EMPACTA: A Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04372186
• Collaborator: (none)
• Enrollment: 377
• Locations: 51
• Arms: 2
• Anticipated Duration (Months): 18.6
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study (EMPACTA) will a) evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia, and b) include an optional long-term extension for eligible participants to explore the long-term sequelae of resolved COVID-19 pneumonia.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Pneumonia	Drug: Placebo; Drug: Tocilizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 377 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia
• Actual Study Start Date: May 14, 2020
• Actual Primary Completion Date: Aug 18, 2020
• Anticipated Study Completion Date: Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will receive one intravenous (IV) infusion of placebo, in addition to SOC. Up to one additional infusion may be given.	Drug: Placebo; Participants will receive one dose of IV placebo matched to TCZ. Up to one additional dose may be given.
Experimental: Tocilizumab Participants will receive one IV infusion of TCZ in addition to SOC. Up to one additional infusion may be given.	Drug: Tocilizumab; Participants will receive one IV infusion of TCZ 8 mg/kg, with a maximum dose of 800 mg. Up to one additional dose may be given.

Outcome Measures

Primary Outcome Measures

1. Cumulative Proportion of Participants Who Died or Required Mechanical Ventilation by Day 28 [Up to Day 28]

   Cumulative proportion is measured as a percentage of participants meeting the endpoint.

Secondary Outcome Measures

1. Time to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or >/= 2 Liters (L) Supplemental Oxygen) [Up to Day 28]

2. Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status [Up to Day 28]

   Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2 liters supplemental oxygen) - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen - ICU, requiring intubation and mechanical ventilation - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support - Death

3. Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (Whichever Occurred First) [Up to Day 28]

4. Mortality Rate by Day 28 [Up to Day 28]

5. Clinical Status on 7-Category Ordinal Scale at Day 28 [Day 28]

   Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2 liters supplemental oxygen) - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen - ICU, requiring intubation and mechanical ventilation - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support - Death

6. Percentage of Participants With Adverse Events [Up to Day 60]

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Hospitalized

• COVID-19 pneumonia confirmed by a positive polymerase chain reaction (PCR) of any specimen and radiographic imaging

• SpO2 < 94% while on ambient air

Inclusion Criteria Specific to Long-Term Extension

• Participated in Study ML42528 (EMPACTA) (includes participants who completed or discontinued early from the main study)

Exclusion Criteria

• Known severe allergic reactions to TCZ or other monoclonal antibodies

• Require continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or invasive mechanical ventilation

• Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)

• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments

• Immunocompromised (besides well-controlled HIV) or on immunosuppressive therapy (except for steroids for COVID), advanced cancer

• Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months

• Participating in another interleukin (IL)-6 antagonist clinical trial or other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor)

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 10 x upper limit of normal (ULN) detected within 24 hours at screening (according to local laboratory reference ranges)

• Absolute neutrophil count (ANC) < 1000/uL at screening (according to local laboratory reference ranges)

• Platelet count < 50,000/uL at screening (according to local laboratory reference ranges)

• Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination

• Treatment with an investigational drug within 5 half lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medical Monitor)

• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

• Any history of Diverticulitis or GI perforation

• Use of systemic corticosteroids unless on a stable chronic dose

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner - University Medical Center Phoenix; In-Patient Pharmacy	Phoenix	Arizona	United States	85006
2	Univ of AZ Coll of Med	Tucson	Arizona	United States	85724
3	El Centro Regional Medical Center	El Centro	California	United States	92243
4	eStudySite	La Mesa	California	United States	91942
5	Highland Hospital Oakland	Oakland	California	United States	94602
6	St. Joseph'S Hospital	Orange	California	United States	92563
7	San Leandro Hospital; Inpatient Pharmacy	San Leandro	California	United States	94578
8	Larkin Community Hospital Palm Springs Campus (Hialeah)	Hialeah	Florida	United States	33012
9	Miami Veterans Administration Healthcare System - NAVREF	Miami	Florida	United States	33125
10	University of Miami Pulmonary	Miami	Florida	United States	33125
11	Larkin Community Hospital	South Miami	Florida	United States	33143
12	St. Lukes Boise Medical Center	Boise	Idaho	United States	83712
13	Ochsner Clinic	New Orleans	Louisiana	United States	70121
14	Holy Cross Germantown Hospital	Germantown	Maryland	United States	20876
15	Holy Cross Hospital	Silver Spring	Maryland	United States	20910
16	Henry Ford Health System	Detroit	Michigan	United States	48202
17	St. Joseph'S Regional Medical Center	Paterson	New Jersey	United States	07503
18	San Juan Oncology Associates	Farmington	New Mexico	United States	87401
19	St. Barnabas Hospital	Bronx	New York	United States	10457
20	SUNY Downstate Medical Center.	Brooklyn	New York	United States	11203
21	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
22	Flushing Hospital	Flushing	New York	United States	11355
23	Jamaica Hospital Medical Center	Jamaica	New York	United States	11418
24	Harlem Hospital	New York	New York	United States	10037
25	Canton-Potsdam Hospital	Potsdam	New York	United States	13676
26	Novant Health Presbyterian Medical Center (Presbyterian Hospital)	Charlotte	North Carolina	United States	28204
27	Cape Fear Valley Medical Center	Fayetteville	North Carolina	United States	28304
28	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
29	Valley Baptist Medical Center	Harlingen	Texas	United States	78550
30	Michael E Debakey VA Medical Center	Houston	Texas	United States	77030
31	McAllen Medical Center	McAllen	Texas	United States	78503
32	Sentara Medical Group	Virginia Beach	Virginia	United States	23462
33	Hospital E Maternidade Celso Pierro PUCCAMP	Campinas	SP	Brazil	13060-904
34	Centro Multidisciplinar de Estudos Clínicos CEMEC FMABC	Sao Bernardo Do Campo	SP	Brazil	09715-090
35	BR Trials - Pesquisa Clínica	Sao Paulo	SP	Brazil	03325-050
36	Aga Khan University Hospital	Nairobi		Kenya	00100
37	Organismo Publico Descentralizado Hospital Juarez de Mexico	Ciudad De México		Mexico	07760
38	Hospital General de Culiacan	Culiacan		Mexico	80230
39	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico		Mexico
40	Hospital Militar Central	Jesus Maria		Peru	Lima 11
41	Hospital Nacional Sergio E. Bernales	Lima		Peru	15003
42	Hospital Nacional Arzobispo Loayza; Oncology	Lima		Peru	1
43	Hospital Nacional Cayetano Heredia	Lima		Peru	31
44	Hospital Nacional Hipolito; Unanue	Lima		Peru	Lima 10
45	Hospital Maria Auxiliadora	Lima		Peru	Lima 29
46	Hospital Nacional Dos de Mayo	Lima		Peru
47	University of the Free State	Bloemfontein		South Africa	9301
48	George Provincial Hospital	George		South Africa	6259
49	Peermed Clinical Trial Centre	Kempton Park		South Africa	1619
50	Mzansi Ethical Research Centre	Middelburg		South Africa	1055
51	Milpark Hospital	Parktown West		South Africa	2196

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Aug 15, 2020
• Statistical Analysis Plan - Aug 31, 2020

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT04372186
• Other Study ID Numbers: ML42528
• First Posted: May 1, 2020
• Last Update Posted: Sep 27, 2021
• Last Verified: Sep 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; Pneumonia

Study Results

Participant Flow

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Period Title: Overall Study
STARTED	249	128
COMPLETED	225	115
NOT COMPLETED	24	13

Baseline Characteristics

Arm/Group Title	Tocilizumab	Placebo	Total
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.	Total of all reporting groups
Overall Participants	249	128	377
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.0 (14.3)	55.6 (14.9)	55.9 (14.4)
Sex: Female, Male (Count of Participants)
Female	99 39.8%	55 43%	154 40.8%
Male	150 60.2%	73 57%	223 59.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	143 57.4%	68 53.1%	211 56%
Not Hispanic or Latino	106 42.6%	60 46.9%	166 44%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	52 20.9%	25 19.5%	77 20.4%
Asian	5 2%	1 0.8%	6 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.8%	1 0.3%
Black or African American	35 14.1%	22 17.2%	57 15.1%
White	134 53.8%	65 50.8%	199 52.8%
More than one race	4 1.6%	2 1.6%	6 1.6%
Unknown or Not Reported	19 7.6%	12 9.4%	31 8.2%

Outcome Measures

1. Primary Outcome

Title	Cumulative Proportion of Participants Who Died or Required Mechanical Ventilation by Day 28
Description	Cumulative proportion is measured as a percentage of participants meeting the endpoint.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

mITT population = all randomized participants who received study treatment, grouped according to the treatment assigned at randomization.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	249	128
Number (95% Confidence Interval) [Percentage of Participants]	12.04 4.8%	19.26 15%

2. Secondary Outcome

Title	Time to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or >/= 2 Liters (L) Supplemental Oxygen)
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

mITT population = all randomized participants who received study treatment, grouped according to the treatment assigned at randomization. Participants not receiving study treatment were excluded from analyses.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	249	128
Median (95% Confidence Interval) [Days]	6.0	7.5

3. Secondary Outcome

Title	Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
Description	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2 liters supplemental oxygen) - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen - ICU, requiring intubation and mechanical ventilation - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support - Death
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

mITT population = all randomized participants who received study treatment, grouped according to the treatment assigned at randomization.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	249	128
Median (95% Confidence Interval) [Days]	6.0	7.0

4. Secondary Outcome

Title	Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (Whichever Occurred First)
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

mITT population = all randomized participants who received study treatment, grouped according to the treatment assigned at randomization.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	249	128
Median (95% Confidence Interval) [Days]	NA	NA

5. Secondary Outcome

Title	Mortality Rate by Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	249	128
Number (95% Confidence Interval) [Percentage of Participants]	10.4 4.2%	8.6 6.7%

6. Secondary Outcome

Title	Clinical Status on 7-Category Ordinal Scale at Day 28
Description	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2 liters supplemental oxygen) - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen - ICU, requiring intubation and mechanical ventilation - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support - Death
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

mITT population = all randomized participants who received study treatment, grouped according to the treatment assigned at randomization.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	249	128
1	85.9 34.5%	82.8 64.7%
2	0.4 0.2%	1.6 1.3%
3	2.0 0.8%	0.8 0.6%
4	0.4 0.2%	0.8 0.6%
5	0.8 0.3%	3.9 3%
6	0 0%	1.6 1.3%
7	10.4 4.2%	8.6 6.7%

7. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description

Safety evaluable population = all participants who received any amount of study drug, grouped according to the treatment first received rather than by the treatment assigned at randomization.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.	Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
Measure Participants	250	127
Number [Percentage of participants]	50.8 20.4%	52.8 41.3%

Adverse Events

Time Frame	Up to Day 60
Adverse Event Reporting Description	The safety evaluable population included all participants who received any amount of study drug, grouped according to the treatment first received rather than by the treatment assigned at randomization.
Arm/Group Title	Tocilizumab		Placebo
Arm/Group Description	Participants received one IV infusion of TCZ in addition to SOC with up to one additional infusion.		Participants received one intravenous (IV) infusion of placebo, in addition to SOC, with up to one additional infusion.
All Cause Mortality
	Tocilizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/250 (11.6%)		15/127 (11.8%)
Serious Adverse Events
	Tocilizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/250 (15.2%)		25/127 (19.7%)
Blood and lymphatic system disorders
Anaemia of chronic disease	0/250 (0%)	0	1/127 (0.8%)	1
Blood loss anaemia	0/250 (0%)	0	1/127 (0.8%)	1
Disseminated intravascular coagulation	1/250 (0.4%)	1	0/127 (0%)	0
Thrombocytopenia	1/250 (0.4%)	1	0/127 (0%)	0
Cardiac disorders
Acute coronary syndrome	1/250 (0.4%)	1	0/127 (0%)	0
Acute myocardial infarction	1/250 (0.4%)	1	0/127 (0%)	0
Atrial fibrillation	1/250 (0.4%)	1	1/127 (0.8%)	1
Cardiac arrest	2/250 (0.8%)	2	1/127 (0.8%)	1
Cardiac failure	1/250 (0.4%)	1	1/127 (0.8%)	1
Cardio-respiratory arrest	2/250 (0.8%)	2	0/127 (0%)	0
Myocardial infarction	0/250 (0%)	0	1/127 (0.8%)	1
Gastrointestinal disorders
Gastric ulcer	1/250 (0.4%)	1	0/127 (0%)	0
Gastric varices	1/250 (0.4%)	1	0/127 (0%)	0
Intestinal perforation	1/250 (0.4%)	1	0/127 (0%)	0
Mesenteric haematoma	0/250 (0%)	0	1/127 (0.8%)	1
Upper gastrointestinal haemorrhage	0/250 (0%)	0	1/127 (0.8%)	1
General disorders
Multiple organ dysfunction syndrome	1/250 (0.4%)	1	0/127 (0%)	0
Hepatobiliary disorders
Gallbladder rupture	1/250 (0.4%)	1	0/127 (0%)	0
Hepatic failure	1/250 (0.4%)	1	0/127 (0%)	0
Infections and infestations
Bacteraemia	1/250 (0.4%)	1	0/127 (0%)	0
COVID-19	1/250 (0.4%)	1	0/127 (0%)	0
COVID-19 pneumonia	2/250 (0.8%)	2	3/127 (2.4%)	3
Cellulitis	1/250 (0.4%)	1	0/127 (0%)	0
Cellulitis of male external genital organ	1/250 (0.4%)	1	0/127 (0%)	0
Cholecystitis infective	1/250 (0.4%)	1	0/127 (0%)	0
Device related infection	1/250 (0.4%)	1	0/127 (0%)	0
Pneumonia	0/250 (0%)	0	3/127 (2.4%)	3
Pneumonia bacterial	0/250 (0%)	0	2/127 (1.6%)	2
Pneumonia pseudomonal	1/250 (0.4%)	1	0/127 (0%)	0
Pneumonia staphylococcal	1/250 (0.4%)	1	0/127 (0%)	0
Sepsis	1/250 (0.4%)	1	0/127 (0%)	0
Septic shock	5/250 (2%)	5	3/127 (2.4%)	3
Investigations
Transaminases increased	2/250 (0.8%)	2	0/127 (0%)	0
Metabolism and nutrition disorders
Acidosis	0/250 (0%)	0	1/127 (0.8%)	1
Fluid overload	0/250 (0%)	0	1/127 (0.8%)	1
Hypovolaemia	0/250 (0%)	0	1/127 (0.8%)	1
Metabolic acidosis	0/250 (0%)	0	1/127 (0.8%)	1
Nervous system disorders
Brain injury	1/250 (0.4%)	1	0/127 (0%)	0
Brain stem stroke	1/250 (0.4%)	1	0/127 (0%)	0
Cerebral infarction	1/250 (0.4%)	1	0/127 (0%)	0
Cerebrovascular accident	2/250 (0.8%)	2	1/127 (0.8%)	1
Embolic stroke	0/250 (0%)	0	1/127 (0.8%)	1
Ischaemic cerebral infarction	0/250 (0%)	0	1/127 (0.8%)	1
Renal and urinary disorders
Acute kidney injury	1/250 (0.4%)	1	3/127 (2.4%)	3
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/250 (0.4%)	1	0/127 (0%)	0
Acute respiratory distress syndrome	5/250 (2%)	5	1/127 (0.8%)	1
Acute respiratory failure	4/250 (1.6%)	4	3/127 (2.4%)	3
Pulmonary embolism	3/250 (1.2%)	3	1/127 (0.8%)	1
Respiratory acidosis	0/250 (0%)	0	1/127 (0.8%)	1
Respiratory distress	0/250 (0%)	0	1/127 (0.8%)	1
Respiratory failure	4/250 (1.6%)	4	2/127 (1.6%)	2
Skin and subcutaneous tissue disorders
Stasis dermatitis	1/250 (0.4%)	1	0/127 (0%)	0
Vascular disorders
Deep vein thrombosis	1/250 (0.4%)	1	0/127 (0%)	0
Hypotension	0/250 (0%)	0	1/127 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Tocilizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/250 (11.2%)		8/127 (6.3%)
Gastrointestinal disorders
Constipation	16/250 (6.4%)	16	4/127 (3.1%)	4
Psychiatric disorders
Anxiety	15/250 (6%)	15	4/127 (3.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.