STRIDE-3: A Long-Term, Open-Label Study to Evaluate the Safety of Sitaxsentan Sodium Treatment in Patients With Pulmonary Arterial Hypertension

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00811018
• Collaborator: (none)
• Enrollment: 1,192
• Locations: 91
• Arm: 1
• Duration (Months): 100
• Patients Per Site: 13.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multi-center, open-label study of sitaxsentan sodium 100 mg taken orally once daily by subjects with PAH until sitaxsentan, in a particular country or region, is commercially available for the treatment of PAH or the study is closed.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Sitaxsentan	Phase 3

Detailed Description

Open-label extension

Study Design

• Study Type: Interventional
• Actual Enrollment: 1192 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: A Long-Term, Open-Label Study To Evaluate The Safety Of Sitaxsentan Sodium Treatment In Patients With Pulmonary Arterial Hypertension
• Study Start Date: Mar 1, 2003
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sitaxsentan Sitaxsentan	Drug: Sitaxsentan; Sitaxsentan 100 mg tablets once daily; Other Names: Sitaxentan

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to 82 months]

   All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product were reported.

2. The Percentage of Participants Who Experience an Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Value Greater Than (>) 3.0 Times (x) the Upper Limit of Normal Range (ULN) [Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months]

   ALT and AST data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

3. The Percentage of Participants Who Experience an ALT and AST Value > 3.0 x ULN [Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months]

   ALT and AST data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

4. Percentage of Participants With Total Bilirubin > 1.5 x ULN [Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months]

   Total builirubin data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

5. Percentage of Participants With Laboratory Test Abnormalities (Hematology) [Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months]

   Hematology data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

6. Percentage of Participants With Laboratory Test Abnormalities (Chemistry) [Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months]

   Chemistry data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

7. Percentage of Participants With Laboratory Test Abnormalities (Urinalysis) [Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months]

   Urinalysis data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

8. Percentage of Participants With Anticoagulant Use [Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months]

   Participants with anticoagulant use before first dose or participants with anticoagulant use from first dose of sitaxsentan.

9. Percentage of Participants With Elevated International Normalize Ratio (INR) [Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months]

   Elevated INR in participants who took warfarin, warfarin derivatives, other anticoagulant and no anticoagulants. Elevated INR defined as > 3.5. Percentage calculated using number of participants with INR data as the denominator.

10. Percentage of Participants With Electrocardiography (ECG) Results of Potential Clinical Importance [Weeks 28,60,72,84,96,104, Transition Visit up to 82 months]

    Standard 12-lead ECG results determined to be of potential clinical importance according to investigator clinical judgement.

11. Percentage of Participants With Vital Sign Results of Potential Clinical Importance [Day 1, Weeks 28,60,72,84,96,104, Transition visit, every 6 months Post Transition, up to 82 months]

    Vital signs include sitting blood pressure, respiration rate, heart rate and temperature. Potential clinical importance determined according to investigator clinical judgement.

12. Percentage of Participants With Abnormal Prothrombin Time (PT) [Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months]

    PT data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

13. Percentage of Participants With Abnormal Partial Thromboplastin Time (PTT) [Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months]

    PTT data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Pulmonary Arterial Hypertension (PAH) confirmed by cardiac catheterization.

• Current diagnosis of WHO group 1 PAH with functional class 2, 3, or 4 symptoms.

Exclusion Criteria:

• Has portal hypertension or chronic liver disease.

• Has history of left sided heart disease or significant cardiac disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Birmingham	Alabama	United States	35233
2	Pfizer Investigational Site	Birmingham	Alabama	United States	35294
3	Pfizer Investigational Site	Phoenix	Arizona	United States	85013
4	Pfizer Investigational Site	Los Angeles	California	United States	90073
5	Pfizer Investigational Site	San Francisco	California	United States	94143-0124
6	Pfizer Investigational Site	Torrence	California	United States	90502
7	Pfizer Investigational Site	Denver	Colorado	United States	80218
8	Pfizer Investigational Site	Denver	Colorado	United States	80262
9	Pfizer Investigational Site	Sarasota	Florida	United States	34233
10	Pfizer Investigational Site	Atlanta	Georgia	United States	30322
11	Pfizer Investigational Site	Augusta	Georgia	United States	30912
12	Pfizer Investigational Site	Decatur	Georgia	United States	30030
13	Pfizer Investigational Site	Decatur	Georgia	United States	30033
14	Pfizer Investigational Site	Chicago	Illinois	United States	60637
15	Pfizer Investigational Site	Kansas City	Kansas	United States	66160
16	Pfizer Investigational Site	Lexington	Kentucky	United States	40536
17	Pfizer Investigational Site	New Orleans	Louisiana	United States	70112-1393
18	Pfizer Investigational Site	New Orleans	Louisiana	United States	70112
19	Pfizer Investigational Site	Portland	Maine	United States	04102
20	Pfizer Investigational Site	Baltimore	Maryland	United States	21205
21	Pfizer Investigational Site	Boston	Massachusetts	United States	02111
22	Pfizer Investigational Site	Boston	Massachusetts	United States	02114
23	Pfizer Investigational Site	Boston	Massachusetts	United States	02118
24	Pfizer Investigational Site	Boston	Massachusetts	United States	02218
25	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48109-0570
26	Pfizer Investigational Site	Detroit	Michigan	United States	48201
27	Pfizer Investigational Site	Rochester	Minnesota	United States	55905
28	Pfizer Investigational Site	New Brunswick	New Jersey	United States	08903-0019
29	Pfizer Investigational Site	New York	New York	United States	10032
30	Pfizer Investigational Site	Durham	North Carolina	United States	27710
31	Pfizer Investigational Site	Cleveland	Ohio	United States	44106
32	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
33	Pfizer Investigational Site	Columbus	Ohio	United States	43210
34	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19140
35	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15213
36	Pfizer Investigational Site	Charleston	South Carolina	United States	29425
37	Pfizer Investigational Site	Nashville	Tennessee	United States	37232-2650
38	Pfizer Investigational Site	Nashville	Tennessee	United States	37232-5735
39	Pfizer Investigational Site	Nashville	Tennessee	United States	37232
40	Pfizer Investigational Site	Galveston	Texas	United States	77555-0561
41	Pfizer Investigational Site	Houston	Texas	United States	77030
42	Pfizer Investigational Site	San Antonio	Texas	United States	78229
43	Pfizer Investigational Site	Salt Lake City	Utah	United States	84143
44	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53215
45	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53226
46	Pfizer Investigational Site	Capital Federal	Buenos Aires	Argentina	C1416ASA
47	Pfizer Investigational Site	Capital Federal		Argentina	C1039AAO
48	Pfizer Investigational Site	Darlinghurst	New South Wales	Australia	2010
49	Pfizer Investigational Site	Chermside Q	Queensland	Australia	4032
50	Pfizer Investigational Site	Melbourne	Victoria	Australia	3004
51	Pfizer Investigational Site	Chermside		Australia	QLD 4032
52	Pfizer Investigational Site	Graz		Austria	8036
53	Pfizer Investigational Site	Wien		Austria	1090
54	Pfizer Investigational Site	Bruxelles		Belgium	1070
55	Pfizer Investigational Site	Leuven		Belgium	B - 3000
56	Pfizer Investigational Site	Belo Horizonte	MG	Brazil	30380-090
57	Pfizer Investigational Site	Porto Alegre	RS	Brazil	90035-003
58	Pfizer Investigational Site	Sao Paulo		Brazil	05403-000
59	Pfizer Investigational Site	Calgary	Alberta	Canada	T1Y 6J4
60	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 2B7
61	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V5Z 1M9
62	Pfizer Investigational Site	London	Ontario	Canada	N6A 4G5
63	Pfizer Investigational Site	Toronto	Ontario	Canada	M5G 2C4
64	Pfizer Investigational Site	Montreal	Quebec	Canada	H3T 1E2
65	Pfizer Investigational Site	Quebec		Canada	G1V 4G5
66	Pfizer Investigational Site	Clamart Cedex		France	92141
67	Pfizer Investigational Site	GRENOBLE Cedex 09		France	38043
68	Pfizer Investigational Site	Strasbourg		France	67098
69	Pfizer Investigational Site	Berlin		Germany	14050
70	Pfizer Investigational Site	Dresden		Germany	01307
71	Pfizer Investigational Site	Giessen		Germany	35392
72	Pfizer Investigational Site	Greifswald		Germany	17487
73	Pfizer Investigational Site	Hannover		Germany	30625
74	Pfizer Investigational Site	Heidelberg		Germany	69120
75	Pfizer Investigational Site	Leipzig		Germany	04103
76	Pfizer Investigational Site	Regensburg		Germany	93053
77	Pfizer Investigational Site	Petach Tikva		Israel	49100
78	Pfizer Investigational Site	Tel-Hashomer, Ramat Gan		Israel	52601
79	Pfizer Investigational Site	Bologna		Italy	40138
80	Pfizer Investigational Site	Monterrey	CP	Mexico	64020
81	Pfizer Investigational Site	Tlalpan	DF	Mexico	14080
82	Pfizer Investigational Site	Monterrey	N.l.	Mexico	64360
83	Pfizer Investigational Site	Amsterdam		Netherlands	1081 HV
84	Pfizer Investigational Site	Krakow		Poland	31-202
85	Pfizer Investigational Site	Warszawa		Poland	01-138
86	Pfizer Investigational Site	Zabrze		Poland	41-800
87	Pfizer Investigational Site	Barcelona		Spain	08036
88	Pfizer Investigational Site	Papworth Everard	Cambridgeshire	United Kingdom	CB3 8RB
89	Pfizer Investigational Site	Glasgow		United Kingdom	G11 6NT
90	Pfizer Investigational Site	London		United Kingdom	NW3 2QG
91	Pfizer Investigational Site	Newcastle		United Kingdom	NE7 7DN

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00811018
• Other Study ID Numbers: B1321007; FPH03
• First Posted: Dec 18, 2008
• Last Update Posted: Apr 24, 2012
• Last Verified: Nov 1, 2011

• Keywords provided by Pfizer: Open-label study
• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Sitaxsentan

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from studies FPH02/FPH02-X (STRIDE 2/STRIDE 2 Extension [NCT00080457, NCT00593905]), FPH04 (STRIDE 4), FPH06 (STRIDE 6) or were naive to sitaxsentan sodium.

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Period Title: Overall Study
STARTED	1192
COMPLETED	224
NOT COMPLETED	968

Baseline Characteristics

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Overall Participants	1192
Age, Customized (participants) [Number]
less than (<) 18 years	35 2.9%
18-44 years	433 36.3%
45-64 years	468 39.3%
greater than or equal to 65 years	256 21.5%
Sex: Female, Male (Count of Participants)
Female	914 76.7%
Male	278 23.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product were reported.
Time Frame	Day 1 up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population: all enrolled participants who took at least one dose of sitaxsentan 100 mg during the study

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	1192
AEs	1150 96.5%
SAEs	586 49.2%

2. Primary Outcome

Title	The Percentage of Participants Who Experience an Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Value Greater Than (>) 3.0 Times (x) the Upper Limit of Normal Range (ULN)
Description	ALT and AST data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	1192
> 3 x ULN and less than or equal to (<=) 5x ULN	5.12 0.4%
> 5 x ULN and <= 8 x ULN	4.45 0.4%
> 8 x ULN and <= 10 x ULN	0.76 0.1%
> 10 x ULN	2.60 0.2%

3. Primary Outcome

Title	The Percentage of Participants Who Experience an ALT and AST Value > 3.0 x ULN
Description	ALT and AST data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	1192
> 3 x ULN and <= 5 x ULN	3.94 0.3%
> 5 x ULN and <= 8 x ULN	2.60 0.2%
> 8 x ULN and <= 10 x ULN	0.67 0.1%
> 10 x ULN	1.26 0.1%

4. Primary Outcome

Title	Percentage of Participants With Total Bilirubin > 1.5 x ULN
Description	Total builirubin data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	1192
>= 1.5 x ULN and <2 x ULN	10.23 0.9%
>= 2 x ULN and < 3x ULN	6.80 0.6%
>= 3x ULN	5.03 0.4%

5. Primary Outcome

Title	Percentage of Participants With Laboratory Test Abnormalities (Hematology)
Description	Hematology data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population; N=number of participants with normal observation at baseline; n=number of participants with normal baseline and an abnormality meeting specific criteria for the specific lab

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	814
Basophiles (n=814)	4.1 0.3%
Eosinophiles % (n=3)	100 8.4%
Eosinophils (n=785)	20.6 1.7%
Hematocrit (n=537)	46.2 3.9%
Hemoglobin (n=573)	48.7 4.1%
Lymphocytes (n=737)	35.5 3%
Mean Corpuscular Hemoglobin (n=56)	21.4 1.8%
Mean Corpuscular Hemoglobin Concentration (n=59)	33.9 2.8%
Mean Corpuscular Volume (n=65)	27.7 2.3%
Monocytes (n=766)	28.3 2.4%
Neutrophiles (n=728)	38 3.2%
Platelets Count (n=719)	26.3 2.2%
Red Blood Cells (n=542)	39.1 3.3%
White Blood Cells (n=730)	35.3 3%

6. Primary Outcome

Title	Percentage of Participants With Laboratory Test Abnormalities (Chemistry)
Description	Chemistry data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population; N=number of participants with normal observation at baseline; n=number of participants with normal baseline and an abnormality meeting specific criteria for the specific lab

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	839
Albumin (n=33)	45.5 3.8%
Alkaline Phosphatase (n=593)	45.5 3.8%
ALT (n=839)	36.1 3%
Amylase (n=9)	0 0%
AST (n=814)	49.4 4.1%
Bicarbonate (n=540)	56.7 4.8%
Blood urea nitrogen (BUN) (n=615)	42.4 3.6%
Calcium (n=819)	21.4 1.8%
Chloride (n=804)	31 2.6%
Creatinine (n=808)	25 2.1%
Direct Bilirubin (n=11)	54.5 4.6%
Gamma glutamyltransferase (GGT) (n=22)	45.5 3.8%
Glucose (n=674)	61.6 5.2%
Glucose-fasting (n=2)	50 4.2%
Indirect Bilirubin (n=11)	45.5 3.8%
Phosphorus (n=740)	50.8 4.3%
Potassium (n=749)	51.8 4.3%
Sodium (n=811)	29.1 2.4%
Total Bilirubin (n=726)	27.7 2.3%
Total Protein (n=738)	38.1 3.2%
Urea (n=35)	48.6 4.1%
Uric Acid (n=415)	46.5 3.9%

7. Primary Outcome

Title	Percentage of Participants With Laboratory Test Abnormalities (Urinalysis)
Description	Urinalysis data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 62, 68, 72, 74, 80, 84, 88, 92, 96, 100, 104, 108 and every 4 weeks to Termination up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population; N=number of participants with normal observation at baseline; n=number of participants with normal baseline and an abnormality meeting specific criteria for the specific lab

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	789
PH (n=789)	0 0%
Specific Gravity (n=787)	1.8 0.2%

8. Primary Outcome

Title	Percentage of Participants With Anticoagulant Use
Description	Participants with anticoagulant use before first dose or participants with anticoagulant use from first dose of sitaxsentan.
Time Frame	Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	1192
Warfarin before first dose	39.77 3.3%
Warfarin Derivatives before first dose	19.13 1.6%
Other Anticoagulants before first dose	2.01 0.2%
Warfarin from first dose/data cut off	58.22 4.9%
Warfarin Derivatives from first dose/data cut off	20.55 1.7%
Other Anticoagulants from first dose/data cut off	2.52 0.2%

9. Primary Outcome

Title	Percentage of Participants With Elevated International Normalize Ratio (INR)
Description	Elevated INR in participants who took warfarin, warfarin derivatives, other anticoagulant and no anticoagulants. Elevated INR defined as > 3.5. Percentage calculated using number of participants with INR data as the denominator.
Time Frame	Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	1192
INR <= 3.5; warfarin	20.97 1.8%
INR >3.5 and <=5; warfarin	17.70 1.5%
INR >5 and <=9; warfarin	12.75 1.1%
INR > 9; warfarin	3.44 0.3%
INR <=3.5; warfarin derivatives	4.95 0.4%
INR >3.5 and <=5; warfarin derivatives	6.96 0.6%
INR >5 and <=9; warfarin derivatives	5.96 0.5%
INR >9; warfarin derivatives	1.85 0.2%
INR <=3.5; other anticoagulant	1.34 0.1%
INR >3.5 and <=5; other anticoagulant	0.59 0%
INR >5 and <= 9; other anticoagulant	0.50 0%
INR <=3.5; no anticoagulant	19.55 1.6%
INR >3.5 and <= 5; no anticoagulant	0.17 0%
INR >5 and <=9; no anticoagulant	0.42 0%
INR >9; no anticoagulant	0.25 0%

10. Primary Outcome

Title	Percentage of Participants With Electrocardiography (ECG) Results of Potential Clinical Importance
Description	Standard 12-lead ECG results determined to be of potential clinical importance according to investigator clinical judgement.
Time Frame	Weeks 28,60,72,84,96,104, Transition Visit up to 82 months

Outcome Measure Data

Analysis Population Description

Data not summarized, study terminated early

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	0

11. Primary Outcome

Title	Percentage of Participants With Vital Sign Results of Potential Clinical Importance
Description	Vital signs include sitting blood pressure, respiration rate, heart rate and temperature. Potential clinical importance determined according to investigator clinical judgement.
Time Frame	Day 1, Weeks 28,60,72,84,96,104, Transition visit, every 6 months Post Transition, up to 82 months

Outcome Measure Data

Analysis Population Description

Data not summarized, study terminated early

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	0

12. Primary Outcome

Title	Percentage of Participants With Abnormal Prothrombin Time (PT)
Description	PT data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months

Outcome Measure Data

Analysis Population Description

Data not summarized, study terminated early

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	0

13. Primary Outcome

Title	Percentage of Participants With Abnormal Partial Thromboplastin Time (PTT)
Description	PTT data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analysis.
Time Frame	Baseline, Weeks 1 and 2, every 2 weeks up to Week 52, Amendment 4 visit, every 4 weeks up to 82 months

Outcome Measure Data

Analysis Population Description

Data not summarized, study terminated early

Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sitaxsentan
Arm/Group Description	All participants received sitaxsentan 100 milligrams (mg) orally once daily beginning on Study Day 1 to termination from study.
All Cause Mortality
	Sitaxsentan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sitaxsentan
	Affected / at Risk (%)	# Events
Total	586/1192 (49.2%)
Blood and lymphatic system disorders
Anaemia	16/1192 (1.3%)
Haemorrhagic anaemia	1/1192 (0.1%)
Hypochromic anaemia	1/1192 (0.1%)
Iron deficiency anaemia	1/1192 (0.1%)
Microcytic anaemia	2/1192 (0.2%)
Splenomegaly	1/1192 (0.1%)
Thrombocytopenia	2/1192 (0.2%)
Cardiac disorders
Acute myocardial infarction	3/1192 (0.3%)
Angina pectoris	2/1192 (0.2%)
Angina unstable	2/1192 (0.2%)
Arrhythmia	3/1192 (0.3%)
Atrial fibrillation	16/1192 (1.3%)
Atrial flutter	15/1192 (1.3%)
Atrial tachycardia	1/1192 (0.1%)
Bradycardia	5/1192 (0.4%)
Cardiac aneurysm	1/1192 (0.1%)
Cardiac arrest	8/1192 (0.7%)
Cardiac disorder	1/1192 (0.1%)
Cardiac failure	26/1192 (2.2%)
Cardiac failure congestive	14/1192 (1.2%)
Cardiac pseudoaneurysm	1/1192 (0.1%)
Cardiac tamponade	2/1192 (0.2%)
Cardio-respiratory arrest	2/1192 (0.2%)
Cardiogenic shock	5/1192 (0.4%)
Cor pulmonale	7/1192 (0.6%)
Cor pulmonale acute	1/1192 (0.1%)
Coronary artery disease	1/1192 (0.1%)
Coronary artery occlusion	1/1192 (0.1%)
Intracardiac thrombus	1/1192 (0.1%)
Low cardiac output syndrome	1/1192 (0.1%)
Myocardial infarction	9/1192 (0.8%)
Myocardial ischaemia	2/1192 (0.2%)
Palpitations	1/1192 (0.1%)
Pericardial effusion	6/1192 (0.5%)
Right atrial dilatation	1/1192 (0.1%)
Right ventricular failure	68/1192 (5.7%)
Sick sinus syndrome	1/1192 (0.1%)
Sinus tachycardia	1/1192 (0.1%)
Supraventricular tachyarrhythmia	1/1192 (0.1%)
Supraventricular tachycardia	7/1192 (0.6%)
Tachyarrhythmia	1/1192 (0.1%)
Tachycardia	1/1192 (0.1%)
Ventricular arrhythmia	2/1192 (0.2%)
Ventricular dysfunction	3/1192 (0.3%)
Ventricular failure	1/1192 (0.1%)
Ventricular fibrillation	3/1192 (0.3%)
Ventricular tachycardia	3/1192 (0.3%)
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis	2/1192 (0.2%)
Ear and labyrinth disorders
Deafness	1/1192 (0.1%)
Endocrine disorders
Goitre	1/1192 (0.1%)
Eye disorders
Blindness	1/1192 (0.1%)
Glaucoma	1/1192 (0.1%)
Vitreous haemorrhage	1/1192 (0.1%)
Gastrointestinal disorders
Abdominal haematoma	1/1192 (0.1%)
Abdominal pain	6/1192 (0.5%)
Abdominal pain upper	1/1192 (0.1%)
Appendix disorder	1/1192 (0.1%)
Ascites	1/1192 (0.1%)
Dental caries	1/1192 (0.1%)
Diarrhoea	1/1192 (0.1%)
Duodenal ulcer haemorrhage	1/1192 (0.1%)
Dyspepsia	1/1192 (0.1%)
Epigastric discomfort	1/1192 (0.1%)
Gastric haemorrhage	1/1192 (0.1%)
Gastric ulcer haemorrhage	1/1192 (0.1%)
Gastritis	3/1192 (0.3%)
Gastritis erosive	1/1192 (0.1%)
Gastrointestinal haemorrhage	8/1192 (0.7%)
Gastrooesophageal reflux disease	1/1192 (0.1%)
Haematemesis	1/1192 (0.1%)
Haematochezia	2/1192 (0.2%)
Ileus	1/1192 (0.1%)
Inguinal hernia	1/1192 (0.1%)
Intestinal ischaemia	1/1192 (0.1%)
Intestinal obstruction	4/1192 (0.3%)
Large intestine perforation	3/1192 (0.3%)
Lower gastrointestinal haemorrhage	1/1192 (0.1%)
Melaena	4/1192 (0.3%)
Nausea	3/1192 (0.3%)
Oesophageal disorder	1/1192 (0.1%)
Oesophagitis	2/1192 (0.2%)
Pancreatic mass	1/1192 (0.1%)
Peritoneal haemorrhage	2/1192 (0.2%)
Peritonitis	2/1192 (0.2%)
Rectal haemorrhage	2/1192 (0.2%)
Small intestinal obstruction	2/1192 (0.2%)
Volvulus	1/1192 (0.1%)
Vomiting	4/1192 (0.3%)
General disorders
Asthenia	5/1192 (0.4%)
Cardiac death	1/1192 (0.1%)
Catheter related complication	2/1192 (0.2%)
Chest discomfort	2/1192 (0.2%)
Chest pain	25/1192 (2.1%)
Condition aggravated	1/1192 (0.1%)
Death	3/1192 (0.3%)
Device dislocation	2/1192 (0.2%)
Fatigue	3/1192 (0.3%)
Generalised oedema	2/1192 (0.2%)
Hyperpyrexia	1/1192 (0.1%)
Ill-defined disorder	1/1192 (0.1%)
Mass	1/1192 (0.1%)
Medical device complication	1/1192 (0.1%)
Multi-organ failure	4/1192 (0.3%)
Non-cardiac chest pain	2/1192 (0.2%)
Oedema	3/1192 (0.3%)
Oedema peripheral	3/1192 (0.3%)
Pain	2/1192 (0.2%)
Pyrexia	6/1192 (0.5%)
Sudden cardiac death	1/1192 (0.1%)
Sudden death	17/1192 (1.4%)
Systemic inflammatory response syndrome	2/1192 (0.2%)
Therapeutic response unexpected	1/1192 (0.1%)
Hepatobiliary disorders
Cholecystitis	8/1192 (0.7%)
Cholecystitis acute	3/1192 (0.3%)
Cholelithiasis	1/1192 (0.1%)
Gallbladder obstruction	1/1192 (0.1%)
Hepatic failure	1/1192 (0.1%)
Immune system disorders
Drug hypersensitivity	2/1192 (0.2%)
Infections and infestations
Abdominal infection	1/1192 (0.1%)
Abdominal sepsis	1/1192 (0.1%)
Acarodermatitis	1/1192 (0.1%)
Acute sinusitis	2/1192 (0.2%)
Appendicitis	5/1192 (0.4%)
Arthritis infective	1/1192 (0.1%)
Bacteraemia	1/1192 (0.1%)
Bacterial infection	1/1192 (0.1%)
Bacterial sepsis	1/1192 (0.1%)
Bronchitis	12/1192 (1%)
Bronchitis acute	3/1192 (0.3%)
Bronchopneumonia	5/1192 (0.4%)
Campylobacter infection	1/1192 (0.1%)
Catheter related infection	5/1192 (0.4%)
Catheter sepsis	4/1192 (0.3%)
Catheter site infection	6/1192 (0.5%)
Cellulitis	5/1192 (0.4%)
Central line infection	4/1192 (0.3%)
Chronic sinusitis	1/1192 (0.1%)
Cytomegalovirus infection	1/1192 (0.1%)
Dermo-hypodermitis	1/1192 (0.1%)
Device related infection	4/1192 (0.3%)
Diarrhoea infectious	2/1192 (0.2%)
Diverticulitis	3/1192 (0.3%)
Escherichia bacteraemia	1/1192 (0.1%)
Gastroenteritis	5/1192 (0.4%)
Gastroenteritis viral	1/1192 (0.1%)
Hepatitis B	1/1192 (0.1%)
Infected skin ulcer	1/1192 (0.1%)
Infection	1/1192 (0.1%)
Infectious mononucleosis	1/1192 (0.1%)
Klebsiella sepsis	1/1192 (0.1%)
Lobar pneumonia	2/1192 (0.2%)
Lower respiratory tract infection	2/1192 (0.2%)
Lung abscess	1/1192 (0.1%)
Lung infection	2/1192 (0.2%)
Mycobacterial infection	1/1192 (0.1%)
Osteomyelitis	1/1192 (0.1%)
Peritoneal abscess	1/1192 (0.1%)
Peritonsillitis	1/1192 (0.1%)
Pneumonia	65/1192 (5.5%)
Pneumonia klebsiella	1/1192 (0.1%)
Pseudomonal sepsis	2/1192 (0.2%)
Pseudomonas infection	1/1192 (0.1%)
Pyometra	1/1192 (0.1%)
Respiratory tract infection	4/1192 (0.3%)
Sepsis	7/1192 (0.6%)
Septic shock	4/1192 (0.3%)
Sinusitis	1/1192 (0.1%)
Subcutaneous abscess	1/1192 (0.1%)
Upper respiratory tract infection	4/1192 (0.3%)
Urinary tract infection	4/1192 (0.3%)
Urosepsis	2/1192 (0.2%)
Viral pericarditis	1/1192 (0.1%)
Wound infection	1/1192 (0.1%)
Injury, poisoning and procedural complications
Ankle fracture	2/1192 (0.2%)
Chest injury	1/1192 (0.1%)
Collapse of lung	1/1192 (0.1%)
Drug toxicity	2/1192 (0.2%)
Facial bones fracture	1/1192 (0.1%)
Fall	3/1192 (0.3%)
Femur fracture	1/1192 (0.1%)
Fracture	1/1192 (0.1%)
Gastroenteritis radiation	1/1192 (0.1%)
Head injury	2/1192 (0.2%)
Hip fracture	4/1192 (0.3%)
Humerus fracture	1/1192 (0.1%)
Intentional overdose	1/1192 (0.1%)
Joint dislocation	1/1192 (0.1%)
Joint injury	1/1192 (0.1%)
Lower limb fracture	1/1192 (0.1%)
Multiple fractures	1/1192 (0.1%)
Multiple injuries	1/1192 (0.1%)
Overdose	2/1192 (0.2%)
Pelvic fracture	1/1192 (0.1%)
Post procedural haemorrhage	2/1192 (0.2%)
Rib fracture	1/1192 (0.1%)
Road traffic accident	2/1192 (0.2%)
Spinal compression fracture	1/1192 (0.1%)
Subdural haematoma	5/1192 (0.4%)
Tibia fracture	1/1192 (0.1%)
Upper limb fracture	2/1192 (0.2%)
Investigations
Alanine aminotransferase increased	2/1192 (0.2%)
Angiogram	1/1192 (0.1%)
Apnoea test	1/1192 (0.1%)
Aspartate aminotransferase increased	2/1192 (0.2%)
Aspiration bronchial	1/1192 (0.1%)
Biopsy	1/1192 (0.1%)
Biopsy lung	1/1192 (0.1%)
Bleeding time prolonged	1/1192 (0.1%)
Blood sodium decreased	1/1192 (0.1%)
Bronchoscopy	1/1192 (0.1%)
Catheterisation cardiac	14/1192 (1.2%)
Catheterisation cardiac normal	1/1192 (0.1%)
Diagnostic procedure	1/1192 (0.1%)
ECG signs of myocardial ischaemia	1/1192 (0.1%)
Echocardiogram abnormal	1/1192 (0.1%)
General physical condition abnormal	1/1192 (0.1%)
Heart rate increased	1/1192 (0.1%)
Hepatic enzyme abnormal	1/1192 (0.1%)
Hepatic enzyme increased	3/1192 (0.3%)
International normalised ratio increased	6/1192 (0.5%)
Intraocular pressure increased	1/1192 (0.1%)
Investigation	2/1192 (0.2%)
Liver function test abnormal	5/1192 (0.4%)
Oxygen consumption increased	1/1192 (0.1%)
Physical examination	5/1192 (0.4%)
Pregnancy test positive	1/1192 (0.1%)
Troponin increased	1/1192 (0.1%)
Volume blood increased	1/1192 (0.1%)
White blood cell count decreased	1/1192 (0.1%)
Metabolism and nutrition disorders
Dehydration	7/1192 (0.6%)
Diabetes mellitus	1/1192 (0.1%)
Diabetes mellitus inadequate control	1/1192 (0.1%)
Electrolyte depletion	1/1192 (0.1%)
Fluid overload	10/1192 (0.8%)
Fluid retention	2/1192 (0.2%)
Gout	1/1192 (0.1%)
Hyperglycaemia	2/1192 (0.2%)
Hyperkalaemia	3/1192 (0.3%)
Hyperosmolar state	1/1192 (0.1%)
Hypokalaemia	3/1192 (0.3%)
Hyponatraemia	7/1192 (0.6%)
Hypovolaemia	1/1192 (0.1%)
Musculoskeletal and connective tissue disorders
Articular calcification	1/1192 (0.1%)
Back pain	2/1192 (0.2%)
CREST syndrome	1/1192 (0.1%)
Flank pain	1/1192 (0.1%)
Inguinal mass	1/1192 (0.1%)
Muscular weakness	1/1192 (0.1%)
Musculoskeletal chest pain	1/1192 (0.1%)
Osteitis	1/1192 (0.1%)
Osteoarthritis	1/1192 (0.1%)
Pain in extremity	1/1192 (0.1%)
Polyarthritis	1/1192 (0.1%)
Rheumatoid arthritis	1/1192 (0.1%)
Scleroderma	2/1192 (0.2%)
Systemic lupus erythematosus	2/1192 (0.2%)
Systemic sclerosis	1/1192 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/1192 (0.1%)
Brain neoplasm	1/1192 (0.1%)
Breast cancer	2/1192 (0.2%)
Breast cancer in situ	1/1192 (0.1%)
Breast cancer metastatic	2/1192 (0.2%)
Bronchial carcinoma	1/1192 (0.1%)
Chronic lymphocytic leukaemia	1/1192 (0.1%)
Colon cancer	1/1192 (0.1%)
Lipoma	1/1192 (0.1%)
Lung neoplasm malignant	4/1192 (0.3%)
Lymphoma	2/1192 (0.2%)
Metastatic neoplasm	1/1192 (0.1%)
Ovarian cancer	1/1192 (0.1%)
T-cell lymphoma recurrent	1/1192 (0.1%)
Ureteral neoplasm	1/1192 (0.1%)
Uterine cancer	2/1192 (0.2%)
Nervous system disorders
Amyotrophic lateral sclerosis	1/1192 (0.1%)
Aphasia	1/1192 (0.1%)
Cerebral haemorrhage	1/1192 (0.1%)
Cerebral hypoperfusion	1/1192 (0.1%)
Cerebrovascular accident	4/1192 (0.3%)
Convulsion	4/1192 (0.3%)
Disturbance in attention	1/1192 (0.1%)
Dizziness	3/1192 (0.3%)
Embolic stroke	1/1192 (0.1%)
Headache	4/1192 (0.3%)
Ischaemic stroke	2/1192 (0.2%)
Lethargy	1/1192 (0.1%)
Neuralgia	1/1192 (0.1%)
Neuropathy peripheral	2/1192 (0.2%)
Paraesthesia	1/1192 (0.1%)
Presyncope	4/1192 (0.3%)
Syncope	23/1192 (1.9%)
Transient ischaemic attack	5/1192 (0.4%)
Vocal cord paralysis	1/1192 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/1192 (0.1%)
Missed labour	2/1192 (0.2%)
Pregnancy	1/1192 (0.1%)
Psychiatric disorders
Acute stress disorder	1/1192 (0.1%)
Alcoholism	1/1192 (0.1%)
Bipolar disorder	1/1192 (0.1%)
Completed suicide	1/1192 (0.1%)
Confusional state	1/1192 (0.1%)
Mania	1/1192 (0.1%)
Mental status changes	1/1192 (0.1%)
Panic attack	1/1192 (0.1%)
Schizoaffective disorder	1/1192 (0.1%)
Renal and urinary disorders
Haematuria	1/1192 (0.1%)
Hydronephrosis	1/1192 (0.1%)
Nephrolithiasis	1/1192 (0.1%)
Oliguria	1/1192 (0.1%)
Proteinuria	1/1192 (0.1%)
Renal artery stenosis	1/1192 (0.1%)
Renal failure	3/1192 (0.3%)
Renal failure acute	10/1192 (0.8%)
Renal failure chronic	2/1192 (0.2%)
Ureteric haemorrhage	1/1192 (0.1%)
Reproductive system and breast disorders
Breast enlargement	1/1192 (0.1%)
Endometriosis	1/1192 (0.1%)
Menorrhagia	2/1192 (0.2%)
Ovarian cyst	1/1192 (0.1%)
Ovarian cyst ruptured	1/1192 (0.1%)
Ovarian mass	1/1192 (0.1%)
Reproductive tract disorder	1/1192 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/1192 (0.2%)
Acute respiratory failure	3/1192 (0.3%)
Asphyxia	1/1192 (0.1%)
Asthma	1/1192 (0.1%)
Atelectasis	1/1192 (0.1%)
Bronchial haemorrhage	1/1192 (0.1%)
Chronic obstructive pulmonary disease	5/1192 (0.4%)
Cough	1/1192 (0.1%)
Dyspnoea	40/1192 (3.4%)
Dyspnoea exertional	1/1192 (0.1%)
Epistaxis	1/1192 (0.1%)
Haemoptysis	18/1192 (1.5%)
Hypoxia	9/1192 (0.8%)
Lung disorder	1/1192 (0.1%)
Obstructive airways disorder	1/1192 (0.1%)
Pleural effusion	3/1192 (0.3%)
Pneumonia aspiration	1/1192 (0.1%)
Pneumonitis	1/1192 (0.1%)
Pulmonary alveolar haemorrhage	1/1192 (0.1%)
Pulmonary arterial hypertension	71/1192 (6%)
Pulmonary embolism	6/1192 (0.5%)
Pulmonary haemorrhage	2/1192 (0.2%)
Pulmonary hypertension	62/1192 (5.2%)
Pulmonary oedema	2/1192 (0.2%)
Pulmonary veno-occlusive disease	1/1192 (0.1%)
Respiratory distress	2/1192 (0.2%)
Respiratory failure	6/1192 (0.5%)
Respiratory tract haemorrhage	1/1192 (0.1%)
Skin and subcutaneous tissue disorders
Dermatosis	1/1192 (0.1%)
Surgical and medical procedures
Anticoagulant therapy	1/1192 (0.1%)
Appendicectomy	1/1192 (0.1%)
Arterial stent insertion	1/1192 (0.1%)
Atrial septal defect repair	3/1192 (0.3%)
Balloon atrial septostomy	1/1192 (0.1%)
Cardiac ablation	2/1192 (0.2%)
Cardiac operation	1/1192 (0.1%)
Cardiac pacemaker insertion	1/1192 (0.1%)
Cardioversion	2/1192 (0.2%)
Catheter placement	2/1192 (0.2%)
Central venous catheter removal	1/1192 (0.1%)
Cholecystectomy	1/1192 (0.1%)
Cholelithotomy	1/1192 (0.1%)
Colostomy closure	1/1192 (0.1%)
Coronary arterial stent insertion	1/1192 (0.1%)
Drug therapy	13/1192 (1.1%)
Endarterectomy	1/1192 (0.1%)
Endotracheal intubation	1/1192 (0.1%)
Eye operation	1/1192 (0.1%)
Foot amputation	1/1192 (0.1%)
Heart and lung transplant	3/1192 (0.3%)
Hernia diaphragmatic repair	1/1192 (0.1%)
Hospitalisation	3/1192 (0.3%)
Hysterectomy	1/1192 (0.1%)
Infusion	1/1192 (0.1%)
Inguinal hernia repair	1/1192 (0.1%)
Intraocular lens implant	1/1192 (0.1%)
Joint arthroplasty	1/1192 (0.1%)
Knee arthroplasty	1/1192 (0.1%)
Lens implant	1/1192 (0.1%)
Lung transplant	1/1192 (0.1%)
Lymphadenectomy	1/1192 (0.1%)
Office visit	3/1192 (0.3%)
Packed red blood cell transfusion	1/1192 (0.1%)
Pain management	1/1192 (0.1%)
Phlebectomy	1/1192 (0.1%)
Prophylaxis against gastrointestinal ulcer	1/1192 (0.1%)
Rehabilitation therapy	1/1192 (0.1%)
Routine health maintenance	2/1192 (0.2%)
Spinal cord operation	1/1192 (0.1%)
Spinal decompression	1/1192 (0.1%)
Surgery	3/1192 (0.3%)
Therapy cessation	1/1192 (0.1%)
Therapy regimen changed	1/1192 (0.1%)
Toe amputation	1/1192 (0.1%)
Tooth extraction	1/1192 (0.1%)
Transplant	1/1192 (0.1%)
Transurethral bladder resection	1/1192 (0.1%)
Uterine dilation and curettage	1/1192 (0.1%)
Varicose vein operation	1/1192 (0.1%)
Vascular bypass graft	1/1192 (0.1%)
Wound treatment	1/1192 (0.1%)
Vascular disorders
Circulatory collapse	1/1192 (0.1%)
Deep vein thrombosis	1/1192 (0.1%)
Haematoma	1/1192 (0.1%)
Haemorrhage	4/1192 (0.3%)
Hyperaemia	2/1192 (0.2%)
Hypertension	2/1192 (0.2%)
Hypotension	10/1192 (0.8%)
Hypovolaemic shock	1/1192 (0.1%)
Ischaemia	1/1192 (0.1%)
Peripheral ischaemia	1/1192 (0.1%)
Raynaud's phenomenon	1/1192 (0.1%)
Thrombophlebitis	2/1192 (0.2%)
Thrombosis	2/1192 (0.2%)
Other (Not Including Serious) Adverse Events
	Sitaxsentan
	Affected / at Risk (%)	# Events
Total	1069/1192 (89.7%)
Blood and lymphatic system disorders
Anaemia	77/1192 (6.5%)
Cardiac disorders
Palpitations	137/1192 (11.5%)
Gastrointestinal disorders
Abdominal pain	93/1192 (7.8%)
Abdominal pain upper	80/1192 (6.7%)
Constipation	82/1192 (6.9%)
Diarrhoea	211/1192 (17.7%)
Nausea	228/1192 (19.1%)
Vomiting	104/1192 (8.7%)
General disorders
Chest pain	201/1192 (16.9%)
Fatigue	224/1192 (18.8%)
Oedema	83/1192 (7%)
Oedema peripheral	287/1192 (24.1%)
Infections and infestations
Bronchitis	100/1192 (8.4%)
Influenza	67/1192 (5.6%)
Nasopharyngitis	219/1192 (18.4%)
Sinusitis	115/1192 (9.6%)
Upper respiratory tract infection	306/1192 (25.7%)
Urinary tract infection	115/1192 (9.6%)
Investigations
Aspartate aminotransferase increased	68/1192 (5.7%)
International normalised ratio increased	157/1192 (13.2%)
Liver function test abnormal	79/1192 (6.6%)
Metabolism and nutrition disorders
Hypokalaemia	75/1192 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	134/1192 (11.2%)
Back pain	137/1192 (11.5%)
Muscle spasms	74/1192 (6.2%)
Pain in extremity	163/1192 (13.7%)
Nervous system disorders
Dizziness	243/1192 (20.4%)
Headache	294/1192 (24.7%)
Syncope	76/1192 (6.4%)
Psychiatric disorders
Anxiety	77/1192 (6.5%)
Depression	95/1192 (8%)
Insomnia	135/1192 (11.3%)
Respiratory, thoracic and mediastinal disorders
Cough	218/1192 (18.3%)
Dyspnoea	275/1192 (23.1%)
Epistaxis	136/1192 (11.4%)
Nasal congestion	105/1192 (8.8%)
Pharyngolaryngeal pain	70/1192 (5.9%)
Pulmonary arterial hypertension	88/1192 (7.4%)
Pulmonary hypertension	75/1192 (6.3%)
Skin and subcutaneous tissue disorders
Rash	77/1192 (6.5%)

Limitations/Caveats

Mean and dispersion for clinical abnormalities were intended to be reported but due to early termination of study (09-Dec-2010) only number and percent of participants are available.

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Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.