19, Covid 19, Convalescent Plasma, SARS-CoV-2, Pediatric, Pediatrics
Brief summary
This is a prospective study, using plasma to help fight off infections of those suffering from COVID-19 in accordance with collection guidelines for plasma and FDA IND requirements. This study included up to 240 participants potentially receiving convalescent plasma. NOTE: West Virginia does not have any entity with the required FDA registration/licensure or necessary equipment to collect convalescent plasma for transfusion. Therefore, the plasma donation portion of this study was not completed.
Detailed description
Convalescent plasma (here on referred to as plasma) has been used in emergency life-threatening situations to treat infections for over 100 years. The plasma is donated by an individual that has recovered from the very same infection that another person is infected with. This plasma is enriched in the antibodies that recognize and helped the body's immune system fight off the infection. When transfused from donor to recipient those antibodies will aid the recipient in fighting off the infection. In recent history this has been used to fight Ebola. Recently, the Federal Food and Drug Agency (FDA) made possible expedited Investigational New Drug (IND) process for plasma use in the fight against COVID19 for emergency and lifesaving uses. There are several other investigational drugs for treatment of COVID19 such as: Remdesivir, an antiviral. The off-label use of hydroxychloroquine, Lopinavir/ritonavir, or Tocilizumab have been authorized. Convalescent plasma mechanism of action helps to promote health by working with one's own immune system and will not interfere with the other proposed medications. It also will not weaken the immune system as the investigational and off label medications have the potential to do. Convalescent plasma is time honored and although investigational for each use against novel or rare infections, it is the basis for IgG infusions in the immunodeficient populations. Currently the use of IgG infusions such as Intravenous IgG (IVIG) is assumed to not have the right antibodies from donors in the general public. This is secondary to the novel nature of the COVID19 and the fact that the IVIG available today was collected 6 to 12 months ago from plasma donors; prior to the COVID19's outbreak discovery in China. It is for that reason that IVIG is not recommended at this time and the FDA has made special fast-tracking announcements for plasma use for COVID19. Currently, plasma is the only treatment that has a previous history of success in these novel or rare viral outbreak situations. It has already been reported to have been associated with survival of 5 out of 5 participants in a pilot study in China For the purpose of this study advanced respiratory support will include any measure of respiratory support above low flow nasal cannula oxygen (2 Liters/minute flow rate). For the purpose of this study dyspnea will be defined as any shortness of breath that is not completely relieved with the use of low flow nasal canula oxygen set to 2 Liters/minute flow rate and/or requiring breathing treatments such as but not limited to: bronchodilators more than every 4 hours to relieve symptoms. In the event that more than one recipient is identified and plasma is available in less than the total number of approved recipients, priority will be given to those approved by the FDA for the IND use of plasma for severe or critical condition. If there still exists a deficit of plasma, the priority will be given to those on advanced respiratory support with the most critical settings (if unclear then will be considered a tie); active pressor treatments; age \<1 years of age with days of life, age adjusted for prematurity as a tie breaker; age \>60 with years as a tie breaker; and lastly lottery pull with potential remaining recipients as the final tie breaker.
Interventions
BIOLOGICALConvalescent Plasma
1 to 2 units given over 4-6 hours. A unit will consist of about 200mL for both pediatric and adult populations. An additional unit of plasma will be given every 3 days up to 8 units if patient was not improving or getting worse. All pediatric patients will receive 10 mL/kg (1 dose) if moderate with concern for rapid progression up to 1 Unit; 10 mL/kg up to 2 units if severe or critical.
Sponsors
West Virginia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
31 Days to No maximum
Healthy volunteers
No
Inclusion criteria
(NOTE: It is important to note that West Virginia, as a state, does not have any entity with the required FDA registration or licensure, nor the necessary on-site equipment, to collect convalescent plasma for the purpose of plasma transfusion. Therefore, the plasma donation portion of this study was not completed). * Plasma donation: 1. Prior diagnosis of COVID-19 documented by a laboratory test 1. Abbott RealTime SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) test on the Abbott m2000 System (Inpatient WVU testing) 2. Other testing methods and vendors using FDA approved detection methods of SARS-CoV-2 under the Emergency Use Authorization (EUA) 2. Complete resolution of symptoms at least 28 days prior to donation 3. Complete resolution of symptoms for at least 14 days with negative repeat COVID-19 testing approved by the FDA EUA 4. Female donors age 18+ that have never been pregnant or negative for HLA antibodies 5. Male donors age 18+ 6. Negative results for COVID-19 either from one or more nasopharyngeal swab specimens or by a molecular diagnostic test from blood. A partial list of available tests can be accessed at https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations. 7. Defined SARS-CoV-2 neutralizing antibody titers, if testing can be conducted (e.g., of at least 1:1602, 1:360 up to 1:640 is preferred. In shortage case 1:80 is acceptable) 8. At least or greater than 50kg of weight * Plasma Recipients: 1. Individuals of any age above 30 days of life, sex, or pregnancy status suffering from confirmed COVID19 and in rapid progression, severe or critical condition meeting the FDA IND guidelines. 2. Must have laboratory confirmed COVID19 3. Must have severe or immediately life-threatening COVID19 4. Must provide informed consent/assent
Exclusion criteria
* Plasma donation: 1. Individuals that do not meet the requirement from the American Red Cross for plasma donation or equivalent 2. Individuals plasma that has not passed safety screening after procurement by the American Red Cross for plasma donation or equivalent * Plasma Recipients 1. Individuals with COVID19 who are not in clinical concern for rapid progression, severe or critical condition 2. Individuals who are in critical condition that are not confirmed to have COVID19 3. Individuals with known Selective IgA Deficiency, that has not been found to be absent of anti-IgA antibodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time of Meeting Infusion Criteria to Infusion | up to 30 days | Time from meeting protocol-specified infusion criteria to the start of convalescent plasma infusion, measured in days. |
| Plasma Recipient Survival | 30 days from discharge | Number of participants who were alive 30 days after hospital discharge. |
| Identify Plasma Donor | 365 days | Time it takes to identify eligible donors whom are willing to donate. Measured in days for 365 days |
| Outreach to Plasma Donor | 365 days | Time it takes the plasma collection center to contact willing donors whom are allowed to donate plasma Measured in days for 365 days |
| Plasma Donor Time Until Donated | up to 1 year | Time until plasma is donated Measured every 24 hours up to 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Recipient Mortality | Up to 1 year | Number of mortalities within those that enrolled in the study. |
| Plasma Recipient LOS | up to 1 year | Length of Stay in hospital. Measured every day until patient discharged from hospital up to 1 year |
| Plasma Recipient AE (Day 1) | Day 1 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 1) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 2) | Day 2 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 2) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 3) | Day 3 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 3) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 4) | Day 4 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 4) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 5) | Day 5 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 5) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 6) | Day 6 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 6) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 7) | Day 7 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 7) post infusion. \[Safety and Tolerability\] |
| Plasma Recipient AE (Day 30) | Day 30 | Number of treatment-emergent adverse events recorded among recipients on this study day (Day 30) of follow up post infusion \[Safety and Tolerability\] |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrian Peppers, DO, PhD
WVU Medicine Children's
Participant flow
Recruitment details
Recipients were hospitalized patients who received convalescent plasma under protocol-defined eligibility criteria during the COVID-19 pandemic period.
Pre-assignment details
This study enrolled plasma recipients only. No plasma donors were enrolled as study participants. West Virginia does not have a single entity with FDA registration/licensure and the required on-site equipment to collect convalescent plasma for transfusion. Although donor-related operational steps were included in the initial protocol, donor recruitment and collection were not performed. Stored convalescent plasma from external suppliers was used.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65 years |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 117 |
| other Total, other adverse events | 34 / 117 |
| serious Total, serious adverse events | 16 / 117 |
Outcome results
None listed