RUXCOVID: Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04362137
• Collaborator: Incyte Corporation (Industry)
• Enrollment: 432
• Locations: 61
• Arms: 2
• Actual Duration (Months): 5.5
• Patients Per Site: 7.1
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This was a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 disease.

Condition or Disease	Intervention/Treatment	Phase
Cytokine Storm (Covid-19)	Drug: Ruxolitinib; Drug: Placebo	Phase 3

Detailed Description

This was a Phase III, multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of ruxolitinib in patients aged ≥12 years with COVID-19 disease. The study enrolled patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria were randomized in a 2:1 ratio to either oral ruxolitinib 5 mg twice daily + SoC or oral matching-image placebo + SoC for a total of 14 days. An additional 14 days of study drug could be given if in the opinion of the investigator the patient's clinical signs and symptoms did not improve, or worsen, and the potential benefit outweighed the potential risk.

The study included:

• Screening period of 0-2 days.

• Study period of 29 days (treatment of 14 days with possible extension of treatment to 28 days).

The primary objective was to evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29.

Study Design

• Study Type: Interventional
• Actual Enrollment: 432 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)
• Actual Study Start Date: May 2, 2020
• Actual Primary Completion Date: Oct 17, 2020
• Actual Study Completion Date: Oct 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ruxolitinib 5 mg Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Drug: Ruxolitinib; Ruxolitinib 5 mg tablets; Other Names: INC424
Placebo Comparator: Placebo Matching-image placebo for 14 days with possible extension of treatment to 28 days	Drug: Placebo; Matching-image placebo

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care [Day 1 - Day 29]

   Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis.

Secondary Outcome Measures

1. Clinical Status [Baseline, Day 15, Day 29]

   Clinical status is measured with the 9-point ordinal scale. The scoring is: Uninfected patients have a score 0 (no clinical or virological evidence of infection). Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as peripheral oxygen saturation (SpO2) ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). Patients who die have a score 8.

2. Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status [Baseline, Day 15, Day 29]

   Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.

3. Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status [Baseline, Day 15, Day 29]

   Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.

4. Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status [Baseline, Day 15, Day 29]

   Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.

5. Time to Improvement in Clinical Status [29 days]

   Time to improvement in clinical status from baseline category to one less severe category of the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Median time to improvement is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who did not achieve improvement and did not die are censored at their last clinical status assessment date.

6. Mean Change From Baseline in the Clinical Status [Baseline, Day 15, Day 29]

   Mean change from baseline in the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. A negative change from baseline in the clinical status is a favorable outcome.

7. Mortality Rate [Day 15, Day 29]

   Mortality rate is determined as the proportion of participants who died by study Day 15 and Day 29

8. Proportion of Patients Requiring Mechanical Ventilation [Day 1 - Day 29]

   Proportion of patients requiring mechanical ventilation. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who required mechanical ventilation at randomization are excluded from the analysis.

9. Duration of Hospitalization [29 days]

   Duration of hospitalization is defined as time to hospital discharge. Median time to hospital discharge is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who were not discharged and did not die are censored at their last assessment date.

10. Time to Hospital Discharge or to a NEWS2 Score of ≤2 [29 days]

    The time to hospital discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). Median time is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study.

11. Change From Baseline in NEWS2 Score [Baseline, Days 3, 5, 8, 11, 15, and 29]

    The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). At each visit, only patients with a value at both baseline and the respective visit are included. A negative change from baseline in NEWS2 score is a favorable outcome.

12. Change From Baseline in SpO2/FiO2 Ratio [Baseline, Day 15, Day 29]

    Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio). At each visit, only patients with a value at both baseline and the respective visit are included. A positive change from baseline in SpO2/FiO2 ratio is a favorable outcome.

13. Proportion of Patients With no Oxygen Therapy [Day 15, Day 29]

    Proportion of patients with no oxygen therapy (defined as oxygen saturation ≥ 94% on room air) at Days 15 and 29. Analyses are cumulative, thus analysis on each day includes all events till that day. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed.

Male and female patients aged ≥ 12 years (or ≥ the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals).

Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization.

Patients currently hospitalized or will be hospitalized prior to randomization.

Patients, who meet at least one of the below criteria:

• Pulmonary infiltrates (chest X ray or chest CT scan);

• Respiratory frequency ≥ 30/min;

• Requiring supplemental oxygen;

• Oxygen saturation ≤ 94% on room air;

• Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m).

Exclusion Criteria:

History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.

Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 μmol/L), or have estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation.

Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).

Currently intubated or intubated between screening and randomization. In intensive care unit (ICU) at time of randomization. Intubated or in ICU for COVID-19 disease prior to screening. Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra).

Unable to ingest tablets at randomization. Pregnant or nursing (lactating) women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Fullerton	California	United States	92835
2	Novartis Investigative Site	Aurora	Colorado	United States	80045
3	Novartis Investigative Site	Denver	Colorado	United States	80205
4	Novartis Investigative Site	Atlanta	Georgia	United States	30312
5	Novartis Investigative Site	Idaho Falls	Idaho	United States	83404
6	Novartis Investigative Site	Ann Arbor	Michigan	United States	48109
7	Novartis Investigative Site	Newark	New Jersey	United States	07103
8	Novartis Investigative Site	Bronx	New York	United States	10461
9	Novartis Investigative Site	Mesquite	Texas	United States	75149
10	Novartis Investigative Site	Seattle	Washington	United States	98104
11	Novartis Investigative Site	Madison	Wisconsin	United States	53705-3611
12	Novartis Investigative Site	C A B A	Buenos Aires	Argentina	CP1405
13	Novartis Investigative Site	Buenos Aires		Argentina	C1426AAM
14	Novartis Investigative Site	Buenos Aires		Argentina	C1430BKC
15	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	22640-000
16	Novartis Investigative Site	Blumenau	Santa Catarina	Brazil	89030101
17	Novartis Investigative Site	Barretos	SP	Brazil	14784 400
18	Novartis Investigative Site	Sao Paulo	SP	Brazil	01327 001
19	Novartis Investigative Site	Sao Paulo	SP	Brazil	04502 001
20	Novartis Investigative Site	Sorocaba	SP	Brazil
21	Novartis Investigative Site	Rionegro	Antioquia	Colombia	054047
22	Novartis Investigative Site	Barranquilla	Atlantico	Colombia	080005
23	Novartis Investigative Site	Barranquilla		Colombia
24	Novartis Investigative Site	Colombes Cedex		France	92701
25	Novartis Investigative Site	Eaubonne		France	95600
26	Novartis Investigative Site	Nantes Cedex 1		France	44093
27	Novartis Investigative Site	Pessac		France	33604
28	Novartis Investigative Site	Pierre Benite		France	69495
29	Novartis Investigative Site	Lubeck		Germany	23538
30	Novartis Investigative Site	Muenchen		Germany	81377
31	Novartis Investigative Site	Nuernberg		Germany	90419
32	Novartis Investigative Site	México	Distrito Federal	Mexico	14050
33	Novartis Investigative Site	Ciudad de Mexico	Mexico CP	Mexico	14080
34	Novartis Investigative Site	Estado de Mexico		Mexico	52787
35	Novartis Investigative Site	San Isidro	Lima	Peru	27
36	Novartis Investigative Site	San Miguel	Lima	Peru	32
37	Novartis Investigative Site	Lima		Peru	10
38	Novartis Investigative Site	Lima		Peru	1
39	Novartis Investigative Site	Barnaul		Russian Federation	656045
40	Novartis Investigative Site	Moscow		Russian Federation	111539
41	Novartis Investigative Site	Moscow		Russian Federation	123056
42	Novartis Investigative Site	Ryazan		Russian Federation	390039
43	Novartis Investigative Site	S-Petersburg		Russian Federation	194354
44	Novartis Investigative Site	Saint Petersburg		Russian Federation	194044
45	Novartis Investigative Site	Saint Petersburg		Russian Federation	199106
46	Novartis Investigative Site	Sestroretsk		Russian Federation	197706
47	Novartis Investigative Site	St Petersburg		Russian Federation	193312
48	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
49	Novartis Investigative Site	Barcelona	Cataluna	Spain	08035
50	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
51	Novartis Investigative Site	Madrid		Spain	28031
52	Novartis Investigative Site	Madrid		Spain	28034
53	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
54	Novartis Investigative Site	Ankara		Turkey	06100
55	Novartis Investigative Site	Istanbul		Turkey
56	Novartis Investigative Site	Yenisehir/Izmir		Turkey	35110
57	Novartis Investigative Site	Harrow		United Kingdom	HA1 3UJ
58	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
59	Novartis Investigative Site	London		United Kingdom	SE5 9RS
60	Novartis Investigative Site	London		United Kingdom	WC1E 6HX
61	Novartis Investigative Site	Manchester		United Kingdom	M13 9PL

Sponsors and Collaborators

• Novartis Pharmaceuticals
• Incyte Corporation

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - May 20, 2020
• Statistical Analysis Plan - Nov 24, 2020

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04362137
• Other Study ID Numbers: CINC424J12301; INCB 18424-368; 2020-001662-11
• First Posted: Apr 24, 2020
• Last Update Posted: Oct 11, 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
• Keywords provided by Novartis Pharmaceuticals: COVID-19 pneumonia; cytokine release syndrome; SARS-COV-2; ruxolitinib
• Additional relevant MeSH terms: COVID-19; Cytokine Release Syndrome

Study Results

Participant Flow

Recruitment Details	Participants took part in 61 investigative sites in 12 countries.
Pre-assignment Detail	Patients were to be randomized on the same day as screening or up to 2 days after completing the screening procedures.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Period Title: Overall Study
STARTED	287	145
Safety Set	281	143
COMPLETED	269	139
NOT COMPLETED	18	6

Baseline Characteristics

Arm/Group Title	Ruxolitinib 5 mg	Placebo	Total
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days	Total of all reporting groups
Overall Participants	287	145	432
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.4 (13.7)	56.9 (12.5)	56.5 (13.3)
Sex: Female, Male (Count of Participants)
Female	125 43.6%	72 49.7%	197 45.6%
Male	162 56.4%	73 50.3%	235 54.4%
Race/Ethnicity, Customized (Count of Participants)
White	242 84.3%	109 75.2%	351 81.3%
American Indian Or Alaska Native	26 9.1%	13 9%	39 9%
Black Or African American	6 2.1%	9 6.2%	15 3.5%
Asian	5 1.7%	5 3.4%	10 2.3%
Multiple	3 1%	2 1.4%	5 1.2%
Unknown	5 1.7%	7 4.8%	12 2.8%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care
Description	Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis.
Time Frame	Day 1 - Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants excluding those who developed respiratory failure and/or required ICU at randomization.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	284	144
Count of Participants [Participants]	34 11.8%	17 11.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.769
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio < 1 favors the ruxolitinib 5 mg arm

2. Secondary Outcome

Title	Clinical Status
Description	Clinical status is measured with the 9-point ordinal scale. The scoring is: Uninfected patients have a score 0 (no clinical or virological evidence of infection). Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as peripheral oxygen saturation (SpO2) ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). Patients who die have a score 8.
Time Frame	Baseline, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment for the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Baseline	3.7 (0.56)	3.7 (0.53)
Day 15	1.8 (1.54)	1.8 (1.41)
Day 29	1.1 (1.61)	1.0 (1.41)

3. Secondary Outcome

Title	Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status
Description	Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.
Time Frame	Baseline, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment of clinical status at baseline.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Day 15	206 71.8%	108 74.5%
Day 29	252 87.8%	129 89%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.647
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio > 1 favors the ruxolitinib 5 mg arm

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 29
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio > 1 favors the ruxolitinib 5 mg arm

4. Secondary Outcome

Title	Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status
Description	Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.
Time Frame	Baseline, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment of clinical status at baseline.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Day 15	250 87.1%	128 88.3%
Day 29	261 90.9%	136 93.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.946
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio > 1 favors the ruxolitinib 5 mg arm

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 29
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.573
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.35 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio > 1 favors the ruxolitinib 5 mg arm

5. Secondary Outcome

Title	Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status
Description	Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.
Time Frame	Baseline, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment of clinical status at baseline.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Day 15	16 5.6%	9 6.2%
Day 29	14 4.9%	5 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.532
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio < 1 favors the ruxolitinib 5 mg arm

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 29
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.764
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.40 to 3.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio < 1 favors the ruxolitinib 5 mg arm

6. Secondary Outcome

Title	Time to Improvement in Clinical Status
Description	Time to improvement in clinical status from baseline category to one less severe category of the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Median time to improvement is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who did not achieve improvement and did not die are censored at their last clinical status assessment date.
Time Frame	29 days

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment of clinical status at baseline.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Median (95% Confidence Interval) [days]	9.0	9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.330
	Comments
	Method	Proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Between group comparison using competing risk framework. A hazard ratio > 1 favors the ruxolitinib 5 mg arm

7. Secondary Outcome

Title	Mean Change From Baseline in the Clinical Status
Description	Mean change from baseline in the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. A negative change from baseline in the clinical status is a favorable outcome.
Time Frame	Baseline, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment for the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Day 15	-1.96 (0.084)	-1.93 (0.118)
Day 29	-2.61 (0.090)	-2.69 (0.126)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.831
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) mean
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.144
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 29
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.624
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.23 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.155
	Estimation Comments

8. Secondary Outcome

Title	Mortality Rate
Description	Mortality rate is determined as the proportion of participants who died by study Day 15 and Day 29
Time Frame	Day 15, Day 29

Outcome Measure Data

Analysis Population Description

All randomized participants including those who did not receive any dose, as per intent-to-treat principle, and excluding patients lost to follow up.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Day 15	6 2.1%	2 1.4%
Day 29	9 3.1%	3 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.944
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.20 to 5.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio < 1 favors the ruxolitinib 5 mg arm

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 29
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.775
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.35 to 5.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio < 1 favors the ruxolitinib 5 mg arm

9. Secondary Outcome

Title	Proportion of Patients Requiring Mechanical Ventilation
Description	Proportion of patients requiring mechanical ventilation. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who required mechanical ventilation at randomization are excluded from the analysis.
Time Frame	Day 1 - Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment for the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Count of Participants [Participants]	22 7.7%	10 6.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.45 to 2.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio < 1 favors the ruxolitinib 5 mg arm

10. Secondary Outcome

Title	Duration of Hospitalization
Description	Duration of hospitalization is defined as time to hospital discharge. Median time to hospital discharge is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who were not discharged and did not die are censored at their last assessment date.
Time Frame	29 days

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment for the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Median (95% Confidence Interval) [days]	9.0	9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.738
	Comments
	Method	Proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Between group comparison using competing risk framework. A hazard ratio > 1 favors the ruxolitinib 5 mg arm

11. Secondary Outcome

Title	Time to Hospital Discharge or to a NEWS2 Score of ≤2
Description	The time to hospital discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). Median time is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study.
Time Frame	29 days

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment for the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	286	145
Median (95% Confidence Interval) [days]	4.0	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.869
	Comments
	Method	Proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Between group comparison using competing risk framework. A hazard ratio > 1 favors the ruxolitinib 5 mg arm

12. Secondary Outcome

Title	Change From Baseline in NEWS2 Score
Description	The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). At each visit, only patients with a value at both baseline and the respective visit are included. A negative change from baseline in NEWS2 score is a favorable outcome.
Time Frame	Baseline, Days 3, 5, 8, 11, 15, and 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment for the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Day 3	-0.7 (1.91)	-0.6 (2.13)
Day 5	-1.0 (2.02)	-0.8 (2.19)
Day 8	-1.3 (2.25)	-1.3 (2.60)
Day 11	-1.1 (2.70)	-1.3 (2.74)
Day 15	-1.9 (2.34)	-2.2 (2.35)
Day 29	-2.3 (2.37)	-2.5 (2.17)

13. Secondary Outcome

Title	Change From Baseline in SpO2/FiO2 Ratio
Description	Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio). At each visit, only patients with a value at both baseline and the respective visit are included. A positive change from baseline in SpO2/FiO2 ratio is a favorable outcome.
Time Frame	Baseline, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment of the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Day 15	90.110 (104.4783)	106.766 (100.9778)
Day 29	105.553 (98.2452)	109.710 (95.4279)

14. Secondary Outcome

Title	Proportion of Patients With no Oxygen Therapy
Description	Proportion of patients with no oxygen therapy (defined as oxygen saturation ≥ 94% on room air) at Days 15 and 29. Analyses are cumulative, thus analysis on each day includes all events till that day. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis.
Time Frame	Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Randomized participants with a valid assessment of the outcome measure.

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Day 15	255 88.9%	133 91.7%
Day 29	262 91.3%	136 93.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.325
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.23 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio > 1 favors the ruxolitinib 5 mg arm

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5 mg, Placebo
	Comments	Day 29
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.25 to 5.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison is ruxolitinib 5 mg/placebo. An odds ratio > 1 favors the ruxolitinib 5 mg arm

15. Post-Hoc Outcome

Title	All Collected Deaths
Description	Deaths in the safety population were evaluated in all participants who received at least one dose of double-blind treatment. Total deaths were evaluated in all participants randomized.
Time Frame	29 days

Outcome Measure Data

Analysis Population Description

Clinical database population - all randomized participants

Arm/Group Title	Ruxolitinib 5 mg	Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days	Matching-image placebo for 14 days with possible extension of treatment to 28 days
Measure Participants	287	145
Deaths in the safety population	9 3.1%	3 2.1%
Total deaths	9 3.1%	3 2.1%

Adverse Events

Time Frame	From first dose of double-blind treatment and up to the last study visit (Day 29).
Adverse Event Reporting Description	Adverse events are considered as treatment-emergent if the event started after the first dose of double-blind treatment or the event was present prior to start of double-blind treatment but increased in severity based on preferred term and up to the last study visit (Day 29). Adverse events and all-cause mortality are evaluated in the Safety Set that includes all participants who received at least one dose of double-blind treatment.
Arm/Group Title	Ruxolitinib 5 mg		Placebo
Arm/Group Description	Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days		Matching-image placebo for 14 days with possible extension of treatment to 28 days
All Cause Mortality
	Ruxolitinib 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/281 (3.2%)		3/143 (2.1%)
Serious Adverse Events
	Ruxolitinib 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/281 (11%)		15/143 (10.5%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/281 (0.4%)		0/143 (0%)
Cardiac disorders
Adams-Stokes syndrome	1/281 (0.4%)		0/143 (0%)
Atrial fibrillation	1/281 (0.4%)		0/143 (0%)
Cardiac arrest	1/281 (0.4%)		0/143 (0%)
Cardiopulmonary failure	0/281 (0%)		1/143 (0.7%)
Ear and labyrinth disorders
Vertigo	0/281 (0%)		1/143 (0.7%)
Gastrointestinal disorders
Pancreatitis	1/281 (0.4%)		0/143 (0%)
General disorders
Adverse event	1/281 (0.4%)		0/143 (0%)
General physical health deterioration	1/281 (0.4%)		0/143 (0%)
Multiple organ dysfunction syndrome	1/281 (0.4%)		1/143 (0.7%)
Performance status decreased	1/281 (0.4%)		0/143 (0%)
Infections and infestations
Antibiotic associated colitis	1/281 (0.4%)		0/143 (0%)
Bacteraemia	1/281 (0.4%)		0/143 (0%)
COVID-19	8/281 (2.8%)		3/143 (2.1%)
COVID-19 pneumonia	1/281 (0.4%)		0/143 (0%)
Escherichia bacteraemia	0/281 (0%)		1/143 (0.7%)
Pneumonia	3/281 (1.1%)		0/143 (0%)
Pneumonia fungal	1/281 (0.4%)		0/143 (0%)
Urinary tract infection	0/281 (0%)		1/143 (0.7%)
Injury, poisoning and procedural complications
Endotracheal intubation complication	1/281 (0.4%)		0/143 (0%)
Fall	0/281 (0%)		1/143 (0.7%)
Investigations
Alanine aminotransferase increased	0/281 (0%)		1/143 (0.7%)
Transaminases increased	0/281 (0%)		1/143 (0.7%)
Nervous system disorders
Cerebral infarction	1/281 (0.4%)		0/143 (0%)
Hypoglycaemic coma	1/281 (0.4%)		0/143 (0%)
Ischaemic stroke	1/281 (0.4%)		0/143 (0%)
Psychiatric disorders
Mental status changes	1/281 (0.4%)		0/143 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/281 (0.4%)		1/143 (0.7%)
Acute respiratory failure	4/281 (1.4%)		1/143 (0.7%)
Dyspnoea	1/281 (0.4%)		0/143 (0%)
Hypoxia	4/281 (1.4%)		4/143 (2.8%)
Pneumothorax	1/281 (0.4%)		0/143 (0%)
Pulmonary fibrosis	1/281 (0.4%)		0/143 (0%)
Respiratory disorder	1/281 (0.4%)		0/143 (0%)
Respiratory distress	1/281 (0.4%)		0/143 (0%)
Respiratory failure	2/281 (0.7%)		2/143 (1.4%)
Vascular disorders
Deep vein thrombosis	1/281 (0.4%)		0/143 (0%)
Shock	1/281 (0.4%)		0/143 (0%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/281 (40.2%)		62/143 (43.4%)
Blood and lymphatic system disorders
Leukocytosis	4/281 (1.4%)		4/143 (2.8%)
Neutropenia	6/281 (2.1%)		4/143 (2.8%)
Thrombocytosis	6/281 (2.1%)		3/143 (2.1%)
Gastrointestinal disorders
Abdominal pain	4/281 (1.4%)		4/143 (2.8%)
Constipation	9/281 (3.2%)		7/143 (4.9%)
Diarrhoea	21/281 (7.5%)		12/143 (8.4%)
Nausea	6/281 (2.1%)		11/143 (7.7%)
General disorders
Asthenia	6/281 (2.1%)		0/143 (0%)
Fatigue	10/281 (3.6%)		2/143 (1.4%)
Pyrexia	6/281 (2.1%)		2/143 (1.4%)
Infections and infestations
Urinary tract infection	3/281 (1.1%)		4/143 (2.8%)
Investigations
Alanine aminotransferase increased	17/281 (6%)		6/143 (4.2%)
Aspartate aminotransferase increased	5/281 (1.8%)		3/143 (2.1%)
Transaminases increased	7/281 (2.5%)		2/143 (1.4%)
Metabolism and nutrition disorders
Hyperglycaemia	4/281 (1.4%)		5/143 (3.5%)
Hyperkalaemia	6/281 (2.1%)		6/143 (4.2%)
Hypokalaemia	8/281 (2.8%)		7/143 (4.9%)
Hyponatraemia	1/281 (0.4%)		3/143 (2.1%)
Hypoproteinaemia	4/281 (1.4%)		3/143 (2.1%)
Nervous system disorders
Dizziness	2/281 (0.7%)		4/143 (2.8%)
Headache	23/281 (8.2%)		11/143 (7.7%)
Psychiatric disorders
Anxiety	6/281 (2.1%)		1/143 (0.7%)
Insomnia	3/281 (1.1%)		4/143 (2.8%)
Respiratory, thoracic and mediastinal disorders
Cough	12/281 (4.3%)		3/143 (2.1%)
Dyspnoea	3/281 (1.1%)		3/143 (2.1%)
Vascular disorders
Hypertension	4/281 (1.4%)		3/143 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.