CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1)

• Sponsor: Hamilton Health Sciences Corporation (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04348656
• Collaborator: Canadian Blood Services (Other), Héma-Québec (Other), University of Toronto (Other), Université de Montréal (Other), Weill Medical College of Cornell University (Other), New York Blood Center (Other)
• Enrollment: 940
• Locations: 73
• Arms: 2
• Actual Duration (Months): 15.1
• Patients Per Site: 12.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

There is currently no treatment available for COVID-19, the acute respiratory illness caused by the novel SAR-CoV-2. Convalescent plasma from patients who have recovered from COVID-19 that contains antibodies to the virus is a potential therapy. On March 25th, 2020, the FDA approved the use of convalescent plasma under the emergency investigational new drug (eIND) category. Randomized trials are needed to determine the efficacy and safety of COVID-19 convalescent plasma for acute COVID-19 infection.

The objective of the CONCOR-1 trial is to determine the efficacy of transfusion of COVID-19 convalescent plasma to adult patients admitted to hospital with COVID-19 infection at decreasing the frequency of in-hospital mortality in patients hospitalized for COVID-19.

It is hypothesized that treating hospitalized COVID-19 patients with convalescent plasma early in their clinical course will reduce the risk of death, and that other outcomes will be improved including risk of intubation, and length of ICU and hospital stay.

This pan-Canadian clinical trial has the potential to improve patient outcomes and reduce the burden on health care resources including reducing the need for ICU beds and ventilators.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: Convalescent plasma	Phase 3

Detailed Description

Problem to be addressed: In December 2019, the Wuhan Municipal Health Committee (Wuhan, China) identified an outbreak of viral pneumonia cases of unknown cause. Coronavirus RNA was quickly identified in some of these patients.This novel coronavirus has been designated SARS-CoV-2, and the disease caused by this virus has been designated COVID-19.Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise [1] in many countries over the coming weeks to months.Global efforts to evaluate novel antivirals and therapeutic strategies to treat COVID-19 have intensified. There is an urgent public health need for rapid development of novel interventions. At present, there is no specific antiviral therapy for coronavirus infections.

Passive immunization:Passive immunization consists in the transfer of antibodies from immunized donor to non-immunized individual in order to transfer transient protection against an infective agent. A physiological example of passive immunization is the transfer of maternal IgG antibodies to the foetus through the placenta to confer humoral protection to newborns in the first years of life. Passive immunization differs from active immunization in which the patient develops their own immune response following contact with the infective agent or vaccine.

Known potential risks and benefits: There is a theoretical risk of antibody-dependent enhancement of infection (ADE) through which virus targeted by non-neutralizing antibodies gain entry into macrophages. Another theoretical risk is that antibody administration to those exposed to SARS-CoV-2 may avoid disease but modify the immune response such that those individuals mount attenuated immune responses, which would leave them vulnerable to subsequent re-infection. Finally, there are risks associated with any transfusion of plasma including transmission of blood transmitted viruses (e.g. HIV, HBV, HCV, etc.), allergic transfusion reactions, including anaphylaxis, febrile non hemolytic transfusion reaction, transfusion related acute lung injury (TRALI), transfusion associated cardiac overload (TACO), and hemolysis should ABO incompatible plasma be administered. Potential benefits of COVID-19 convalescent plasma include improved survival, improvement in symptoms, decreased risk in intubation for mechanical ventilation, decrease risk of intensive care unit (ICU) admission, shortened hospitalization time and suppression of viral load.

Mechanism of action: Transfusion of apheresis frozen plasma (AFP) from COVID-19 convalescent patients allows the transfer of donor neutralizing antibodies directed against SARS-CoV2 antigens to the recipient, thus allowing the generation of passive immunization. Naturally produced human antibody are polyclonal, meaning they are directed against a variety of different viral antigens and epitopes allowing for a general neutralizing effect against the virus rather than focussing on a specific target. Administration of convalescent plasma has been associated with rapid decrease in viral load. It is also possible that passive immunization contributes to improved cell-mediated immunity by favoring the phagocytosis and presentation of viral antigens to host T cells.

Participant recruitment:Only hospitalized COVID-19 patients are eligible so recruitment efforts will be focused on identified consecutive patients admitted to hospital with acute COVID-19 infection. No other external recruitment efforts are planned. At each participating hospital, a process for identifying patients with COVID-19 will be established.

Donor recruitment for Canadian sites: Recovered COVID-19 patients will be identified as potential donors in collaboration with provincial public health services, local health authorities, and individual co-investigators involved in the study. Potential donors may also be recruiting following self-identification on the routine donor questionnaire or through social media. They will be contacted by phone and invited to participate in the program as potential donors. After obtaining verbal consent and reviewing donor selection criteria, eligible participants will be directed to a Héma-Québec collection or Canadian Blood Services apheresis collection site in their area to donate.

Criteria for donors: All donors will need to meet the criteria set forth in the Manual of donor selection criteria in use at Héma-Québec or Canadian Blood ServicesIn addition, donors will require:

• Prior diagnosis of COVID-19 documented by a PCR test at time of infection or by positive anti-SARS-CoV-2 serology following infection

• Male donors, or female donors with no pregnancy history or with negative anti-HLA antibodies

• At least 6 days since last plasma donation

• Provided informed consent

• A complete resolution of symptoms at least 14 days prior to donation

Donor recruitment for United States sites: Recovered COVID-19 patients are being recruited through the New York Blood Center and Weill Cornell Medicine in separate protocols. Potential donors can self-refer via websites but also be referred by physicians or identified via the medical record system. Only donors with laboratory-confirmed history of COVID-19 will be screened. After providing consent and reviewing FDA and NYBC donor eligibility criteria, donors are screened for the presences of SARS-CoV-2 virus in the nasopharynx if screening within 14 days of complete resolution in accordance with current FDA guidance. Criteria for donation are subject to change based on future revision of FDA guidance. Those found to be eligible will be referred to NYBC for donation.

Criteria for donors:

• Provision of informed consent

• Aged 18 to 70 years. Donors are not longer eligible after their 71st birthday.

• Documented molecular diagnosis of SARS-CoV-2 by RT-PCR by nasopharyngeal swab, oropharyngeal swab, or sputum or detection of anti-SARS-CoV-2 IgG in serum.

• Complete resolution of COVID-19 symptoms at least 14 days prior to donation

• Not currently pregnant or pregnant within 6 weeks by self-report

• Male donors, or females with no pregnancy history or with negative anti-HLA antibodies

• Meets blood donor criteria specified by NYBC, which is consistent with FDA regulations.

Donors will be allowed to donate every 7 days. The following information will be collection from donors: ABO group, sex, age, date of onset of symptoms (when available), date of resolution of symptoms (when available), CCP collection date(s).

Randomization procedures: Patients will be randomized in a 2:1 ratio (convalescent plasma vs standard of care). Patients will be randomized using a secure, concealed, computer-generated, web-accessed randomization sequence. Randomization will be stratified by centre and age (<60 and ≥ 60 years). Within each stratum, variable permuted block sized will be used. This approach will ensure that concealment of the treatment sequence is maintained.

Duration of follow-up: Subjects will be followed daily until hospital discharge or death. Patients discharged from hospital before Day 30 will be contacted by telephone on Day 30 ± 3 days to ascertain any AEs, vital status (dead/alive), hospital readmission and need for mechanical ventilation after discharge. Patients discharged from hospital will be contacted at Day 90+/- 7 days to determine vital status. Patients with a prolonged hospital admission will be censored at Day 90. The local study coordinator will collect all study data and record the data in the electronic CRF or paper CRF as per study procedures for each site.

Duration of study: For an individual subject, the study ends 90 days after randomization. The overall study will end when the last randomized subject has completed 90 day follow-up. We estimate that all patient will be enrolled in a period of 6 months, data on the primary endpoint will be available 30 days after last patient enrollment and data on all secondary endpoints will be available after 90-day from last patient enrollment.

Sample size considerations: Assuming a baseline risk of intubation or death of 30% in hospitalized patients with standard of care, a sample size of 1200 (800 in the convalescent plasma arm, and 400 in the standard of care arm) would provide 80% power to detect a relative risk reduction of 25% with convalescent plasma therapy using a 2-tailed test at level α = 0.05 and a 2:1 randomization.

Interim analysis: A single interim analysis is planned when the primary outcome (intubation or mortality at 30 days) is available for 50% of the target sample. An O'Brien-Fleming stopping rule will be used at that time, but treated as a guideline, so there is minimal impact on the threshold for statistical significance for the final significance test of the primary outcome. A DSMB will monitor ongoing results to ensure patient well-being and safety as well as study integrity. The DSMB will be asked to recommend early termination or modification only when there is clear and substantial evidence of a treatment difference.

Final analysis plan: The primary analysis will be based on the intention-to-treat population which will include data from all individuals who have been randomized. Outcomes will be attributed to the arm to which individuals were randomized irrespective of whether they received the planned intervention (e.g. plasma from a convalescent COVID-19 donor).

Study Design

• Study Type: Interventional
• Actual Enrollment: 940 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Open-Label Trial of CONvalenscent Plasma for Hospitalized Adults With Acute COVID-19 Respiratory Illness (CONCOR-1)
• Actual Study Start Date: Mar 14, 2020
• Actual Primary Completion Date: Mar 5, 2021
• Actual Study Completion Date: Jun 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Convalescent plasma ~500 mL ABO compatible convalescent apheresis plasma	Biological: 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.
No Intervention: Standard of care Treated as per institutional standard of care.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Were Intubated or Died [Day 30]

   Endpoint of the need for intubation or patient death

Secondary Outcome Measures

1. Time to Intubation or In-hospital Death [Day 30]

   Time in days from randomization to occurrence of intubation or death

2. Ventilator-free Days by Day 30 [Day 30]

   Number of days off ventilator at 30 days

3. Death by Day 30 [Day 30]

   Occurrence of patient death at 30 days

4. Length of Stay in Intensive Care Unit (ICU) [Day 30]

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

5. Need for Renal Replacement Therapy [Day 30]

   Need for new renal replacement therapy

6. Need for Extracorporeal Membrane Oxygenation (ECMO) [Day 30]

   Requirement for extracorporeal membrane oxygenation (ECMO)

7. Development of Myocarditis [Day 30]

   New diagnosis of myocarditis

8. In-hospital Death [Day 90]

   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.

9. Time to In-hospital Death [Day 90]

   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.

10. Length of Stay in Hospital [Day 90]

    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.

11. Number of Participants With Grade 3 and 4 Serious Adverse Events [Day 30]

    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)

12. Number of Participants With CCP Transfusion-associated Adverse Events (AE) [Day 30]

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

13. Number of Participants With Grade 3, 4, or 5 Serious Adverse Events [Day 30]

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

14. Patient Reported Outcome Using Change in EQ-5D-5L Score [Baseline and Day 30]

    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.

15. Patient Reported Outcome- Quality-adjusted Life Days [Day 30]

    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.

16. Cost of Intervention and Hospital Stay [Day 30]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ≥16 years old (>18 years of age in the United States)

• Admitted to hospital with confirmed COVID-19 respiratory illness

• Receiving supplemental oxygen

• 500 mL of ABO compatible convalescent plasma is available

Exclusion Criteria:

• Onset of respiratory symptoms >12 days prior to randomization

• Intubated or plan in place for intubation

• Plasma is contraindicated (e.g. history of anaphylaxis from transfusion)

• Decision in place for no active treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brooklyn Hospital	Brooklyn	New York	United States	11201
2	Lower Manhattan Hospital	New York	New York	United States	10038
3	Weill Cornell Medical Center	New York	New York	United States	10065
4	Hospital Universitário Antônio Pedro (HUAP)	Niterói		Brazil	24070-035
5	Hemario	Rio De Janeiro		Brazil	20211-030
6	Peter Lougheed Center	Calgary	Alberta	Canada	T1Y 6J4
7	Foothills Medical Centre	Calgary	Alberta	Canada	T2N 2T9
8	Rockyview General Hospital	Calgary	Alberta	Canada	T2V 1P9
9	University of Alberta - Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
10	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
11	Sturgeon Community Hospital	St. Albert	Alberta	Canada	T8N 6C4
12	Fraser Health Authority - Abbotsford Regional Hospital and Cancer Centre	Abbotsford	British Columbia	Canada	V2S 0C2
13	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
14	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
15	Royal Jubilee Hospital	Victoria	British Columbia	Canada	V8R 1J8
16	Victoria General Hospital	Victoria	British Columbia	Canada	V8Z 6R5
17	St. Boniface General Hospital	Winnipeg	Manitoba	Canada	R2H 2A6
18	Health Sciences Centre Winnipeg	Winnipeg	Manitoba	Canada	R3A 1R9
19	Grace General Hospital	Winnipeg	Manitoba	Canada	R3J 3M7
20	Vitalité Health Network - Acadie-Bathurst	Bathurst	New Brunswick	Canada	E2A 4L7
21	Vitalité Health Network - Restigouche	Campbellton	New Brunswick	Canada	E3N 3G2
22	Vitalité Health Network- Northwest	Edmundston	New Brunswick	Canada	E3V 4E4
23	Dr. Georges-L.-Dumont University Hospital Centre	Moncton	New Brunswick	Canada	E1C 2Z3
24	Lakeridge Health Ajax Pickering	Ajax	Ontario	Canada	L1S 2J4
25	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2
26	Juravinski Hospital	Hamilton	Ontario	Canada	L8V 1C3
27	St. Joseph's Healthcare	Hamilton	Ontario	Canada	M6R 1B5
28	Grand River Hospital	Kitchener	Ontario	Canada	N2G 1G3
29	St. Mary's Hospital	Kitchener	Ontario	Canada	N2M 1B2
30	London Health Sciences Centre - University Hospital	London	Ontario	Canada	N6A 5A5
31	Victoria Hospital	London	Ontario	Canada	N6A 5W9
32	Markham Stouffville Hospital	Markham	Ontario	Canada	L3P 7P3
33	Trillium Health Partners - Mississauga Hospital	Mississauga	Ontario	Canada	L5B 1B8
34	Trillium Health Partners - Credit Valley	Mississauga	Ontario	Canada	L5M 2N1
35	North York General Hospital	North York	Ontario	Canada	M2K 1E1
36	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
37	Ottawa Hospital - General Campus	Ottawa	Ontario	Canada	K1H 8L6
38	Ottawa Hospital - Civic Campus	Ottawa	Ontario	Canada	K1Y 4E9
39	Queensway Carleton Hospital	Ottawa	Ontario	Canada	K2H 8P4
40	Bluewater Health	Sarnia	Ontario	Canada	N7T 6S3
41	Scarborough Health Network, Centenary Hospital	Scarborough	Ontario	Canada	M1E 4B9
42	Scarborough Health Network, General Hospital	Scarborough	Ontario	Canada	M1P 2V5
43	Scarborough Health Network, Birchmount Hospital	Scarborough	Ontario	Canada	M1W 3W3
44	Niagara Health System - St. Catherines	St. Catherines	Ontario	Canada	L2S 0A9
45	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
46	Unity Health St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
47	Sinai Health System	Toronto	Ontario	Canada	M5G 1X5
48	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
49	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
50	Unity Health, St. Joseph's Health Care Centre	Toronto	Ontario	Canada	M6R 1B5
51	Windsor Regional Hospital - Metropolitan Campus	Windsor	Ontario	Canada	N8W 1L9
52	Windsor Regional Hospital - Ouellette Campus	Windsor	Ontario	Canada	N9A 1E1
53	L'Hopital Chicoutimi	Chicoutimi	Quebec	Canada	G7H 5H6
54	Hôpital de la Cité-de-la-Santé	Laval	Quebec	Canada	H7M 3L9
55	Hôpital Charles-Le Moyne	Longueuil	Quebec	Canada	J4V 2H1
56	Hotel Dieu Hospital of Lévis	Lévis	Quebec	Canada	G6V 3Z1
57	Hôpital Maisonneuve-Rosemont	Montréal	Quebec	Canada	H1T 2M4
58	Centre hospitalier de l'Université de Montréal	Montréal	Quebec	Canada	H2X 3E4
59	Montréal General Hospital	Montréal	Quebec	Canada	H3G 1A4
60	Centre hospitalier universitaire Sainte-Justine	Montréal	Quebec	Canada	H3T 1C5
61	Jewish General Hospital	Montréal	Quebec	Canada	H3T 1E2
62	McGill University Health Centre	Montréal	Quebec	Canada	H4A 3J1
63	Hôpital du Sacré-Coeur de Montreal	Montréal	Quebec	Canada	H4J 1C5
64	Centre Hospitalier Universitaire (CHU) de Québec - Université Laval	Quebec City	Quebec	Canada	G1R 2J6
65	Institut Universitaire de cardiologie et pneumologie de Québec	Quebec City	Quebec	Canada	G1V 4G5
66	Centre hospitalier régional de St-Jérôme	Saint-Jérôme	Quebec	Canada	J7Z 5T3
67	Centre Hospitalier Universitaire de Sherbrooke (CHUS) - Hôpital Hôtel-Dieu	Sherbrooke	Quebec	Canada	J1G 2E8
68	Centre Hospitalier Universitaire de Sherbrooke (CHUS) - Hôpital Fleurimont	Sherbrooke	Quebec	Canada	J1H 5H3
69	Centre hospitalier affilié universitaire régional de Trois-Rivières	Trois-Rivières	Quebec	Canada	G8Z 3R9
70	Regina General Hospital	Regina	Saskatchewan	Canada	S4P 0W5
71	Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 1A5
72	St. Paul's Hospital	Saskatoon	Saskatchewan	Canada	S7M 0Z9
73	Royal University Hospital	Saskatoon	Saskatchewan	Canada	S7N 0W8

Sponsors and Collaborators

• Hamilton Health Sciences Corporation
• Canadian Blood Services
• Héma-Québec
• University of Toronto
• Université de Montréal
• Weill Medical College of Cornell University
• New York Blood Center

Investigators

• Principal Investigator: Donald M Arnold, MD, McMaster University

Study Documents (Full-Text)

• Study Protocol - Jan 15, 2021
• Statistical Analysis Plan - Mar 19, 2021

More Information

Additional Information:

• Publication of trial results in Nature Medicine

Publications

• 2. FDA USFDA. Investigational COVID-19 Convalescent Plasma - Emergency INDs [Web]. 2020 [Available from: https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds accessed March 26th 2020.
• Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet. 2020 Feb 29;395(10225):689-697. doi: 10.1016/S0140-6736(20)30260-9. Epub 2020 Jan 31. Erratum in: Lancet. 2020 Feb 4;:.

• Responsible Party: Hamilton Health Sciences Corporation
• ClinicalTrials.gov Identifier: NCT04348656
• Other Study ID Numbers: CONCOR-1; NCT04418518
• First Posted: Apr 16, 2020
• Last Update Posted: Mar 3, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Hamilton Health Sciences Corporation: Convalescent plasma; Transfusion; SARS-CoV-2; Passive immunization
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Period Title: Overall Study
STARTED	627	313
Baseline Population	625	313
Intention to Treat Analysis	614	307
Per Protocol Analysis	548	303
COMPLETED	614	307
NOT COMPLETED	13	6

Baseline Characteristics

Arm/Group Title	Convalescent Plasma	Standard of Care	Total
Arm/Group Description	~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.	Treated as per institutional standard of care.	Total of all reporting groups
Overall Participants	625	313	938
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.7 (16.0)	67.1 (14.8)	67.5 (15.6)
Age, Customized (Count of Participants)
>= 60 years	438 70.1%	218 69.6%	656 69.9%
< 60 years	187 29.9%	95 30.4%	282 30.1%
Sex: Female, Male (Count of Participants)
Female	256 41%	128 40.9%	384 40.9%
Male	369 59%	185 59.1%	554 59.1%
Race/Ethnicity, Customized (Count of Participants)
White	305 48.8%	153 48.9%	458 48.8%
Asian	104 16.6%	46 14.7%	150 16%
Hispanic or Latino	34 5.4%	9 2.9%	43 4.6%
Black	25 4%	11 3.5%	36 3.8%
Other	38 6.1%	28 8.9%	66 7%
Unknown	119 19%	66 21.1%	185 19.7%
Region of Enrollment (Count of Participants)
Canada	529 84.6%	265 84.7%	794 84.6%
United States	89 14.2%	45 14.4%	134 14.3%
Brazil	7 1.1%	3 1%	10 1.1%
Pregnancy present at randomization (Count of Participants)
Count of Participants [Participants]	4 0.6%	1 0.3%	5 0.5%
ABO blood group (Count of Participants)
O	270 43.2%	113 36.1%	383 40.8%
A	235 37.6%	121 38.7%	356 38%
B	89 14.2%	57 18.2%	146 15.6%
AB	31 5%	22 7%	53 5.7%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.0 (7.5)	30.0 (7.4)	30.0 (7.4)
Body Mass Index (Count of Participants)
BMI < 30 kg/m^2	256 41%	123 39.3%	379 40.4%
BMI >= 30 kg/m^2	198 31.7%	102 32.6%	300 32%
BMI Unknown	171 27.4%	88 28.1%	259 27.6%
Presence of comorbidity (Count of Participants)
Diabetes	220 35.2%	108 34.5%	328 35%
Cardiac disease	385 61.6%	197 62.9%	582 62%
Baseline respiratory diseases	147 23.5%	79 25.2%	226 24.1%
Abnormal CT chest or chest x-ray result before randomization (Count of Participants)
Count of Participants [Participants]	563 90.1%	266 85%	829 88.4%
Medication for other research study at baseline (Count of Participants)
Count of Participants [Participants]	53 8.5%	41 13.1%	94 10%
Medication for COVID-19 at baseline (Count of Participants)
Azithromycin	279 44.6%	137 43.8%	416 44.3%
Other antibiotics	405 64.8%	186 59.4%	591 63%
Systemic corticosteroids	496 79.4%	258 82.4%	754 80.4%
Antiviral medications	165 26.4%	80 25.6%	245 26.1%
Anticoagulants	355 56.8%	180 57.5%	535 57%
Other COVID-19 medications	79 12.6%	39 12.5%	118 12.6%
Medication not for COVID-19 at baseline (Count of Participants)
Angiotensin-converting enzyme inhibitor	85 13.6%	63 20.1%	148 15.8%
Angiotensin-converting enzyme receptor blocker	77 12.3%	47 15%	124 13.2%
Non-steroidal anti-inflammatory drugs	77 12.3%	52 16.6%	129 13.8%
Colchicine	5 0.8%	2 0.6%	7 0.7%
Systemic corticosteroids	61 9.8%	35 11.2%	96 10.2%
Inhaled corticosteroids	84 13.4%	42 13.4%	126 13.4%
Immunomodulatory agents	22 3.5%	18 5.8%	40 4.3%
Anticoagulants	135 21.6%	64 20.4%	199 21.2%
Systemic corticosteroid at baseline (Count of Participants)
Count of Participants [Participants]	504 80.6%	262 83.7%	766 81.7%
Fraction of inhaled oxygen (FiO2) at the time of randomization (percentage of oxygen) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of oxygen]	49.5 (25.2)	48.8 (25.1)	49.3 (25.2)
Time from any symptom onset to randomization (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	8.0 (3.8)	7.8 (3.4)	7.9 (3.7)
Time from COVID-19 diagnosis to randomization (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	4.9 (3.6)	5.1 (4.4)	5.0 (3.9)
Location at time of randomization (Count of Participants)
Ward	505 80.8%	260 83.1%	765 81.6%
Intensive care unit	120 19.2%	53 16.9%	173 18.4%
Enrolled in other clinical trials (Count of Participants)
Count of Participants [Participants]	168 26.9%	98 31.3%	266 28.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Were Intubated or Died
Description	Endpoint of the need for intubation or patient death
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	199 31.8%	86 27.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	wald test
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Intubation or In-hospital Death
Description	Time in days from randomization to occurrence of intubation or death
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Mean (Standard Deviation) [days]	22.8 (11.0)	23.4 (11.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Ventilator-free Days by Day 30
Description	Number of days off ventilator at 30 days
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Mean (Standard Deviation) [days]	23.4 (10.4)	24.0 (10.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	t-test, 2 sided
	Comments	bootstrap estimates based on resampling process
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -2.1 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	bootstrap estimates based on resampling process

4. Secondary Outcome

Title	Death by Day 30
Description	Occurrence of patient death at 30 days
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	141 22.6%	63 20.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	wald test
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Length of Stay in Intensive Care Unit (ICU)
Description	Number of days spent in the intensive care unit (ICU) over the 30-day period following randomization
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Mean (Standard Deviation) [days]	4.3 (7.9)	3.7 (7.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Need for Renal Replacement Therapy
Description	Need for new renal replacement therapy
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	10 1.6%	6 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	t-test, 2 sided
	Comments	bootstrap estimates based on resampling process
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.31 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	bootstrap estimates based on resampling process

7. Secondary Outcome

Title	Need for Extracorporeal Membrane Oxygenation (ECMO)
Description	Requirement for extracorporeal membrane oxygenation (ECMO)
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	0 0%	1 0.3%

8. Secondary Outcome

Title	Development of Myocarditis
Description	New diagnosis of myocarditis
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	0 0%	0 0%

9. Secondary Outcome

Title	In-hospital Death
Description	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.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	625	313
Count of Participants [Participants]	156 25%	69 22%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	wald test
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Time to In-hospital Death
Description	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.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	625	313
Mean (Standard Deviation) [days]	16.3 (17.1)	14.8 (16.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments
	Method	Regression, Cox
	Comments	competing risk analysis
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	competing risk analysis

11. Secondary Outcome

Title	Length of Stay in Hospital
Description	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.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	625	313
Mean (Standard Deviation) [days]	16.3 (17.1)	14.8 (16.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants With Grade 3 and 4 Serious Adverse Events
Description	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)
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on the primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	92 14.7%	30 9.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	wald test
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95%; 1.04 to 2.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments	The cumulative incidence of Grade 3 and 4 serious AEs is described as a hazard ratio.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Regression, Cox
	Comments	competing risk analysis
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 95%; 1.08 to 2.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	competing risk analysis

13. Secondary Outcome

Title	Number of Participants With CCP Transfusion-associated Adverse Events (AE)
Description	Number of participants experiencing CCP transfusion-associated adverse events (AE), as defined by the International Society of Blood Tranfusion (ISBT ) classification
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	0
Count of Participants [Participants]	35 5.6%	0 0%

14. Secondary Outcome

Title	Number of Participants With Grade 3, 4, or 5 Serious Adverse Events
Description	Number of Participants with Grade 3-5 (CTCAE v4.0) serious adverse events reported to Day 30
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Intention to treat population with data on primary outcome available

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	614	307
Count of Participants [Participants]	205 32.8%	81 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	wald test
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 1.02 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Patient Reported Outcome Using Change in EQ-5D-5L Score
Description	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.
Time Frame	Baseline and Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	272	157
Mean (Standard Deviation) [units on a scale]	0.150 (0.2588)	0.157 (0.2859)

16. Secondary Outcome

Title	Patient Reported Outcome- Quality-adjusted Life Days
Description	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.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	341	194
Mean (Standard Deviation) [quality adjusted life days]	17.959 (9.0363)	18.037 (8.9771)

17. Secondary Outcome

Title	Cost of Intervention and Hospital Stay
Description	Cost per patient calculated using cost of the intervention and costs of the hospital stay
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Convalescent Plasma	Standard of Care
Arm/Group Description	~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.	Treated as per institutional standard of care.
Measure Participants	341	194
Mean (Standard Deviation) [Canadian dollars]	23516.74 (21373.80)	20025.05 (17957.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Standard of Care
	Comments
	Type of Statistical Test	Other
	Comments	Incremental cost per quality-adjusted life day gained (ICER)- this is a summary measure of the cost-effectiveness of the intervention, compared to the control group. This is calculated using the cost (derived from cost of the intervention and cost of hospital stay based on the payer's perspective) per patient and the quality-adjusted life days calculated using the EQ-5D-5L results.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ICER (CAD)
	Estimated Value	-44623.01
	Confidence Interval	(2-Sided) 95%; -525369.24 to 436123.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	ICER is reported in Canadian dollars. 95% CI is calculated by 1000 bootstrap sampling using bias-corrected accelerated method.

Adverse Events

Time Frame	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).
Adverse Event Reporting Description	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.
Arm/Group Title	Convalescent Plasma		Standard of Care
Arm/Group Description	~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.		Treated as per institutional standard of care.
All Cause Mortality
	Convalescent Plasma		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	160/625 (25.6%)		70/313 (22.4%)
Serious Adverse Events
	Convalescent Plasma		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	205/614 (33.4%)		81/307 (26.4%)
Blood and lymphatic system disorders
Anemia	2/614 (0.3%)		0/307 (0%)
Disseminated intravascular coagulation	1/614 (0.2%)		0/307 (0%)
Hemolytic uremic syndrome	0/614 (0%)		1/307 (0.3%)
Cardiac disorders
Cardiac arrest	3/614 (0.5%)		2/307 (0.7%)
Asystole	4/614 (0.7%)		0/307 (0%)
Atrial fibrillation	0/614 (0%)		2/307 (0.7%)
Cardiac disorders - Other	1/614 (0.2%)		0/307 (0%)
Heart failure	1/614 (0.2%)		0/307 (0%)
Ventricular tachycardia	0/614 (0%)		1/307 (0.3%)
Gastrointestinal disorders
Duodenal ulcer	1/614 (0.2%)		0/307 (0%)
Retroperitoneal hemorrhage	0/614 (0%)		1/307 (0.3%)
General disorders
Death NOS	14/614 (2.3%)		4/307 (1.3%)
Multi-organ failure	6/614 (1%)		3/307 (1%)
Fever	1/614 (0.2%)		0/307 (0%)
Hepatobiliary disorders
Cholecystitis	1/614 (0.2%)		0/307 (0%)
Hepatic pain	1/614 (0.2%)		0/307 (0%)
Infections and infestations
Sepsis	11/614 (1.8%)		5/307 (1.6%)
Lung infection	6/614 (1%)		4/307 (1.3%)
Infections and infestations - Other	3/614 (0.5%)		1/307 (0.3%)
Investigations
Cardiac troponin T increased	0/614 (0%)		1/307 (0.3%)
CPK increased	1/614 (0.2%)		0/307 (0%)
Neutrophil count decreased	0/614 (0%)		1/307 (0.3%)
Metabolism and nutrition disorders
Hypernatremia	1/614 (0.2%)		0/307 (0%)
Hypoalbuminemia	1/614 (0.2%)		0/307 (0%)
Hypocalcemia	1/614 (0.2%)		0/307 (0%)
Metabolism and nutrition disorders - Other	1/614 (0.2%)		0/307 (0%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/614 (0.2%)		0/307 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1/614 (0.2%)		0/307 (0%)
Nervous system disorders
Intracranial hemorrhage	4/614 (0.7%)		0/307 (0%)
Depressed level of consciousness	1/614 (0.2%)		1/307 (0.3%)
Stroke	0/614 (0%)		2/307 (0.7%)
Encephalopathy	1/614 (0.2%)		0/307 (0%)
Hydrocephalus	1/614 (0.2%)		0/307 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions - Other	1/614 (0.2%)		0/307 (0%)
Psychiatric disorders
Delirium	1/614 (0.2%)		1/307 (0.3%)
Renal and urinary disorders
Acute kidney injury	12/614 (2%)		7/307 (2.3%)
Renal and urinary disorders - Other	2/614 (0.3%)		0/307 (0%)
Urinary retention	0/614 (0%)		1/307 (0.3%)
Urine output decreased	1/614 (0.2%)		0/307 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	70/614 (11.4%)		33/307 (10.7%)
Hypoxia	57/614 (9.3%)		22/307 (7.2%)
Adult respiratory distress syndrome	10/614 (1.6%)		2/307 (0.7%)
Respiratory, thoracic and mediastinal disorders - Other	9/614 (1.5%)		3/307 (1%)
Dyspnea	6/614 (1%)		1/307 (0.3%)
Aspiration	4/614 (0.7%)		1/307 (0.3%)
Pneumonitis	3/614 (0.5%)		0/307 (0%)
Pulmonary edema	3/614 (0.5%)		0/307 (0%)
Transfusion associated circulatory overload	2/614 (0.3%)		0/307 (0%)
Pneumothorax	1/614 (0.2%)		1/307 (0.3%)
Pulmonary fibrosis	1/614 (0.2%)		1/307 (0.3%)
Transfusion associated dyspnea	1/614 (0.2%)		0/307 (0%)
Possible transfusion related acute lung injury	1/614 (0.2%)		0/307 (0%)
Pleural hemorrhage	1/614 (0.2%)		0/307 (0%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other	1/614 (0.2%)		0/307 (0%)
Surgical and medical procedures
Surgical and medical procedures - Other	1/614 (0.2%)		0/307 (0%)
Vascular disorders
Hypotension	8/614 (1.3%)		0/307 (0%)
Thromboembolic event	4/614 (0.7%)		3/307 (1%)
Other (Not Including Serious) Adverse Events
	Convalescent Plasma		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/614 (17.9%)		35/307 (11.4%)
Blood and lymphatic system disorders
Anemia	14/614 (2.3%)		3/307 (1%)
Infections and infestations
Infections and infestations, other	13/614 (2.1%)		7/307 (2.3%)
Urinary tract infection	7/614 (1.1%)		2/307 (0.7%)
Investigations
Lymphocyte count decreased	17/614 (2.8%)		8/307 (2.6%)
Metabolism and nutrition disorders
Hyperglycemia	13/614 (2.1%)		5/307 (1.6%)
Hypermagnesemia	9/614 (1.5%)		1/307 (0.3%)
Hypophosphatemia	8/614 (1.3%)		1/307 (0.3%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	18/614 (2.9%)		6/307 (2%)
Vascular disorders
Hypertension	11/614 (1.8%)		2/307 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.