Coronavirus, Coronavirus Infection, COVID
Conditions
Keywords
COVID-19
Brief summary
Pilot study of tolerability and efficacy of transfusion of 200mL of convalescent plasma in patients with COVID-19 respiratory disease.
Detailed description
Importance: Convalescent plasma has been shown to be safe in patients with COVID-19, but whether it is clinically effective in patients with severe COVID-19 pneumonia is still unclear. Objective: To evaluate the safety, tolerability, efficacy, and adverse events related to transfusion of convalescent plasma in patients hospitalized with severe or critical COVID-19 pneumonia. Design, Setting and Participants: Randomized, single center, open-label, controlled trial of patients hospitalized between May 1, 2020, and August 1, 2020, with severe COVID-19 pneumonia in 1 tertiary care health system in the United States. A total of 30 participants age ≥ 18 years with 1 or more of the following were enrolled: dyspnea; respiratory rate \> 30; O2 saturation ≤ 93%; PaO2/FiO2 or SaO2/FiO2 ratio \< 300 mm Hg; and bilateral airspace opacities on chest x-ray \> 50% within 24 to 48 hours. Intervention: Transfusion with 1 unit of ABO compatible convalescent plasma in addition to standard care (n = 20) or standard care (n = 10). Standard care included steroids. Main Outcomes and Measures: Primary outcome was improvement in oxygenation 72 hours after infusion measured by change in arterial blood gas or in PaO2/FiO2 or Sa/FiO2. Secondary outcomes were mortality at 28 days, days on mechanical ventilation, intensive care unit and hospital length of stay, and mSOFA score.
Interventions
BIOLOGICALConvalescent plasma
One 200mL transfusion of ABO compatible convalescent plasma over 3 hours
Sponsors
Henry Ford Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized control trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age \> 18 with one or more of the following: Dyspnea Respiratory rate \>= 30 breaths/min Oxygen saturation \<=93% PaO2/FiO2 \<300 Bilateral airspace opacities on chest radiograph at 24 to 48 hours
Exclusion criteria
* Acute myocardial infarction in past 30 days Acute stroke in past 30 days VV ECMO VA ECMO
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Respiratory Disease Severity | day 3 post transfusion | Change in oxygenation as documented by SaO2/FiO2 at 72 hours after infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay | Up to 60 days At the end of the trial, if patients were still in the hospital, their date of transfer out of the hospital was collected and hospital length of stay calculated. | Hospital length of stay |
| Ventilator Days | 28 day | Duration of time on ventilator |
| ICU Length of Stay | Up to 60 days At the end of the trial, if patients were still in the ICU, their date of transfer out of the ICU was collected and total ICU length of stay calculated. | Total ICU length of stay |
| Normal Chest X Ray at 28 Days | 28 days | Change in Chest X Ray Findings |
| All-cause Mortality | 28 days | All-cause overall deaths at end of trial at 28 days |
| Number of Participants With Transfusion Adverse Events | From transfusion up to 1 day post-transfusion | Adverse transfusion events after 1 unit of convalescent plasma |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Convalescent Plasma Intervention Convalescent plasma 200mL transfusion
Convalescent plasma: One 200mL transfusion of ABO compatible convalescent plasma over 3 hours | 20 |
| Standard Therapy Control Standard therapy for COVID-19 disease as defined by institutional protocols | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Standard Therapy Control | Total | Convalescent Plasma Intervention |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 22 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 8 Participants | 5 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 13.6 | 55 years STANDARD_DEVIATION 13 | 56.6 years STANDARD_DEVIATION 13.9 |
| Bilateral airspace opacities on CXR >50% within 24 to 48 hours | 8 Participants | 23 Participants | 15 Participants |
| Dyspnea with Respiratory Rate (RR) >30 | 4 Participants | 13 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 16 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Mechanical ventilation | 5 Participants | 16 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 16 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 5 Participants | 8 Participants | 3 Participants |
| Region of Enrollment United States | 10 participants | 30 participants | 20 participants |
| SaO2/FiO2 | 196.5 ratio STANDARD_DEVIATION 89.9 | 190 ratio STANDARD_DEVIATION 90 | 188.4 ratio STANDARD_DEVIATION 96 |
| Sex: Female, Male Female | 4 Participants | 13 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 17 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 20 | 2 / 10 |
| other Total, other adverse events | 0 / 20 | 0 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 |
Outcome results
Primary
Change in Respiratory Disease Severity
Change in oxygenation as documented by SaO2/FiO2 at 72 hours after infusion
Time frame: day 3 post transfusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Convalescent Plasma Intervention | Change in Respiratory Disease Severity | 251 ratio | Standard Deviation 89 |
| Standard Therapy Control | Change in Respiratory Disease Severity | 276 ratio | Standard Deviation 188 |
Secondary
All-cause Mortality
All-cause overall deaths at end of trial at 28 days
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma Intervention | All-cause Mortality | 3 Participants |
| Standard Therapy Control | All-cause Mortality | 2 Participants |
Secondary
ICU Length of Stay
Total ICU length of stay
Time frame: Up to 60 days At the end of the trial, if patients were still in the ICU, their date of transfer out of the ICU was collected and total ICU length of stay calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Plasma Intervention | ICU Length of Stay | 19.5 days |
| Standard Therapy Control | ICU Length of Stay | 13 days |
Secondary
Length of Stay
Hospital length of stay
Time frame: Up to 60 days At the end of the trial, if patients were still in the hospital, their date of transfer out of the hospital was collected and hospital length of stay calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Plasma Intervention | Length of Stay | 20 days |
| Standard Therapy Control | Length of Stay | 11.5 days |
Secondary
Normal Chest X Ray at 28 Days
Change in Chest X Ray Findings
Time frame: 28 days
Population: Normal CXR at 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma Intervention | Normal Chest X Ray at 28 Days | 9 Participants |
| Standard Therapy Control | Normal Chest X Ray at 28 Days | 3 Participants |
Secondary
Number of Participants With Transfusion Adverse Events
Adverse transfusion events after 1 unit of convalescent plasma
Time frame: From transfusion up to 1 day post-transfusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Convalescent Plasma Intervention | Number of Participants With Transfusion Adverse Events | 0 participants |
| Standard Therapy Control | Number of Participants With Transfusion Adverse Events | 0 participants |
Secondary
Ventilator Days
Duration of time on ventilator
Time frame: 28 day
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Plasma Intervention | Ventilator Days | 15.6 days |
| Standard Therapy Control | Ventilator Days | 4.2 days |