Convalescent Plasma, COVID-19, SARS-CoV 2
Conditions
Keywords
COVID-19, anti SARS-CoV-2 convalescent plasma, COVID-19 convalescent plasma
Brief summary
Administration of convalescent plasma obtained from donors with prior documented SARS-CoV-2 infection
Detailed description
There are currently no proven therapeutic options for coronavirus disease (COVID-19), the infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human convalescent plasma is an option for treatment of COVID-19. Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1, MERS and H1N1 shows that convalescent plasma can be effective. Convalescent plasma will be obtained by plasmapheresis or regular whole blood donation in subjects who recovered from COVID-19 and who are otherwise eligible for donation according to the Institutional protocol. Recipients will be COVID-19 patients requiring hospitalization. A blood-type matched transfusion of convalescent plasma will be infused and recipients will be followed up.
Interventions
BIOLOGICALanti-SARS-CoV-2 convalescent plasma
Administration of convalescent plasma obtained from donors with prior documented SARS-CoV-2 infection
Sponsors
University Clinic for Infectious Diseases, North Macedonia
Institute for Transfusion Medicine of RNM
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Blood donors: 1. Age: \>18 and \<60 years 2. Body weight : \>55 kg 3. Confirmed previous SARS CoV-2 infection 4. Minimum 28 days after the last symptom or finishing of the isolation, or 5. 21 day without symptoms from the date of the negative SARS CoV-2 test 6. Written informed consent to participate in this clinical trial, to donate plasma and to store the specimen for future testing. 7. Concentration of COVID-19 IgG antibodies more than 5 AU/ml (Because measurement of neutralizing antibody titers is not available now, storing of retention sample from the convalescent plasma donation is performed for determining antibody titers at a later date) 8. Male donors, or female donors who have not been pregnant, or female donors who have been pregnant tested negative for HLA antibodies 9. Individuals who meet all regular voluntary donor eligibility requirements Patients/recipients: 1. Age: \>18 years 2. Admitted to an acute care facility for the treatment of COVID-19 complications 3. Patients with severe or immediately life-threatening COVID-19, or 4. Patients who are judged by a healthcare provider to be at high risk of progression to severe or life-threatening disease. 5. Informed consent provided by the patient or healthcare proxy
Exclusion criteria
Blood donors: 1. Age : \<18 or \>60 years 2. Female subjects who are pregnant 3. HIV1,2 hepatitis B,C or syphilis infection 4. Donors ineligible for regular voluntary blood donation Patients/recipients: 1. Age : \<18 years 2. Contraindication to transfusion (severe volume overload, history of anaphylaxis to blood products) 3. Patients who received in the past 30 days immunoglobulin therapy 4. Females who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay (LOS) | 28 days after transfusion or until hospital discharge (whichever comes first) | Total number of days patients were admitted to the hospital after convalescent plasma transfusion. |
| Number of Participants With Oxygenation Free Days | 28 days after transfusion or until hospital discharge (whichever comes first) | Number of participants without oxygenation support after receiving convalescent plasma |
| Number of Participants With Serious Adverse Events | 28 days after transfusion or until hospital discharge (whichever comes first) | Number of participants with serious adverse events during the study protocol |
| Duration of Oxygenation Support | 28 days after transfusion or until hospital discharge (whichever comes first) | The total number of days patients required respiratory support. |
| ICU Admission | 28 days after transfusion or until hospital discharge (whichever comes first) | Total number of subjects to be admitted to the ICU after the convalescent plasma transfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Different Clinical Outcomes Including Death, Critical Illness and Recovery | 28 days after transfusion or until hospital discharge (whichever comes first) | Number of participants with different clinical outcomes including death, critical illness, limitation of activities and recovery |
| Type of Respiratory Support | 28 days after transfusion or until hospital discharge (whichever comes first) | Type of supplemental oxygen support (e.g. nasal canula, high flow nasal canula, noninvasive ventilation, intubation and invasive mechanical ventilation, rescue ventilation) |
Countries
North Macedonia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hospitalized Patients With SARS CoV-2 Infection Hospitalized patients with SARS CoV-2 infection will receive an anti SARS-CoV-2 convalescent plasma
anti-SARS-CoV-2 convalescent plasma: Administration of convalescent plasma obtained from donors with prior documented SARS-CoV-2 infection | 189 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Transfer from/to other hospital | 8 |
Baseline characteristics
| Characteristic | Hospitalized Patients With SARS CoV-2 Infection |
|---|---|
| ABO blood type A | 94 Participants |
| ABO blood type AB | 16 Participants |
| ABO blood type B | 32 Participants |
| ABO blood type O | 47 Participants |
| Age, Continuous | 57.4 years STANDARD_DEVIATION 12.8 |
| Age, Customized 18-35 years | 11 Participants |
| Age, Customized 36-45 years | 23 Participants |
| Age, Customized 46-55 years | 47 Participants |
| Age, Customized 56-65 years | 56 Participants |
| Age, Customized 66-75 years | 41 Participants |
| Age, Customized more than 75 years | 11 Participants |
| Body Mass Index 18.5-24.9 kg/m^2 (normal) | 37 Participants |
| Body Mass Index 25-29.9 kg/m^2 (overweight) | 95 Participants |
| Body Mass Index equal or more than 30 kg/m^2 (obese) | 57 Participants |
| Body Mass Index | 28.4 kg/m^2 STANDARD_DEVIATION 4.4 |
| Comorbidities no | 55 Participants |
| Comorbidities yes | 134 Participants |
| Race/Ethnicity, Customized Ethnicity Albanians | 36 Participants |
| Race/Ethnicity, Customized Ethnicity Macedonians | 139 Participants |
| Race/Ethnicity, Customized Ethnicity others | 14 Participants |
| Region of Enrollment North Macedonia | 189 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 148 Participants |
| WHO progression score WHO disease progression score 3 - hospitalized patients without oxygen support | 65 Participants |
| WHO progression score WHO progression score 4 - hospitalized patients with oxygen support (nasal canila, oxygen mask) | 65 Participants |
| WHO progression score WHO progression score 5 - hospitalized with high-flow oxygen support (noninvasive ventilation) | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 189 |
| other Total, other adverse events | 1 / 189 |
| serious Total, serious adverse events | 0 / 189 |
Outcome results
Primary
Duration of Oxygenation Support
The total number of days patients required respiratory support.
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
Population: This is the number of patients that required respiratory support before CCP transfusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | Duration of Oxygenation Support | 7.4 days | Standard Deviation 5.2 |
Primary
Hospital Length of Stay (LOS)
Total number of days patients were admitted to the hospital after convalescent plasma transfusion.
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
Population: The bellow are shown subgroups of participants according to the WHO disease progression scores 3,4 and 5, which all together comprises total investigated group of 189 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | Hospital Length of Stay (LOS) | total investigated group | 11.0 days | Standard Deviation 5.3 |
| Hospitalized Patients With SARS CoV-2 Infection | Hospital Length of Stay (LOS) | patients with WHO disease progression score 3, which are not on oxygen support | 8.6 days | Standard Deviation 2.7 |
| Hospitalized Patients With SARS CoV-2 Infection | Hospital Length of Stay (LOS) | patients with WHO score 4, which are on oxygen support with nasal canila or oxygen mask | 11.1 days | Standard Deviation 4.7 |
| Hospitalized Patients With SARS CoV-2 Infection | Hospital Length of Stay (LOS) | patients with WHO score 5, which are on oxygen support with noninvasive ventilation | 13.6 days | Standard Deviation 6.7 |
p-value: 0.05ANOVA
Primary
ICU Admission
Total number of subjects to be admitted to the ICU after the convalescent plasma transfusion.
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | ICU Admission | 1 Participants |
Primary
Number of Participants With Oxygenation Free Days
Number of participants without oxygenation support after receiving convalescent plasma
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Oxygenation Free Days | Participants with oxygenation free days at discharge | 167 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Oxygenation Free Days | Participants with oxygenation free days before CCP transfusion | 65 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Oxygenation Free Days | Participants with oxygenation free days 24 hours after CCP transfusion | 76 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Oxygenation Free Days | Participants with oxygenation free days after 7 days after transfusion | 103 Participants |
Primary
Number of Participants With Serious Adverse Events
Number of participants with serious adverse events during the study protocol
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Serious Adverse Events | 0 Participants |
Secondary
Number of Participants With Different Clinical Outcomes Including Death, Critical Illness and Recovery
Number of participants with different clinical outcomes including death, critical illness, limitation of activities and recovery
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Different Clinical Outcomes Including Death, Critical Illness and Recovery | total recovery | 164 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Different Clinical Outcomes Including Death, Critical Illness and Recovery | recovery with limitation of activities | 3 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Number of Participants With Different Clinical Outcomes Including Death, Critical Illness and Recovery | death | 22 Participants |
Comparison: Overall survival between the three WHO score groups 3, 4 and 5p-value: 0.05Chi-squared
Comparison: Correlation of mortality versus WHO disease progression score of patientsp-value: 0.05Chi-squared
Comparison: Correlation of mortality versus stay in the intensive care unit (ICU)p-value: 0.05Chi-squared
Secondary
Type of Respiratory Support
Type of supplemental oxygen support (e.g. nasal canula, high flow nasal canula, noninvasive ventilation, intubation and invasive mechanical ventilation, rescue ventilation)
Time frame: 28 days after transfusion or until hospital discharge (whichever comes first)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Nasal canula, oxygen mask before CCP transfusion | 65 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Nasal canula, oxygen mask 24 hours after CCP transfusion | 56 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Nasal canula, oxygen mask 7 days after CCP transfusion | 35 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Noninvasive ventilation, high flow nasal canula before CCP transfusion | 59 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Noninvasive ventilation, high flow nasal canula 24 hours after CCP transfusion | 56 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Noninvasive ventilation, high flow nasal canula 7 days after CCP transfusion | 25 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Intubation or invasive mechanical ventilation, before CCP transfusion | 0 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Intubation or invasive mechanical ventilation, 24 hours after CCP transfusion | 1 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Intubation or invasive mechanical ventilation, 7 days after CCP transfusion | 1 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Rescue ventilation before CCP transfusion | 0 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Rescue ventilation 24 hours after CCP transfusion | 0 Participants |
| Hospitalized Patients With SARS CoV-2 Infection | Type of Respiratory Support | Rescue ventilation 7 days after CCP transfusion | 1 Participants |