CONvalescent Plasma for Hospitalized Adults With COVID-19... | NCT04348656

Name	Class
Canadian Blood Services	OTHER
Héma-Québec	OTHER
University of Toronto	OTHER
Université de Montréal

Description Module

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).

Label	Type	Description	Intervention Names
Convalescent plasma	Experimental	~500 mL ABO compatible convalescent apheresis plasma	Biological: Convalescent plasma
Standard of care	No Intervention	Treated as per institutional standard of care.

Name	Type	Description	Arm Group Labels	Other Names
Convalescent plasma	Biological	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.

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

Measure	Description	Time Frame
Time to Intubation or In-hospital Death	Time in days from randomization to occurrence of intubation or death	Day 30
Ventilator-free Days by Day 30	Number of days off ventilator at 30 days

Name	Affiliation	Role
Donald M Arnold, MD	McMaster University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Brooklyn Hospital		Brooklyn	New York	11201	United States
Lower Manhattan Hospital

PubMed Identifier	Type	Citation
32014114	Background	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.
	Background	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.
34504336

Label	URL
Publication of trial results in Nature Medicine	View source

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 15, 2021	Nov 4, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Were Intubated or Died

Endpoint of the need for intubation or patient death

Intention to treat population with data on primary outcome available

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants	OG000614 OG001307

Title

Denominators

Categories

Title	Measurements
	OG000199 OG00186

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		wald test		0.18		Risk Ratio (RR)	1.16			2-Sided	95	0.94	1.43					Superiority

Secondary

Time to Intubation or In-hospital Death

Time in days from randomization to occurrence of intubation or death

Intention to treat population with data on primary outcome available

Posted

Mean

Standard Deviation

days

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

Ventilator-free Days by Day 30

Number of days off ventilator at 30 days

Intention to treat population with data on primary outcome available

Posted

Mean

Standard Deviation

days

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

Death by Day 30

Occurrence of patient death at 30 days

Intention to treat population with data on primary outcome available

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

Length of Stay in Intensive Care Unit (ICU)

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

Intention to treat population with data on primary outcome available

Posted

Mean

Standard Deviation

days

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

Need for Renal Replacement Therapy

Need for new renal replacement therapy

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.

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Secondary

Need for Extracorporeal Membrane Oxygenation (ECMO)

Requirement for extracorporeal membrane oxygenation (ECMO)

Intention to treat population with data on primary outcome available

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

Development of Myocarditis

New diagnosis of myocarditis

Intention to treat population with data on primary outcome available

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

In-hospital Death

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.

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

Posted

Count of Participants

Participants

Day 90

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts

Secondary

Time to In-hospital Death

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.

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

Posted

Mean

Standard Deviation

days

Day 90

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts

Secondary

Length of Stay in Hospital

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.

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

Posted

Mean

Standard Deviation

days

Day 90

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts

Secondary

Number of Participants With Grade 3 and 4 Serious Adverse Events

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)

Intention to treat population with data on the primary outcome available

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts

Secondary

Number of Participants With CCP Transfusion-associated Adverse Events (AE)

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

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.

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Secondary

Number of Participants With Grade 3, 4, or 5 Serious Adverse Events

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

Intention to treat population with data on primary outcome available

Posted

Count of Participants

Participants

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Units	Counts
Participants

Secondary

Patient Reported Outcome Using Change in EQ-5D-5L Score

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.

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Day 30

ID	Title	Description
OG000	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.

Secondary

Patient Reported Outcome- Quality-adjusted Life Days

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.

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.

Posted

Mean

Standard Deviation

quality adjusted life days

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care

Secondary

Cost of Intervention and Hospital Stay

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

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.

Posted

Mean

Standard Deviation

Canadian dollars

Day 30

ID	Title	Description
OG000	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.
OG001	Standard of Care	Treated as per institutional standard of care.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG00070 affected614 at risk EG00133 affected307 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG00057 affected614 at risk EG00122 affected307 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (12.1)	Systematic Assessment		EG00012 affected614 at risk EG0017 affected307 at risk
Death NOS	General disorders	MedDRA (12.1)	Systematic Assessment		EG00014 affected614 at risk EG0014 affected307 at risk
Sepsis	Infections and infestations	MedDRA (12.1)	Systematic Assessment		EG00011 affected614 at risk EG0015 affected307 at risk
Adult respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG00010 affected614 at risk EG0012 affected307 at risk
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0009 affected614 at risk EG0013 affected307 at risk
Lung infection	Infections and infestations	MedDRA (12.1)	Systematic Assessment		EG0006 affected614 at risk EG0014 affected307 at risk
Multi-organ failure	General disorders	MedDRA (12.1)	Systematic Assessment		EG0006 affected614 at risk EG0013 affected307 at risk
Hypotension	Vascular disorders	MedDRA (12.1)	Systematic Assessment		EG0008 affected614 at risk EG0010 affected307 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0006 affected614 at risk EG0011 affected307 at risk
Thromboembolic event	Vascular disorders	MedDRA (12.1)	Systematic Assessment		EG0004 affected614 at risk EG0013 affected307 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0004 affected614 at risk EG0011 affected307 at risk
Cardiac arrest	Cardiac disorders	MedDRA (12.1)	Systematic Assessment		EG0003 affected614 at risk EG0012 affected307 at risk
Asystole	Cardiac disorders	MedDRA (12.1)	Systematic Assessment		EG0004 affected614 at risk EG0010 affected307 at risk
Infections and infestations - Other	Infections and infestations	MedDRA (12.1)	Systematic Assessment		EG0003 affected614 at risk EG0011 affected307 at risk
Intracranial hemorrhage	Nervous system disorders	MedDRA (12.1)	Systematic Assessment		EG0004 affected614 at risk EG0010 affected307 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0003 affected614 at risk EG0010 affected307 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0003 affected614 at risk EG0010 affected307 at risk
Transfusion associated circulatory overload	Respiratory, thoracic and mediastinal disorders	ISBT	Systematic Assessment	TACO is characterized by any four of the following: acute respiratory distress, tachycardia, increased blood pressure, acute or worsening pulmonary edema on chest xray, evidence of positive fluid balance within 6h of completion of transfusion	EG0002 affected614 at risk EG0010 affected307 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (12.1)	Systematic Assessment		EG0002 affected614 at risk EG0010 affected307 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0012 affected307 at risk
Delirium	Psychiatric disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0011 affected307 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0011 affected307 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0011 affected307 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0011 affected307 at risk
Renal and urinary disorders - Other	Renal and urinary disorders	MedDRA (12.1)	Systematic Assessment		EG0002 affected614 at risk EG0010 affected307 at risk
Stroke	Nervous system disorders	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0012 affected307 at risk
Transfusion associated dyspnea	Respiratory, thoracic and mediastinal disorders	ISBT	Systematic Assessment	Respiratory distress within 24h of transfusion that does meet criteria for TACO, TRALI, or allergic reaction. Respiratory distress should be the most prominent clinical feature and should not be explained by the pt's condition or another known cause	EG0001 affected614 at risk EG0010 affected307 at risk
Possible transfusion related acute lung injury	Respiratory, thoracic and mediastinal disorders	ISBT	Systematic Assessment	In patients with no acute lung injury prior to transfusion, a new acute lung injury meeting ISBT criteria that is present during or within 6 hours of transfusion.	EG0001 affected614 at risk EG0010 affected307 at risk
Cardiac disorders - Other	Cardiac disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Cardiac troponin T increased	Investigations	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0011 affected307 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
CPK increased	Investigations	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Encephalopathy	Nervous system disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Fever	General disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Heart failure	Cardiac disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Hemolytic uremic syndrome	Blood and lymphatic system disorders	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0011 affected307 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Hydrocephalus	Nervous system disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Hypernatremia	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Metabolism and nutrition disorders - Other	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Neutrophil count decreased	Investigations	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0011 affected307 at risk
Pregnancy, puerperium and perinatal conditions - Other	Pregnancy, puerperium and perinatal conditions	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Retroperitoneal hemorrhage	Gastrointestinal disorders	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0011 affected307 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Surgical and medical procedures - Other	Surgical and medical procedures	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Urinary retention	Renal and urinary disorders	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0011 affected307 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (12.1)	Systematic Assessment		EG0000 affected614 at risk EG0011 affected307 at risk
Pleural hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Urine output decreased	Renal and urinary disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA (12.1)	Systematic Assessment		EG0001 affected614 at risk EG0010 affected307 at risk

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Title	Description
BG000	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.
BG001	Standard of Care	Treated as per institutional standard of care.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	160	625	205	614	110	614
EG001	Standard of Care	Treated as per institutional standard of care.	70	313	81	307	35	307

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphocyte count decreased	Investigations	MedDRA (12.1)	Systematic Assessment	EG00017 affected614 at risk EG0018 affected307 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (12.1)	Systematic Assessment	EG00018 affected614 at risk EG0016 affected307 at risk
Infections and infestations, other	Infections and infestations	MedDRA (12.1)	Systematic Assessment	EG00013 affected614 at risk EG0017 affected307 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment	EG00013 affected614 at risk EG0015 affected307 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (12.1)	Systematic Assessment	EG00014 affected614 at risk EG0013 affected307 at risk
Hypertension	Vascular disorders	MedDRA (12.1)	Systematic Assessment	EG00011 affected614 at risk EG0012 affected307 at risk
Hypermagnesemia	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment	EG0009 affected614 at risk EG0011 affected307 at risk
Hypophosphatemia	Metabolism and nutrition disorders	MedDRA (12.1)	Systematic Assessment	EG0008 affected614 at risk EG0011 affected307 at risk
Urinary tract infection	Infections and infestations	MedDRA (12.1)	Systematic Assessment	EG0007 affected614 at risk EG0012 affected307 at risk