Trial Outcomes & Findings for CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) (NCT NCT04348656)

NCT ID: NCT04348656

Last Updated: 2022-03-03

Results Overview

Endpoint of the need for intubation or patient death

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

940 participants

Primary outcome timeframe

Day 30

Results posted on

2022-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	Convalescent Plasma \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care Treated as per institutional standard of care.
Overall Study STARTED	627	313
Overall Study Baseline Population	625	313
Overall Study Intention to Treat Analysis	614	307
Overall Study Per Protocol Analysis	548	303
Overall Study COMPLETED	614	307
Overall Study NOT COMPLETED	13	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Convalescent Plasma \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care Treated as per institutional standard of care.
Overall Study Withdrawal by Subject	2	0
Overall Study Lost to Follow-up	11	6

Baseline Characteristics

259 patients (171 in the convalescent plasma arm and 88 in the standard of care arm) had an unknown BMI and were not included in this analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Convalescent Plasma n=625 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=313 Participants Treated as per institutional standard of care.	Total n=938 Participants Total of all reporting groups
Age, Continuous	67.7 years STANDARD_DEVIATION 16.0 • n=625 Participants	67.1 years STANDARD_DEVIATION 14.8 • n=313 Participants	67.5 years STANDARD_DEVIATION 15.6 • n=938 Participants
Age, Customized >= 60 years	438 Participants n=625 Participants	218 Participants n=313 Participants	656 Participants n=938 Participants
Age, Customized < 60 years	187 Participants n=625 Participants	95 Participants n=313 Participants	282 Participants n=938 Participants
Sex: Female, Male Female	256 Participants n=625 Participants	128 Participants n=313 Participants	384 Participants n=938 Participants
Sex: Female, Male Male	369 Participants n=625 Participants	185 Participants n=313 Participants	554 Participants n=938 Participants
Race/Ethnicity, Customized White	305 Participants n=625 Participants	153 Participants n=313 Participants	458 Participants n=938 Participants
Race/Ethnicity, Customized Asian	104 Participants n=625 Participants	46 Participants n=313 Participants	150 Participants n=938 Participants
Race/Ethnicity, Customized Hispanic or Latino	34 Participants n=625 Participants	9 Participants n=313 Participants	43 Participants n=938 Participants
Race/Ethnicity, Customized Black	25 Participants n=625 Participants	11 Participants n=313 Participants	36 Participants n=938 Participants
Race/Ethnicity, Customized Other	38 Participants n=625 Participants	28 Participants n=313 Participants	66 Participants n=938 Participants
Race/Ethnicity, Customized Unknown	119 Participants n=625 Participants	66 Participants n=313 Participants	185 Participants n=938 Participants
Region of Enrollment Canada	529 Participants n=625 Participants	265 Participants n=313 Participants	794 Participants n=938 Participants
Region of Enrollment United States	89 Participants n=625 Participants	45 Participants n=313 Participants	134 Participants n=938 Participants
Region of Enrollment Brazil	7 Participants n=625 Participants	3 Participants n=313 Participants	10 Participants n=938 Participants
Pregnancy present at randomization	4 Participants n=625 Participants	1 Participants n=313 Participants	5 Participants n=938 Participants
ABO blood group O	270 Participants n=625 Participants	113 Participants n=313 Participants	383 Participants n=938 Participants
ABO blood group A	235 Participants n=625 Participants	121 Participants n=313 Participants	356 Participants n=938 Participants
ABO blood group B	89 Participants n=625 Participants	57 Participants n=313 Participants	146 Participants n=938 Participants
ABO blood group AB	31 Participants n=625 Participants	22 Participants n=313 Participants	53 Participants n=938 Participants
Body Mass Index	30.0 kg/m^2 STANDARD_DEVIATION 7.5 • n=454 Participants • 259 patients (171 in the convalescent plasma arm and 88 in the standard of care arm) had an unknown BMI and were not included in this analysis.	30.0 kg/m^2 STANDARD_DEVIATION 7.4 • n=225 Participants • 259 patients (171 in the convalescent plasma arm and 88 in the standard of care arm) had an unknown BMI and were not included in this analysis.	30.0 kg/m^2 STANDARD_DEVIATION 7.4 • n=679 Participants • 259 patients (171 in the convalescent plasma arm and 88 in the standard of care arm) had an unknown BMI and were not included in this analysis.
Body Mass Index BMI < 30 kg/m^2	256 Participants n=625 Participants	123 Participants n=313 Participants	379 Participants n=938 Participants
Body Mass Index BMI >= 30 kg/m^2	198 Participants n=625 Participants	102 Participants n=313 Participants	300 Participants n=938 Participants
Body Mass Index BMI Unknown	171 Participants n=625 Participants	88 Participants n=313 Participants	259 Participants n=938 Participants
Presence of comorbidity Diabetes	220 Participants n=625 Participants	108 Participants n=313 Participants	328 Participants n=938 Participants
Presence of comorbidity Cardiac disease	385 Participants n=625 Participants	197 Participants n=313 Participants	582 Participants n=938 Participants
Presence of comorbidity Baseline respiratory diseases	147 Participants n=625 Participants	79 Participants n=313 Participants	226 Participants n=938 Participants
Abnormal CT chest or chest x-ray result before randomization	563 Participants n=625 Participants	266 Participants n=313 Participants	829 Participants n=938 Participants
Medication for other research study at baseline	53 Participants n=625 Participants	41 Participants n=313 Participants	94 Participants n=938 Participants
Medication for COVID-19 at baseline Azithromycin	279 Participants n=625 Participants	137 Participants n=313 Participants	416 Participants n=938 Participants
Medication for COVID-19 at baseline Other antibiotics	405 Participants n=625 Participants	186 Participants n=313 Participants	591 Participants n=938 Participants
Medication for COVID-19 at baseline Systemic corticosteroids	496 Participants n=625 Participants	258 Participants n=313 Participants	754 Participants n=938 Participants
Medication for COVID-19 at baseline Antiviral medications	165 Participants n=625 Participants	80 Participants n=313 Participants	245 Participants n=938 Participants
Medication for COVID-19 at baseline Anticoagulants	355 Participants n=625 Participants	180 Participants n=313 Participants	535 Participants n=938 Participants
Medication for COVID-19 at baseline Other COVID-19 medications	79 Participants n=625 Participants	39 Participants n=313 Participants	118 Participants n=938 Participants
Medication not for COVID-19 at baseline Angiotensin-converting enzyme inhibitor	85 Participants n=625 Participants	63 Participants n=313 Participants	148 Participants n=938 Participants
Medication not for COVID-19 at baseline Angiotensin-converting enzyme receptor blocker	77 Participants n=625 Participants	47 Participants n=313 Participants	124 Participants n=938 Participants
Medication not for COVID-19 at baseline Non-steroidal anti-inflammatory drugs	77 Participants n=625 Participants	52 Participants n=313 Participants	129 Participants n=938 Participants
Medication not for COVID-19 at baseline Colchicine	5 Participants n=625 Participants	2 Participants n=313 Participants	7 Participants n=938 Participants
Medication not for COVID-19 at baseline Systemic corticosteroids	61 Participants n=625 Participants	35 Participants n=313 Participants	96 Participants n=938 Participants
Medication not for COVID-19 at baseline Inhaled corticosteroids	84 Participants n=625 Participants	42 Participants n=313 Participants	126 Participants n=938 Participants
Medication not for COVID-19 at baseline Immunomodulatory agents	22 Participants n=625 Participants	18 Participants n=313 Participants	40 Participants n=938 Participants
Medication not for COVID-19 at baseline Anticoagulants	135 Participants n=625 Participants	64 Participants n=313 Participants	199 Participants n=938 Participants
Systemic corticosteroid at baseline	504 Participants n=625 Participants	262 Participants n=313 Participants	766 Participants n=938 Participants
Fraction of inhaled oxygen (FiO2) at the time of randomization	49.5 percentage of oxygen STANDARD_DEVIATION 25.2 • n=625 Participants	48.8 percentage of oxygen STANDARD_DEVIATION 25.1 • n=313 Participants	49.3 percentage of oxygen STANDARD_DEVIATION 25.2 • n=938 Participants
Time from any symptom onset to randomization	8.0 days STANDARD_DEVIATION 3.8 • n=625 Participants	7.8 days STANDARD_DEVIATION 3.4 • n=313 Participants	7.9 days STANDARD_DEVIATION 3.7 • n=938 Participants
Time from COVID-19 diagnosis to randomization	4.9 days STANDARD_DEVIATION 3.6 • n=625 Participants	5.1 days STANDARD_DEVIATION 4.4 • n=313 Participants	5.0 days STANDARD_DEVIATION 3.9 • n=938 Participants
Location at time of randomization Ward	505 Participants n=625 Participants	260 Participants n=313 Participants	765 Participants n=938 Participants
Location at time of randomization Intensive care unit	120 Participants n=625 Participants	53 Participants n=313 Participants	173 Participants n=938 Participants
Enrolled in other clinical trials	168 Participants n=625 Participants	98 Participants n=313 Participants	266 Participants n=938 Participants

PRIMARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Endpoint of the need for intubation or patient death

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Number of Participants Who Were Intubated or Died	199 Participants	86 Participants

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Time in days from randomization to occurrence of intubation or death

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Time to Intubation or In-hospital Death	22.8 days Standard Deviation 11.0	23.4 days Standard Deviation 11.0

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Number of days off ventilator at 30 days

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Ventilator-free Days by Day 30	23.4 days Standard Deviation 10.4	24.0 days Standard Deviation 10.5

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Occurrence of patient death at 30 days

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Death by Day 30	141 Participants	63 Participants

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Number of days spent in the intensive care unit (ICU) over the 30-day period following randomization

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Length of Stay in Intensive Care Unit (ICU)	4.3 days Standard Deviation 7.9	3.7 days Standard Deviation 7.1

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available. Data from 11 patients on chronic kidney replacement therapy at baseline were not included in the Count of Participants since they were receiving renal replacement therapy prior to study entry and therefore do not meet our criteria for needing new renal replacement therapy during the study period.

Need for new renal replacement therapy

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Need for Renal Replacement Therapy	10 Participants	6 Participants

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Requirement for extracorporeal membrane oxygenation (ECMO)

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Need for Extracorporeal Membrane Oxygenation (ECMO)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

New diagnosis of myocarditis

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Development of Myocarditis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 90

Population: Baseline study population- all randomized patients, excluding 2 who withdrew consent prior to the intervention

Occurrence of death while in hospital, censored at 90 days. Patients who were still in hospital at Day 30 were followed until Day 90 to capture in-hospital mortality.

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=625 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=313 Participants Treated as per institutional standard of care.
In-hospital Death	156 Participants	69 Participants

SECONDARY outcome

Timeframe: Day 90

Population: Baseline study population (all randomized patients, excluding 2 who withdrew consent prior to the intervention)

Time to in-hospital death at 90 days. Patients who were still in hospital at Day 30 were followed until Day 90 to capture in-hospital mortality.

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=625 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=313 Participants Treated as per institutional standard of care.
Time to In-hospital Death	16.3 days Standard Deviation 17.1	14.8 days Standard Deviation 16.3

SECONDARY outcome

Timeframe: Day 90

Population: Baseline study population- all randomized patients, excluding 2 who withdrew consent prior to receiving the intervention

Number of days from randomization to death or hospital discharge. Patients still in hospital at Day 30 were followed until Day 90 to capture death or discharge from hospital.

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=625 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=313 Participants Treated as per institutional standard of care.
Length of Stay in Hospital	16.3 days Standard Deviation 17.1	14.8 days Standard Deviation 16.3

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on the primary outcome available

Number of participants with Grade 3 and 4 (CTCAE v4.0) serious adverse events, and cumulative incidence of Grade 3 and 4 serious adverse events (using MedDRA AE terms)

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Number of Participants With Grade 3 and 4 Serious Adverse Events	92 Participants	30 Participants

SECONDARY outcome

Timeframe: Day 30

Population: Only patients in the convalescent plasma (CCP) arm (intention to treat population) are assessed for CCP-related transfusion events, as these cannot occur in the standard of care arm.

Number of participants experiencing CCP transfusion-associated adverse events (AE), as defined by the International Society of Blood Tranfusion (ISBT ) classification

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care Treated as per institutional standard of care.
Number of Participants With CCP Transfusion-associated Adverse Events (AE)	35 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 30

Population: Intention to treat population with data on primary outcome available

Number of Participants with Grade 3-5 (CTCAE v4.0) serious adverse events reported to Day 30

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=614 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 Participants Treated as per institutional standard of care.
Number of Participants With Grade 3, 4, or 5 Serious Adverse Events	205 Participants	81 Participants

SECONDARY outcome

Timeframe: Baseline and Day 30

Population: Patients with a complete EQ-5D-5L at both baseline AND Day 30. Patients who were unable to complete the EQ-5D-5L due to their health status or other reason are excluded from this population. Proper administration of the EQ-5D-5L requires the answers be obtained directly from the patient.

Change in score on EQ-5D-5L instrument at Day 30 as compared to baseline. The EQ-5D-5L measures health-related quality of life in five dimensions, namely, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Patients can report five level impairment, reflecting no, slight, moderate, severe, and extreme problems in each dimension. The range of possible values is -0.148 to 0.949, with a higher score reflecting a better outcome. For the change in score, a positive number indicates that the scores improved from baseline.

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=272 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=157 Participants Treated as per institutional standard of care.
Patient Reported Outcome Using Change in EQ-5D-5L Score	0.150 units on a scale Standard Deviation 0.2588	0.157 units on a scale Standard Deviation 0.2859

SECONDARY outcome

Timeframe: Day 30

Population: Patients with a completed baseline EQ-5D-5L AND either a completed EQ-5D-5L at Day 30 or who were dead at Day 30. Patients who did not have a completed baseline EQ-5D-5L were excluded from this population.

Quality-adjusted life days calculated using the EQ-5D-5L score. Quality-adjusted life days is a measure of how well a patient lives for how long. It combines the length of life and quality of life into one value. This is calculated by multiplying the health utility (derived from the EQ-5D-5L score) by the amount of time the patient is alive during the study period. A higher number is better.

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=341 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=194 Participants Treated as per institutional standard of care.
Patient Reported Outcome- Quality-adjusted Life Days	17.959 quality adjusted life days Standard Deviation 9.0363	18.037 quality adjusted life days Standard Deviation 8.9771

SECONDARY outcome

Timeframe: Day 30

Population: Patients with a completed baseline EQ-5D-5L AND either a completed EQ-5D-5L at Day 30 or who were dead at Day 30. The cost results will be combined with the quality-adjusted life day results to calculate the incremental cost per quality-adjusted life day, so the analysis population matches that of the quality-adjusted life day analysis.

Cost per patient calculated using cost of the intervention and costs of the hospital stay

Outcome measures

Outcome measures
Measure	Convalescent Plasma n=341 Participants \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=194 Participants Treated as per institutional standard of care.
Cost of Intervention and Hospital Stay	23516.74 Canadian dollars Standard Deviation 21373.80	20025.05 Canadian dollars Standard Deviation 17957.57

Adverse Events

Convalescent Plasma

Serious events: 205 serious events

Other events: 110 other events

Deaths: 160 deaths

Standard of Care

Serious events: 81 serious events

Other events: 35 other events

Deaths: 70 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Convalescent Plasma n=614 participants at risk \~500 mL ABO compatible convalescent apheresis plasma Convalescent plasma: Patients will receive 500 mL of convalescent plasma (from one single-donor unit of 500 mL or 2 units of 250 mL from 1-2 donations) collected by apheresis from donors who have recovered from COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours. When administering 2 units of 250 mL, the 2nd unit will be administered after the first, and no longer than 12 hours later. The patient will be monitored for adverse events as per each site's policies.	Standard of Care n=307 participants at risk Treated as per institutional standard of care.
Investigations Lymphocyte count decreased	2.8% 17/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	2.6% 8/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.9% 18/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	2.0% 6/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Infections and infestations Infections and infestations, other	2.1% 13/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	2.3% 7/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Metabolism and nutrition disorders Hyperglycemia	2.1% 13/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	1.6% 5/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Blood and lymphatic system disorders Anemia	2.3% 14/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	0.98% 3/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Vascular disorders Hypertension	1.8% 11/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	0.65% 2/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Metabolism and nutrition disorders Hypermagnesemia	1.5% 9/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	0.33% 1/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Metabolism and nutrition disorders Hypophosphatemia	1.3% 8/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	0.33% 1/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.
Infections and infestations Urinary tract infection	1.1% 7/614 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.	0.65% 2/307 • AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30). MedDRA 12.1 was used for AE terminology jointly with CTCAE v4.0 for AE severity grading. Serious and Other (Not Including Serious) Adverse Events assessed for the Intention to Treat Population and All-Cause Mortality assessed for the Baseline Population. The number of deaths reported under "all cause mortality" include all reported deaths prior to Day 30, plus any in-hospital deaths occurring up to Day 90 in patients who were still in hospital at Day 30.

Additional Information

Dr Donald Arnold

McMaster University/Hamilton Health Sciences

Phone: 905 525 9140

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place