C3PO: Convalescent Plasma in Outpatients With COVID-19

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04355767
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network (Other), University of Pittsburgh (Other), Medical University of South Carolina (Other)
• Enrollment: 511
• Locations: 53
• Arms: 2
• Actual Duration (Months): 7.6
• Patients Per Site: 9.6
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The overarching goal of this project is to confirm or refute the role of passive immunization as a safe and efficacious therapy in preventing the progression from mild to severe/critical COVID-19 illness and to understand the immunologic kinetics of anti-SARS-CoV-2 antibodies after passive immunization.The primary objective is to determine the efficacy and safety of a single dose of convalescent plasma (CP) for preventing the progression from mild to severe COVID-19 illness. The secondary objective is to characterize the immunologic response to CP administration.

This study will enroll adults presenting to the emergency department (ED) with mild, symptomatic, laboratory-confirmed COVID-19 illness, who are at high risk for progression to severe/critical illness, but who are clinically stable for outpatient management at randomization.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Biological: Convalescent Plasma; Biological: Saline	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 511 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical-trial of COVID-19 Convalescent Plasma in Outpatients
• Actual Study Start Date: Aug 11, 2020
• Actual Primary Completion Date: Mar 29, 2021
• Actual Study Completion Date: Mar 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Convalescent Plasma Participants receive 1 unit of convalescent plasma.	Biological: Convalescent Plasma; SARS-CoV-2 convalescent plasma with neutralizing SARS-CoV2 antibodies titers of ≥1:160 administered via intravenous (IV) infusion.
Placebo Comparator: Placebo Participants receive 1 unit of saline with multivitamin.	Biological: Saline; Saline with multivitamin administered via intravenous (IV) infusion..

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Disease Progression (Intention-to-treat Population) [15 days]

   Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

2. Number of Patients With Disease Progression (Per-protocol Population) [15 days]

   Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

Secondary Outcome Measures

1. Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization [30 days]

   This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity. 1 = Not hospitalized without limitation in activity (no symptoms) 2 = Not hospitalized with limitation in activity (continued symptoms) 3 = Hospitalized not on supplemental oxygen 4 = Hospitalized on supplemental oxygen by mask or nasal prongs 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula 6 = Hospitalized, intubated and mechanically ventilated 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy) 8 = Death

2. Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression [15 days]

   Assessed on the COVID Outpatient Ordinal Outcome Scale censored at 15 days after randomization. Scale provides more granular detail for outpatients than the WHO scale (adapted from Harrell and Lindsell, 2020). Worsening of symptoms is defined as any subject admitted to the hospital (level 1), seen in the emergency room (level 2), a patient who reports increased symptoms of 2 levels on the scale over a 24 hour period, or a patient who reports increased symptoms of 1 level observed for a 48 hour period. COVID Outpatient Ordinal Outcomes Scale 1 = patient requires care in the hospital 2 = patient requires care in the emergency department or urgent care 3 = patient at home with symptoms rated as moderate (defined as fever, shortness of breath, abdominal pain) 4 = patient at home with symptoms rated as mild (defined as afebrile, constitutional symptoms (flu-like illness) without shortness 5 = patient in their usual state of health

3. Number of Hospital-free Days During the 30 Days Following Randomization [30 days]

4. All-cause Mortality [Assessed at 30 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• One or more symptoms of COVID-19 illness and laboratory-confirmed SARS-CoV-2 infection

• Has at least one study defined risk factor for severe COVID-19 illness

• Clinical team deems stable for outpatient management without supplemental oxygen

• CP available at the site at the time of enrollment

• Duration of symptoms ≤ 7 days at ED presentation

• Informed consent from subject

Exclusion Criteria:

• Age less than 18 years

• Prisoner or ward of the state

• Presumed unable to complete follow-up assessments

• Prior adverse reaction(s) from blood product transfusion

• Receipt of any blood product within the past 120 days

• Treating clinical team unwilling to administer 300 ml fluid

• Enrollment in another interventional trial for COVID-19 illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chandler Regional Medical Center	Chandler	Arizona	United States	85224
2	Valleywise Health Medical Center	Phoenix	Arizona	United States	85008
3	UCSD Health La Jolla	La Jolla	California	United States	92037
4	Loma Linda University Medical Center	Loma Linda	California	United States	92354
5	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
6	Cedars-Sinai Medical Center	Los Angeles	California	United States	90211
7	UC Davis Medical Center	Sacramento	California	United States	95817
8	Stanford University	Stanford	California	United States	94305
9	Harbor-UCLA Medical Center	Torrance	California	United States	90502
10	University of Colorado Hospital	Aurora	Colorado	United States	80045
11	UF Health Shands Hospital	Gainesville	Florida	United States	32608
12	Jackson Memorial Hospital	Miami	Florida	United States	33136
13	Grady Memorial Hospital	Atlanta	Georgia	United States	30303
14	Rush University Medical Center	Chicago	Illinois	United States	60612
15	University of Illinois Hospital	Chicago	Illinois	United States	60612
16	University of Chicago Medical Center	Chicago	Illinois	United States	60637
17	University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
18	University of Louisville Hospital	Louisville	Kentucky	United States	40202
19	Maine Medical Center	Portland	Maine	United States	04102
20	Tufts Medical Center	Boston	Massachusetts	United States	02111
21	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
22	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
23	Baystate Medical Center	Springfield	Massachusetts	United States	01199
24	University of Michigan University Hospital	Ann Arbor	Michigan	United States	48109
25	Detroit Receiving Hospital	Detroit	Michigan	United States	48201
26	Harper University Hospital	Detroit	Michigan	United States	48201
27	Henry Ford Hospital	Detroit	Michigan	United States	48202
28	Sinai-Grace Hospital	Detroit	Michigan	United States	48235
29	Spectrum Health Hospitals Butterworth Hospital	Grand Rapids	Michigan	United States	49503
30	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
31	William Beaumont Hospital-Troy	Troy	Michigan	United States	48085
32	HealthPartners Methodist Hospital	Saint Louis Park	Minnesota	United States	55426
33	Regions Hospital	Saint Paul	Minnesota	United States	55101
34	Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
35	Cooper University Hospital	Camden	New Jersey	United States	08103
36	Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08901
37	University of New Mexico Hospital	Albuquerque	New Mexico	United States	87106
38	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203
39	Duke University Hospital	Durham	North Carolina	United States	27710
40	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27103
41	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
42	OSU Wexner Medical Center	Columbus	Ohio	United States	43210
43	Mercy St. Vincent Medical Center	Toledo	Ohio	United States	43608
44	Oregon Health & Science University Hospital	Portland	Oregon	United States	97239
45	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
46	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
47	Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141
48	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
49	William P. Clements Jr. University Hospital	Dallas	Texas	United States	75235
50	Ben Taub General Hospital	Houston	Texas	United States	77030
51	Memorial Hermann Texas Medical Center	Houston	Texas	United States	77030
52	University of Utah Healthcare	Salt Lake City	Utah	United States	84132
53	Froedtert Hospital	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Stanford University
• National Heart, Lung, and Blood Institute (NHLBI)
• Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network
• University of Pittsburgh
• Medical University of South Carolina

Investigators

• Principal Investigator: Clifton W Callaway, MD, PhD, University of Pittsburgh
• Principal Investigator: Valerie Durkalski-Mauldin, PhD, Medical University of South Carolina
• Principal Investigator: Frederick Korley, MD, PhD, University of Michigan
• Principal Investigator: Sharon Yeatts, PhD, Medical University of South Carolina
• Principal Investigator: Robert Silbergleit, MD, University of Michigan
• Principal Investigator: William Barsan, MD, University of Michigan
• Study Director: Kevin Schulman, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2021
• Informed Consent Form - Nov 4, 2020

More Information

Additional Information:

• SIREN Network
• Statistical Design and Analysis Plan for Sequential Parallel-Group RCT for COVID-19 (Harrell and Lindsell, 2020)

Publications

None provided.

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT04355767
• Other Study ID Numbers: C3PO; 1OT2HL156812-01
• First Posted: Apr 21, 2020
• Last Update Posted: Oct 19, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Recruitment Details	Patients were enrolled at 48 hospital emergency departments in 21 states.

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Period Title: Overall Study
STARTED	257	254
Intention-to-treat Population	257	254
Had Data for 15-day Outcome	257	254
COMPLETED	250	251
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Convalescent Plasma	Placebo	Total
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.	Total of all reporting groups
Overall Participants	257	254	511
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	54	54	54
Sex: Female, Male (Count of Participants)
Female	135 52.5%	139 54.7%	274 53.6%
Male	122 47.5%	115 45.3%	237 46.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	83 32.3%	73 28.7%	156 30.5%
Not Hispanic or Latino	170 66.1%	179 70.5%	349 68.3%
Unknown or Not Reported	4 1.6%	2 0.8%	6 1.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	8 3.1%	10 3.9%	18 3.5%
Black	49 19.1%	54 21.3%	103 20.2%
Other	28 10.9%	25 9.8%	53 10.4%
White	172 66.9%	165 65%	337 65.9%
Region of Enrollment (Count of Participants)
United States	257 100%	254 100%	511 100%
Eligibility risk factor (Count of Participants)
Age .50 yr	155 60.3%	155 61%	310 60.7%
Body-mass index ≥30	152 59.1%	150 59.1%	302 59.1%
Hypertension	105 40.9%	111 43.7%	216 42.3%
Current or former tobacco use	81 31.5%	71 28%	152 29.7%
Diabetes mellitus	76 29.6%	66 26%	142 27.8%
COPD or asthma	56 21.8%	68 26.8%	124 24.3%
Coronary artery disease	28 10.9%	23 9.1%	51 10%
Immunosuppression	33 12.8%	17 6.7%	50 9.8%
Chronic lung disease	16 6.2%	15 5.9%	31 6.1%
Chronic kidney disease	16 6.2%	12 4.7%	28 5.5%
Congestive heart disease	9 3.5%	11 4.3%	20 3.9%
Currently pregnant	3 1.2%	3 1.2%	6 1.2%
Organ transplant recipient	5 1.9%	0 0%	5 1%
Active cancer	2 0.8%	2 0.8%	4 0.8%
Sickle-cell disease	1 0.4%	0 0%	1 0.2%
Number of eligibility risk factors (Count of Participants)
1	51 19.8%	66 26%	117 22.9%
3	65 25.3%	65 25.6%	130 25.4%
≥3	141 54.9%	123 48.4%	264 51.7%
Other coexisting illness (Count of Participants)
Current or former alcohol abuse	20 7.8%	16 6.3%	36 7%
Current or former drug abuse	18 7%	17 6.7%	35 6.8%
Thromboembolic disorder	15 5.8%	10 3.9%	25 4.9%
Liver disease	12 4.7%	6 2.4%	18 3.5%
Other hematologic disorder	9 3.5%	8 3.1%	17 3.3%
Symptom duration before randomization (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	4	3	4
Interval between randomization and infusion (minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [minutes]	92	69	81

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Disease Progression (Intention-to-treat Population)
Description	Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Intention-to-treat population included all randomized participants.

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Measure Participants	257	254
Patients with a disease-progression event	77 30%	81 31.9%
Hospital admission for any reason	51 19.8%	56 22%
Seeking emergency or urgent care	25 9.7%	25 9.8%
Death without hospitalization	1 0.4%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Placebo
	Comments	Analysis is of patients with a disease-progression event. The trial required a sample size of 900 patients to detect an absolute between-group difference of 10 percentage points (the minimum difference that we considered to be clinically important) with a power of 85%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		A Bayesian framework was used to calculate a risk difference of 1.9 percentage points (placebo group minus convalescent-plasma group) with a 95% credible interval of -6.0 to 9.8. The posterior probability of superiority was calculated to be 0.68. Efficacy was defined as a posterior probability of 0.975 or more that the proportion of patients with outcome events was higher in the placebo group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Placebo
	Comments	Analysis is of patients with a disease-progression event.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -5.9 to 10.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference after adjustment for age, sex, symptom duration.

2. Primary Outcome

Title	Number of Patients With Disease Progression (Per-protocol Population)
Description	Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Per-protocol population included all the patients who had undergone randomization after the exclusion of those who did not receive the assigned trial product, had an identified eligibility violation, or had a disease-progression event before the initiation of treatment.

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Measure Participants	246	251
Patients with a disease-progression event	71 27.6%	80 31.5%
Hospital admission for any reason	47 18.3%	55 21.7%
Seeking emergency or urgent care	24 9.3%	25 9.8%
Death without hospitalization	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Placebo
	Comments	Analysis is of patients with a disease-progression event.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		A Bayesian framework was used to calculate a risk difference of 3.0 percentage points (placebo group minus convalescent-plasma group) with a 95% credible interval of -4.9 to 10.8. The posterior probability of superiority was calculated to be 0.76. Efficacy was defined as a posterior probability of 0.975 or more that the proportion of patients with outcome events was higher in the placebo group.

3. Secondary Outcome

Title	Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization
Description	This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity. 1 = Not hospitalized without limitation in activity (no symptoms) 2 = Not hospitalized with limitation in activity (continued symptoms) 3 = Hospitalized not on supplemental oxygen 4 = Hospitalized on supplemental oxygen by mask or nasal prongs 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula 6 = Hospitalized, intubated and mechanically ventilated 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy) 8 = Death
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Participants with available data are included in the analysis.

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Measure Participants	250	248
Severity rating 1	55 21.4%	55 21.7%
Severity rating 2	141 54.9%	133 52.4%
Severity rating 3	12 4.7%	17 6.7%
Severity rating 4	28 10.9%	35 13.8%
Severity rating 5	6 2.3%	5 2%
Severity rating 6	1 0.4%	0 0%
Severity rating 7	2 0.8%	2 0.8%
Severity rating 8	5 1.9%	1 0.4%

4. Secondary Outcome

Title	Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression
Description	Assessed on the COVID Outpatient Ordinal Outcome Scale censored at 15 days after randomization. Scale provides more granular detail for outpatients than the WHO scale (adapted from Harrell and Lindsell, 2020). Worsening of symptoms is defined as any subject admitted to the hospital (level 1), seen in the emergency room (level 2), a patient who reports increased symptoms of 2 levels on the scale over a 24 hour period, or a patient who reports increased symptoms of 1 level observed for a 48 hour period. COVID Outpatient Ordinal Outcomes Scale 1 = patient requires care in the hospital 2 = patient requires care in the emergency department or urgent care 3 = patient at home with symptoms rated as moderate (defined as fever, shortness of breath, abdominal pain) 4 = patient at home with symptoms rated as mild (defined as afebrile, constitutional symptoms (flu-like illness) without shortness 5 = patient in their usual state of health
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Intention-to-treat population

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Measure Participants	257	254
Count of Participants [Participants]	107 41.6%	116 45.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Hospital-free Days During the 30 Days Following Randomization
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Intention-to-treat population

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Measure Participants	257	254
Mean (Standard Deviation) [days]	28.3 (4.9)	28.6 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Convalescent Plasma, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	All-cause Mortality
Time Frame	Assessed at 30 days

Outcome Measure Data

Analysis Population Description

Intention-to-treat population

Arm/Group Title	Convalescent Plasma	Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.	Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
Measure Participants	257	254
Count of Participants [Participants]	5 1.9%	1 0.4%

Adverse Events

Time Frame	30 days
Arm/Group Title	Convalescent Plasma		Placebo
Arm/Group Description	Participants receive 1 unit of convalescent plasma (with neutralizing SARS-CoV2 antibodies) administered via intravenous (IV) infusion.		Participants receive 1 unit of saline with multivitamin administered via intravenous (IV) infusion.
All Cause Mortality
	Convalescent Plasma		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/257 (1.9%)		1/254 (0.4%)
Serious Adverse Events
	Convalescent Plasma		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/257 (23%)		64/254 (25.2%)
Blood and lymphatic system disorders
Anaemia	0/257 (0%)		1/254 (0.4%)
Cardiac disorders
Atrial fibrillation	1/257 (0.4%)		0/254 (0%)
Tachycardia	0/257 (0%)		1/254 (0.4%)
Gastrointestinal disorders
Abdominal pain	1/257 (0.4%)		1/254 (0.4%)
Vomiting	2/257 (0.8%)		0/254 (0%)
General disorders
Fatigue	1/257 (0.4%)		0/254 (0%)
Influenza like illness	0/257 (0%)		1/254 (0.4%)
Immune system disorders
Anaphylactic reaction	1/257 (0.4%)		0/254 (0%)
Infections and infestations
Pneumonia	30/257 (11.7%)		39/254 (15.4%)
Septic shock	0/257 (0%)		1/254 (0.4%)
Tooth abscess	1/257 (0.4%)		0/254 (0%)
Viral diarrhoea	1/257 (0.4%)		0/254 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	4/257 (1.6%)		0/254 (0%)
Investigations
Oesophagoscopy	0/257 (0%)		1/254 (0.4%)
Metabolism and nutrition disorders
Dehydration	2/257 (0.8%)		1/254 (0.4%)
Hyperglycemia	1/257 (0.4%)		0/254 (0%)
Hyperkalaemia	0/257 (0%)		1/254 (0.4%)
Hyponatraemia	0/257 (0%)		1/254 (0.4%)
Nervous system disorders
Epilepsy	1/257 (0.4%)		0/254 (0%)
Psychiatric disorders
Anxiety	1/257 (0.4%)		0/254 (0%)
Psychotic disorder	0/257 (0%)		1/254 (0.4%)
Renal and urinary disorders
Acute kidney injury	1/257 (0.4%)		0/254 (0%)
End stage renal disease, could not get outpatient dialysis	0/257 (0%)		1/254 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	3/257 (1.2%)		2/254 (0.8%)
Chronic obstructive pulmonary disease	0/257 (0%)		1/254 (0.4%)
Dyspnea	1/257 (0.4%)		8/254 (3.1%)
Epistaxis	1/257 (0.4%)		0/254 (0%)
Haemoptysis	0/257 (0%)		1/254 (0.4%)
Hypoxia	6/257 (2.3%)		5/254 (2%)
Pulmonary embolism	3/257 (1.2%)		2/254 (0.8%)
Vascular disorders
Hypotension	1/257 (0.4%)		0/254 (0%)
Iliac artery occlusion	0/257 (0%)		1/254 (0.4%)
Thrombophlebitis superficial	0/257 (0%)		1/254 (0.4%)
Other (Not Including Serious) Adverse Events
	Convalescent Plasma		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/257 (19.8%)		35/254 (13.8%)
Ear and labyrinth disorders
Vertigo	1/257 (0.4%)		0/254 (0%)
Gastrointestinal disorders
Abdominal pain	1/257 (0.4%)		2/254 (0.8%)
Dysphagia	1/257 (0.4%)		0/254 (0%)
Vomiting	1/257 (0.4%)		3/254 (1.2%)
General disorders
Chest pain	3/257 (1.2%)		7/254 (2.8%)
Fatigue	2/257 (0.8%)		0/254 (0%)
Infusion site extravasation	1/257 (0.4%)		0/254 (0%)
Pyrexia	1/257 (0.4%)		0/254 (0%)
Infections and infestations
Nasopharyngitis	1/257 (0.4%)		1/254 (0.4%)
Pneumonia	7/257 (2.7%)		1/254 (0.4%)
Sinusitis	1/257 (0.4%)		0/254 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/257 (0.4%)		0/254 (0%)
Fall	1/257 (0.4%)		0/254 (0%)
Infusion related reaction	11/257 (4.3%)		1/254 (0.4%)
Road traffic accident	1/257 (0.4%)		0/254 (0%)
Investigations
Coronavirus test positive	1/257 (0.4%)		2/254 (0.8%)
Metabolism and nutrition disorders
Decreased appetite	0/257 (0%)		1/254 (0.4%)
Dehydration	0/257 (0%)		2/254 (0.8%)
Hyperglycemia	0/257 (0%)		1/254 (0.4%)
Musculoskeletal and connective tissue disorders
Flank pain	2/257 (0.8%)		0/254 (0%)
Nervous system disorders
Dizziness	2/257 (0.8%)		1/254 (0.4%)
Migraine	3/257 (1.2%)		1/254 (0.4%)
Presyncope	0/257 (0%)		1/254 (0.4%)
Psychiatric disorders
Depression	1/257 (0.4%)		0/254 (0%)
Paranoia	0/257 (0%)		1/254 (0.4%)
Renal and urinary disorders
Nephrolithiasis	1/257 (0.4%)		0/254 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/257 (0.4%)		0/254 (0%)
Bronchospasm	1/257 (0.4%)		0/254 (0%)
Chronic obstructive pulmonary disease	1/257 (0.4%)		0/254 (0%)
Cough	0/257 (0%)		3/254 (1.2%)
Dyspnea	5/257 (1.9%)		9/254 (3.5%)
Hypoxia	0/257 (0%)		3/254 (1.2%)
Skin and subcutaneous tissue disorders
Ecchymosis	1/257 (0.4%)		0/254 (0%)
Rash	1/257 (0.4%)		0/254 (0%)
Surgical and medical procedures
Tooth extraction	1/257 (0.4%)		0/254 (0%)
Vascular disorders
Venous thrombosis limb	0/257 (0%)		1/254 (0.4%)

Limitations/Caveats

This study did not meet its maximum sample size of 900 participants due to a planned interim analysis that indicated that it was unlikely that there would be a difference in the rate of disease progression between the two groups if continued to the planned sample size.

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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.