Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC)

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT04546581
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), National Institutes of Health (NIH) (NIH), International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) (Other)
• Enrollment: 593
• Locations: 39
• Arms: 2
• Actual Duration (Months): 7.4
• Patients Per Site: 15.2
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

This protocol will serve as a platform for assessing treatments for adult patients hospitalized for medical management of COVID-19 without related serious end-organ failure. Trials will involve sites around the world strategically chosen to ensure rapid enrollment. This trial will compare hyperimmune intravenous immunoglobulin (hIVIG) with matched placebo, when added to standard of care (SOC), for preventing further disease progression and mortality related to COVID-19. SOC will include remdesivir unless it is contraindicated for an individual patient.

Condition or Disease	Intervention/Treatment	Phase
COVID; COVID-19; SARS-CoV-2; SARS (Severe Acute Respiratory Syndrome)	Biological: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG); Other: Placebo; Drug: Remdesivir	Phase 3

Detailed Description

The primary endpoint of this trial in hospitalized patients is an ordinal outcome based on the patient's clinical status on Day 7. It includes 7 mutually exclusive categories capturing the range of organ dysfunction that may be associated with progression of COVID-19, such as respiratory dysfunction and coagulation-related complications. The ordinal endpoint is defined as follows:

1. Death

2. End-organ failure

3. Life-threatening end-organ dysfunction

4. Serious end-organ dysfunction

5. Moderate end-organ dysfunction

6. Limiting symptoms due to COVID-19

7. No limiting symptoms due to COVID-19

Secondary endpoints include time to the 3 least favorable categories, time to the 2 most favorable categories, and the pulmonary only and thrombotic only components of the primary ordinal outcome. Mortality, adverse events (AEs), including infusion reactions, and biological correlates of therapeutic activity are also assessed. Because there is no established endpoint for evaluating the clinical efficacy of treatments for COVID-19, other clinically relevant outcomes, including outcomes used in other COVID-19 treatment trials, will be recorded. Thus, the randomized groups (hIVIG + SOC versus placebo + SOC ) can be compared for multiple outcomes, and results can be compared or combined with other trials.

Participants will be randomized (1:1) to a single infusion of hIVIG + SOC or placebo + SOC on the day of randomization (Day 0). Participants taking remdesivir prior to randomization may be enrolled if eligibility criteria are met. Randomized participants who were not taking remdesivir before randomization will start taking remdesivir immediately following the infusion of hIVIG or placebo unless remdesivir is contraindicated. Participants will be followed for 28 days and, if the trial goes to completion, the primary analysis will be completed after all participants are followed for 28 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 593 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19
• Actual Study Start Date: Oct 8, 2020
• Actual Primary Completion Date: May 21, 2021
• Actual Study Completion Date: May 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Group Participants in this group will receive the investigational product and standard of care (SOC).	Biological: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG); Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion.; Drug: Remdesivir; Remdesivir will be given to participants in both groups as standard of care (SOC).
Placebo Comparator: Control Group Participants in this group will receive a placebo and standard of care (SOC).	Other: Placebo; Participants will receive a single infusion of the placebo (saline).; Drug: Remdesivir; Remdesivir will be given to participants in both groups as standard of care (SOC).

Outcome Measures

Primary Outcome Measures

1. Ordinal Outcome Scale - Day 7 [7 days]

   The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19 Outcome is reported as the percent of participants in each of 7 categories. Primary ordinal outcome based on the patient's clinical status on Day 7. It includes 7 mutually exclusive categories capturing the range of organ dysfunction that may be associated with progression of COVID-19, such as respiratory dysfunction and coagulation-related complications. Minimum value = 1, Maximum value = 7 Higher scores mean a worse outcome

2. Primary Safety Outcome - Death, SAE or Grade 3 or 4 Events Through Day 7 [Through Day 7]

   Number of participants with death, SAE or Grade 3 or 4 event through Day 7

Secondary Outcome Measures

1. N Reaching 3 Least Favorable Categories [All of follow-up (through Day 28)]

   N Reaching 3 least favorable categories of ordinal outcome (Categories 5, 6, 7: life-threatening end organ dysfunction, end organ failure, or death)

2. N Reaching 2 Most Favorable Categories [All of follow-up (through Day 28)]

   N Reaching 2 most favorable categories of ordinal outcome (Categories 1 and 2: not requiring oxygen with or without limiting symptoms due to COVID-19)

3. N Discharged or in Most Favorable Category [All of follow-up (through Day 28)]

   N discharged from hospital or reaching most favorable ordinal category (category 1: not requiring oxygen and no limiting symptoms due to COVID-19)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• SARS-CoV-2 infection documented by polymerase chain reaction (PCR) or other nucleic acid test (NAT) within 3 days prior to randomization OR documented by NAT more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection

• Symptomatic COVID-19 disease

• Duration of symptoms attributable to COVID-19 ≤ 12 days

• Requiring inpatient hospital medical care for clinical manifestations of COVID-19 (admission for public health or quarantine only is not included)

• Willingness to abstain from participation in other COVID-19 treatment trials until after study Day 7

• Provision of informed consent by participant or legally authorized representative

Exclusion Criteria:

• Prior receipt of SARS-CoV-2 hIVIG or convalescent plasma from a person who recovered from COVID-19 at any time

• Prior receipt of standard IVIG (not hyperimmune to SARS-CoV-2) within 45 days

• Current or predicted imminent (within 24 hours) requirement for any of the following:

1. Invasive ventilation

2. Non-invasive ventilation

3. Extracorporeal membrane oxygenation

4. Mechanical circulatory support

5. Continuous vasopressor therapy

• History of allergy to IVIG or plasma products

• History of selective IgA deficiency with documented presence of anti-IgA antibodies

• Any medical conditions for which receipt of the required volume of intravenous fluid may be dangerous to the patient (includes New York Association Class III or IV stage heart failure)

• Any of the following thrombotic or procoagulant disorders:

1. Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomization

2. History of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome

• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penrose Hospital	Colorado Springs	Colorado	United States	80907
2	St. Francis Health Services	Colorado Springs	Colorado	United States	80907
3	St. Anthony Hospital	Lakewood	Colorado	United States	80228
4	Saint Anthony North Health Campus	Westminster	Colorado	United States	80023
5	Washington VA Medical Center	Washington	District of Columbia	United States	20422
6	Redmond Regional Medical Center	Rome	Georgia	United States	30165
7	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892
8	University of Massachusetts	Worcester	Massachusetts	United States	01665
9	Hennepin Healthcare Research Institute/HCMC	Minneapolis	Minnesota	United States	55415
10	University of Missouri	Columbia	Missouri	United States	65212
11	Cox Medical Centers	Springfield	Missouri	United States	65807
12	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina	United States	28394
13	Ohio Health Research Institute	Columbus	Ohio	United States	43215
14	Hendrick Medical Center	Abilene	Texas	United States	79601
15	CHRISTUS Spohn Shoreline Hospital	Corpus Christi	Texas	United States	78404
16	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235
17	CJW Chippenham Medical Center	Richmond	Virginia	United States	23225
18	Henrico Doctors' Hospital (HCA)	Richmond	Virginia	United States	23229
19	Aarhus Universitetshospital, Skejby	Aarhus		Denmark
20	Bispebjerg Hospital	Copenhagen		Denmark
21	CHIP, Department of Infectious Diseases, Section 2100	Copenhagen		Denmark
22	Herlev-Gentofte Hospital	Hellerup		Denmark
23	Nordsjællands Hospital, Hillerød	Hillerød		Denmark	3400
24	Hvidovre University Hospital, Department of Infectious Diseases	Hvidovre		Denmark
25	Kolding Sygehus	Kolding		Denmark
26	Odense University Hospital	Odense		Denmark
27	Democritus University of Thrace	Alexandroupoli	Thrace	Greece	68131
28	3rd Dept of Medicine, Medical School, NKUA	Athens		Greece	11527
29	1st Respiratory Medicine Dept, Athens University Medical School	Athens		Greece
30	Attikon University General Hospital	Athens		Greece
31	Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital	Athens		Greece
32	NCGM	Tokyo		Japan
33	Fujita Health University Hospital	Toyoake		Japan
34	Institute of Human Virology-Nigeria (IHVN)	Abuja		Nigeria
35	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
36	Hospital Universitari Vall d'Hebron	Barcelona	Catalonia	Spain	08035
37	Hospital del Mar	Barcelona		Spain	08002
38	Hospital Clínic de Barcelona	Barcelona		Spain	08036
39	Royal Free Hospital	London		United Kingdom

Sponsors and Collaborators

• University of Minnesota
• National Institute of Allergy and Infectious Diseases (NIAID)
• National Institutes of Health (NIH)
• International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

Investigators

• Principal Investigator: James Neaton, PhD, University of Minnesota
• Study Chair: Mark Polizzotto, MD, The Kirby Institute, University of New South Wales

Study Documents (Full-Text)

• Study Protocol - Aug 20, 2020
• Statistical Analysis Plan - Mar 27, 2021
• Informed Consent Form - Sep 14, 2020

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04546581
• Other Study ID Numbers: INSIGHT 013
• First Posted: Sep 14, 2020
• Last Update Posted: Apr 4, 2022
• Last Verified: Mar 1, 2022

• 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
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: COVID-19; Severe Acute Respiratory Syndrome; Remdesivir; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies

Study Results

Participant Flow

Arm/Group Title	Intervention Group	Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
Period Title: Overall Study
STARTED	301	292
COMPLETED	288	279
NOT COMPLETED	13	13

Baseline Characteristics

Arm/Group Title	Intervention Group	Control Group	Total
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Total of all reporting groups
Overall Participants	301	292	593
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58.4	59.7	59.0
Sex: Female, Male (Count of Participants)
Female	149 49.5%	108 37%	257 43.3%
Male	152 50.5%	184 63%	336 56.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	1 0.3%	2 0.3%
Asian	39 13%	31 10.6%	70 11.8%
Native Hawaiian or Other Pacific Islander	2 0.7%	1 0.3%	3 0.5%
Black or African American	40 13.3%	47 16.1%	87 14.7%
White	174 57.8%	160 54.8%	334 56.3%
More than one race	9 3%	13 4.5%	22 3.7%
Unknown or Not Reported	36 12%	39 13.4%	75 12.6%

Outcome Measures

1. Primary Outcome

Title	Ordinal Outcome Scale - Day 7
Description	The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19 Outcome is reported as the percent of participants in each of 7 categories. Primary ordinal outcome based on the patient's clinical status on Day 7. It includes 7 mutually exclusive categories capturing the range of organ dysfunction that may be associated with progression of COVID-19, such as respiratory dysfunction and coagulation-related complications. Minimum value = 1, Maximum value = 7 Higher scores mean a worse outcome
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Group	Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
Measure Participants	295	284
Category 7 - Died	5 1.7%	5 1.7%
Category 6 - End organ failure	9 3%	13 4.5%
Category 5 - Life threatening end organ dysfunction	26 8.6%	26 8.9%
Category 4 - Serious end organ dysfunction	25 8.3%	30 10.3%
Category 3 - Moderate end organ dysfunction	32 10.6%	28 9.6%
Category 2 - Limiting symptoms due to COVID-19	67 22.3%	61 20.9%
Category 1 - No limiting symptoms due to COVID-19	129 42.9%	116 39.7%
Missing	2 0.7%	5 1.7%

2. Primary Outcome

Title	Primary Safety Outcome - Death, SAE or Grade 3 or 4 Events Through Day 7
Description	Number of participants with death, SAE or Grade 3 or 4 event through Day 7
Time Frame	Through Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Group	Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
Measure Participants	295	284
Count of Participants [Participants]	71 23.6%	70 24%

3. Secondary Outcome

Title	N Reaching 3 Least Favorable Categories
Description	N Reaching 3 least favorable categories of ordinal outcome (Categories 5, 6, 7: life-threatening end organ dysfunction, end organ failure, or death)
Time Frame	All of follow-up (through Day 28)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Group	Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
Measure Participants	295	284
Count of Participants [Participants]	45 15%	48 16.4%

4. Secondary Outcome

Title	N Reaching 2 Most Favorable Categories
Description	N Reaching 2 most favorable categories of ordinal outcome (Categories 1 and 2: not requiring oxygen with or without limiting symptoms due to COVID-19)
Time Frame	All of follow-up (through Day 28)

Outcome Measure Data

Analysis Population Description

Those in Category 2 at baseline are excluded from this analysis

Arm/Group Title	Intervention Group	Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
Measure Participants	219	206
Count of Participants [Participants]	178 59.1%	160 54.8%

5. Secondary Outcome

Title	N Discharged or in Most Favorable Category
Description	N discharged from hospital or reaching most favorable ordinal category (category 1: not requiring oxygen and no limiting symptoms due to COVID-19)
Time Frame	All of follow-up (through Day 28)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Group	Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).	Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
Measure Participants	295	284
Count of Participants [Participants]	268 89%	252 86.3%

Adverse Events

Time Frame	28 days
Arm/Group Title	Intervention Group		Control Group
Arm/Group Description	Participants in this group will receive the investigational product and standard of care (SOC). Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG): Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion. Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).		Participants in this group will receive a placebo and standard of care (SOC). Placebo: Participants will receive a single infusion of the placebo (saline). Remdesivir: Remdesivir will be given to participants in both groups as standard of care (SOC).
All Cause Mortality
	Intervention Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/301 (6%)		22/292 (7.5%)
Serious Adverse Events
	Intervention Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/301 (6%)		20/292 (6.8%)
Blood and lymphatic system disorders
Anaemia	1/301 (0.3%)	1	2/292 (0.7%)	2
Acute myeloid leukaemia	1/301 (0.3%)	1	0/292 (0%)	0
Blood loss anaemia	1/301 (0.3%)	1	0/292 (0%)	0
Hypertension	1/301 (0.3%)	1	0/292 (0%)	0
Pancytopenia	1/301 (0.3%)	1	0/292 (0%)	0
Cardiac disorders
Atrial fibrillation	1/301 (0.3%)	1	1/292 (0.3%)	1
Acute left ventricular failure	1/301 (0.3%)	1	0/292 (0%)	0
Myocardial infarction	1/301 (0.3%)	1	0/292 (0%)	0
Pulseless electrical activity	0/301 (0%)	0	1/292 (0.3%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/301 (0.3%)	1	0/292 (0%)	0
Intra-abdominal haemorrhage	1/301 (0.3%)	1	0/292 (0%)	0
General disorders
Headache	0/301 (0%)	0	1/292 (0.3%)	1
Pyrexia	0/301 (0%)	0	1/292 (0.3%)	1
Hepatobiliary disorders
Cholangitis	0/301 (0%)	0	1/292 (0.3%)	1
Infections and infestations
Sepsis	0/301 (0%)	0	1/292 (0.3%)	2
COVID-19	0/301 (0%)	0	1/292 (0.3%)	1
Escherichia bacteraemia	0/301 (0%)	0	1/292 (0.3%)	1
Septic shock	0/301 (0%)	0	1/292 (0.3%)	1
Psychiatric disorders
Psychotic disorder	0/301 (0%)	0	1/292 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/301 (1%)	3	1/292 (0.3%)	1
COVID-19 Pneumonia	1/301 (0.3%)	1	2/292 (0.7%)	2
Hypoxia	1/301 (0.3%)	1	2/292 (0.7%)	2
Dyspnoea	1/301 (0.3%)	1	1/292 (0.3%)	1
Acute respiratory failure	1/301 (0.3%)	1	0/292 (0%)	0
Pneumothorax	0/301 (0%)	0	1/292 (0.3%)	1
Pulmonary embolism	0/301 (0%)	0	1/292 (0.3%)	1
Respiratory failure	1/301 (0.3%)	1	0/292 (0%)	0
Other (Not Including Serious) Adverse Events
	Intervention Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/301 (26.2%)		53/292 (18.2%)
Blood and lymphatic system disorders
Anaemia	3/301 (1%)	3	0/292 (0%)	0
Haemoptysis	1/301 (0.3%)	1	0/292 (0%)	0
Haemorrhage	1/301 (0.3%)	1	0/292 (0%)	0
Leukopenia	1/301 (0.3%)	1	0/292 (0%)	0
Cardiac disorders
Hypotension	3/301 (1%)	3	1/292 (0.3%)	1
Atrial fibrillation	1/301 (0.3%)	1	1/292 (0.3%)	1
Hypertension	1/301 (0.3%)	1	1/292 (0.3%)	1
Tachycardia	0/301 (0%)	0	2/292 (0.7%)	2
Bradycardia	0/301 (0%)	0	1/292 (0.3%)	1
Left ventricular failure	1/301 (0.3%)	1	0/292 (0%)	0
Myocardial infarction	1/301 (0.3%)	1	0/292 (0%)	0
Myocarditis	0/301 (0%)	0	1/292 (0.3%)	1
Supraventricular tachycardia	0/301 (0%)	0	1/292 (0.3%)	1
Ear and labyrinth disorders
Oropharyngeal pain	0/301 (0%)	0	1/292 (0.3%)	1
Endocrine disorders
Blood glucose increased	0/301 (0%)	0	1/292 (0.3%)	1
Eye disorders
Vision blurred	1/301 (0.3%)	1	0/292 (0%)	0
Gastrointestinal disorders
Constipation	0/301 (0%)	0	1/292 (0.3%)	1
Diarrhoea	1/301 (0.3%)	1	0/292 (0%)	0
Nausea	0/301 (0%)	0	1/292 (0.3%)	1
General disorders
Pyrexia	10/301 (3.3%)	10	5/292 (1.7%)	6
Chills	10/301 (3.3%)	10	0/292 (0%)	0
Fatigue	1/301 (0.3%)	1	3/292 (1%)	3
Ageusia	1/301 (0.3%)	1	2/292 (0.7%)	2
Anosmia	1/301 (0.3%)	1	2/292 (0.7%)	2
Decreased appetite	1/301 (0.3%)	1	1/292 (0.3%)	1
Asthenia	1/301 (0.3%)	1	0/292 (0%)	0
Headache	0/301 (0%)	0	1/292 (0.3%)	1
Lethargy	1/301 (0.3%)	1	0/292 (0%)	0
Malaise	0/301 (0%)	0	1/292 (0.3%)	1
Hepatobiliary disorders
Alanine aminotransferase increased	1/301 (0.3%)	1	0/292 (0%)	0
Infections and infestations
Septic shock	1/301 (0.3%)	1	0/292 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/301 (0%)	0	1/292 (0.3%)	1
Chest pain	1/301 (0.3%)	1	0/292 (0%)	0
Muscle rigidity	1/301 (0.3%)	1	0/292 (0%)	0
Musculoskeletal chest pain	0/301 (0%)	0	1/292 (0.3%)	1
Non-cardiac chest pain	0/301 (0%)	0	1/292 (0.3%)	1
Psychiatric disorders
Anxiety	1/301 (0.3%)	1	1/292 (0.3%)	1
Mental status changes	0/301 (0%)	0	1/292 (0.3%)	1
Renal and urinary disorders
Acute kidney injury	1/301 (0.3%)	1	1/292 (0.3%)	1
Anuria	1/301 (0.3%)	1	0/292 (0%)	0
Oliguria	1/301 (0.3%)	1	0/292 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	10/301 (3.3%)	13	5/292 (1.7%)	6
Respiratory Distress	6/301 (2%)	7	5/292 (1.7%)	6
Respiratory Failure	4/301 (1.3%)	4	3/292 (1%)	3
Cough	2/301 (0.7%)	2	2/292 (0.7%)	2
Hypoxia	3/301 (1%)	3	0/292 (0%)	0
COVID-19 pneumonia	1/301 (0.3%)	1	1/292 (0.3%)	1
Acute respiratory failure	0/301 (0%)	0	1/292 (0.3%)	1
Bronchiectasis	1/301 (0.3%)	1	0/292 (0%)	0
Dependence on oxygen therapy	1/301 (0.3%)	1	0/292 (0%)	0
Dyspnoea, exertional	0/301 (0%)	0	1/292 (0.3%)	1
Interstitial lung disease	1/301 (0.3%)	1	0/292 (0%)	0
Pneumonia	1/301 (0.3%)	1	0/292 (0%)	0
Pneumothorax	0/301 (0%)	0	1/292 (0.3%)	1
Pulmonary edema	0/301 (0%)	0	1/292 (0.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.