Trial Outcomes & Findings for Bosentan in Digital Ulcers (NCT NCT00319696)

NCT ID: NCT00319696

Last Updated: 2025-02-04

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 116 participants
• Primary outcome timeframe: Baseline to healing
• Results posted on: 2025-02-04

Participant Flow

Patients were enrolled at 33 centers in 7 countries (Canada, France, Germany, Italy, Switzerland, UK, and USA. The first patient enrolled and started treatment on 8 July 2004 and the last patient enrolled and started treatment on 20 October 2005.

Patients who completed RAPIDS-2 and who still had digital ulcers (DUs) or developed a new digital ulcer (DU) after the last follow-up visit were eligible. After release of the RAPIDS-2 results, patients who were prematurely discontinued from RAPIDS-2 for treatment failure or, if on placebo, for an adverse event and had DUs were also eligible.

Participant milestones

Measure	Bosentan Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter
Overall Study STARTED	116
Overall Study COMPLETED	56
Overall Study NOT COMPLETED	60

Reasons for withdrawal

Measure	Bosentan Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter
Overall Study Adverse Event	36
Overall Study withdrawal of consent	14
Overall Study administrative	7
Overall Study Lost to Follow-up	3

Baseline Characteristics

Bosentan in Digital Ulcers

Baseline characteristics by cohort

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter
Age, Continuous	49.3 years STANDARD_DEVIATION 12.0 • n=5 Participants
Age, Customized Between 24 and 79 years	116 Participants n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Region of Enrollment Canada	11 Participants n=5 Participants
Region of Enrollment France	10 Participants n=5 Participants
Region of Enrollment Germany	9 Participants n=5 Participants
Region of Enrollment Italy	9 Participants n=5 Participants
Region of Enrollment Switzerland	4 Participants n=5 Participants
Region of Enrollment United Kingdom	6 Participants n=5 Participants
Region of Enrollment United States	67 Participants n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Dressing	1.3 score on a scale STANDARD_DEVIATION 0.9 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Arising	0.5 score on a scale STANDARD_DEVIATION 0.8 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Eating	1.5 score on a scale STANDARD_DEVIATION 1.0 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Walking	0.5 score on a scale STANDARD_DEVIATION 0.7 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Hygiene	0.9 score on a scale STANDARD_DEVIATION 1.0 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Reach	1.1 score on a scale STANDARD_DEVIATION 0.9 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Grip	1.1 score on a scale STANDARD_DEVIATION 0.8 • n=5 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score Activity	1.0 score on a scale STANDARD_DEVIATION 0.9 • n=5 Participants
Overall hand pain	58.62 mm STANDARD_DEVIATION 29.80 • n=5 Participants
United Kingdom Scleroderma Functional Score (UKFS)	11.06 score on a scale STANDARD_DEVIATION 7.50 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to healing

Population: Complete healing of each baseline was not calculated due to the lack of effect on healing variables seen in the previous placebo-controlled study (RAPIDS 2). In consequence, the endpoint on time to complete healing of baseline DUs was not evaluated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: New DU occurence to healing

Population: Complete healing of each new DU was not calculated due to the lack of effect on healing variables seen in the previous placebo-controlled study (RAPIDS 2). In consequence, the endpoint on DU healing originally planned time to complete healing of new DUs was not evaluated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing change from baseline to week 16	-0.3 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing change from baseline to week 32	-0.2 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing change from baseline to week 48	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing change from baseline to week 64	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing change from baseline to week 80	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising change from baseline to week 16	0.0 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising change from baseline to week 32	-0.0 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising change from baseline to week 48	0.1 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising change from baseline to week 64	0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising change from baseline to week 80	0.1 scores on a scale Standard Deviation 0.6	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating change from baseline to week 16	-0.2 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating change from baseline to week 32	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating change from baseline to week 48	-0.2 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating change from baseline to week 64	-0.1 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating change from baseline to week 80	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking change from baseline to week 16	-0.1 scores on a scale Standard Deviation 0.6	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking change from baseline to week 32	0.0 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking change from baseline to week 48	0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking change from baseline to week 64	0.1 scores on a scale Standard Deviation 0.8	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking change from baseline to week 80	0.1 scores on a scale Standard Deviation 0.8	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene change from baseline to week 16	-0.0 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene change from baseline to week 32	-0.0 scores on a scale Standard Deviation 0.8	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene change from baseline to week 48	-0.0 scores on a scale Standard Deviation 0.8	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene change from baseline to week 64	0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene change from baseline to week 80	0.2 scores on a scale Standard Deviation 0.8	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach change from baseline to week 16	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach change from baseline to week 32	0.0 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach change from baseline to week 48	0.0 scores on a scale Standard Deviation 0.8	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach change from baseline to week 64	0.1 scores on a scale Standard Deviation 0.8	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach change from baseline to week 80	0.0 scores on a scale Standard Deviation 0.7	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip change from baseline to week 16	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip change from baseline to week 32	-0.2 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip change from baseline to week 48	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip change from baseline to week 64	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip change from baseline to week 80	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively

SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity change from baseline to week 16	-0.2 scores on a scale Standard Deviation 0.5	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity change from baseline to week 32	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity change from baseline to week 48	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity change from baseline to week 64	-0.1 scores on a scale Standard Deviation 0.7	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity change from baseline to week 80	-0.1 scores on a scale Standard Deviation 0.6	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 110, 94, 89, 81, 76, and 73, respectively

Overall hand pain related to finger ulcers was assessed by the patient using a Visual Analogue Scale. Patients were instructed to score their pain by marking on the continuous 10-cm scale, where 0 (left) was no pain and 100 (right) very severe pain, in response to the question, "How much pain have you had because of your finger ulcers in the past week?" The investigator measured the distance in millimeters between 0 and the patient mark with the ruler provided and recorded the distance.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers change from baseline to week 16	-21.59 mm Standard Deviation 28.02	—	—	—	—	—
Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers change from baseline to week 32	-28.16 mm Standard Deviation 32.64	—	—	—	—	—
Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers change from baseline to week 48	-21.90 mm Standard Deviation 32.09	—	—	—	—	—
Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers change from baseline to week 64	-22.96 mm Standard Deviation 33.27	—	—	—	—	—
Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers change from baseline to week 80	-24.29 mm Standard Deviation 36.55	—	—	—	—	—

PRIMARY outcome

Timeframe: 80 weeks

Population: number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 98, 93, 84, 82, and 78, respectively

UKFS relates to upper and lower extremity function and muscle weakness. For each item, the patient indicated the responses that best described their current ability: "able to perform in a normal manner," "able to perform with alteration in style," "can only manage with difficulty," and "impossible to achieve." Each response was given an integer from 0 (able to perform in a normal manner) to 3 (impossible to achieve), and the sum of individual responses provided an overall score of 0 to 33. Missing values were replaced with the worst value the patient reported on the other items at that visit.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) change from baseline to week 16	-1.37 score on a scale Standard Deviation 3.64	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) change from baseline to week 32	-1.25 score on a scale Standard Deviation 4.01	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) change from baseline to week 48	-0.89 score on a scale Standard Deviation 4.98	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) change from baseline to week 64	-1.17 score on a scale Standard Deviation 4.00	—	—	—	—	—
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) change from baseline to week 80	-0.45 score on a scale Standard Deviation 4.66	—	—	—	—	—

PRIMARY outcome

Timeframe: At planned visits up to week 80

Population: One patient did not have a DU at baseline (number of patients assessed at Weeks 0-4,4-8,8-16,16-24,24-32,32-40,40-48,48-56,56-64,64-72, and 72-80 were 114, 107, 103, 100, 97, 94, 88, 87, 86, 86, and 83, respectively.

The total number of new DUs per patient observed by the investigator at planned visits and new transient DUs recorded in the patient diary (a patient diary was used to record DUs that might appear and disappear between two planned visits) were assessed at each clinic visit

Outcome measures

Measure	Bosentan n=115 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer n=115 Participants Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers n=115 Participants Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers n=115 Participants Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers n=115 Participants Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers n=115 Participants Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 0-4	85 number of new digital ulcers	29 number of new digital ulcers	17 number of new digital ulcers	6 number of new digital ulcers	4 number of new digital ulcers	3 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 4-8	73 number of new digital ulcers	34 number of new digital ulcers	15 number of new digital ulcers	6 number of new digital ulcers	4 number of new digital ulcers	3 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 8-16	63 number of new digital ulcers	40 number of new digital ulcers	22 number of new digital ulcers	9 number of new digital ulcers	7 number of new digital ulcers	5 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 16-24	64 number of new digital ulcers	36 number of new digital ulcers	17 number of new digital ulcers	11 number of new digital ulcers	4 number of new digital ulcers	2 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 24-32	56 number of new digital ulcers	41 number of new digital ulcers	22 number of new digital ulcers	12 number of new digital ulcers	8 number of new digital ulcers	4 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 32-40	59 number of new digital ulcers	35 number of new digital ulcers	15 number of new digital ulcers	7 number of new digital ulcers	5 number of new digital ulcers	4 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 40-48	52 number of new digital ulcers	36 number of new digital ulcers	20 number of new digital ulcers	11 number of new digital ulcers	5 number of new digital ulcers	3 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 48-56	50 number of new digital ulcers	37 number of new digital ulcers	18 number of new digital ulcers	13 number of new digital ulcers	7 number of new digital ulcers	5 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 56-64	48 number of new digital ulcers	38 number of new digital ulcers	14 number of new digital ulcers	7 number of new digital ulcers	4 number of new digital ulcers	3 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 64-72	51 number of new digital ulcers	35 number of new digital ulcers	24 number of new digital ulcers	15 number of new digital ulcers	10 number of new digital ulcers	8 number of new digital ulcers
Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits Week 72-80	51 number of new digital ulcers	32 number of new digital ulcers	18 number of new digital ulcers	9 number of new digital ulcers	4 number of new digital ulcers	2 number of new digital ulcers

SECONDARY outcome

Timeframe: 80 weeks

Population: Study population

Number of patients with at least one treatment-emergent adverse event. All adverse events that occurred after study drug initiation and up to 24 hours after study drug discontinuation were to be recorded.

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Adverse Events up to 24 Hours After Last Study Medication	111 participants	—	—	—	—	—

SECONDARY outcome

Timeframe: 80 weeks

Population: Study population

Number of patients with an adverse event leading to permanent discontinuation of the study treatment

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Adverse Events Leading to Permanent Discontinuation of the Study Medication	36 participants	—	—	—	—	—

SECONDARY outcome

Timeframe: 80 weeks

Number of patients with at least one treatment-emergent serious adverse event (TESAE) were reported. TESAEs are serious AEs that occurred after study drug initiation and up to 28 days after study drug discontinuation. More details on the SAEs are provided in the specific Adverse Events Section

Outcome measures

Measure	Bosentan n=116 Participants Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter	At Least 1 New Ulcer Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 2 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 3 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 4 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.	At Least 5 New Ulcers Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Serious Adverse Events up to 28 Days After Last Study Medication	45 Participants	—	—	—	—	—

Adverse Events

Bosentan

Serious events: 45 serious events

Other events: 111 other events

Deaths: 6 deaths

Serious adverse events

Measure	Bosentan n=116 participants at risk Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter
Infections and infestations PNEUMONIA	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations INFECTED SKIN ULCER	3.4% 4/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations CELLULITIS	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations DEVICE RELATED INFECTION	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations SEPSIS	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations ABSCESS LIMB	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations APPENDICITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations BRONCHITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations CATHETER SITE INFECTION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations DIVERTICULITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations GANGRENE	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations GASTROENTERITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations HEPATITIS B	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations HERPES ZOSTER	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations INFLUENZA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations LOBAR PNEUMONIA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations LOCALISED INFECTION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations OSTEOMYELITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations VIRAL PERICARDITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders DYSPNOEA	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PULMONARY FIBROSIS	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PULMONARY HYPERTENSION	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PULMONARY ARTERIAL HYPERTENSION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders ABDOMINAL PAIN	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders COLITIS ISCHAEMIC	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders DIVERTICULUM INTESTINAL	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders FAECALOMA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders GASTRITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders GASTROINTESTINAL MOTILITY DISORDER	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders ILEUS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders INTESTINAL OBSTRUCTION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders NAUSEA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders OESOPHAGITIS HAEMORRHAGIC	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders VOMITING	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders SCLERODERMA	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders MYOSITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders RHEUMATOID ARTHRITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders ROTATOR CUFF SYNDROME	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders SYSTEMIC SCLEROSIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders TENOSYNOVITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
General disorders ADVERSE DRUG REACTION	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
General disorders CHEST PAIN	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
General disorders DEVICE DISLOCATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
General disorders DRUG WITHDRAWAL SYNDROME	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
General disorders IMPAIRED HEALING	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
General disorders PAIN	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
General disorders SUPRAPUBIC PAIN	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Skin and subcutaneous tissue disorders SKIN ULCER	4.3% 5/116 • 80 weeks Treatment-emergent adverse events
Skin and subcutaneous tissue disorders PYODERMA GANGRENOSUM	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Skin and subcutaneous tissue disorders SKIN DISCOLOURATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Skin and subcutaneous tissue disorders SKIN NECROSIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Vascular disorders PERIPHERAL ISCHAEMIA	3.4% 4/116 • 80 weeks Treatment-emergent adverse events
Vascular disorders EXTREMITY NECROSIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Vascular disorders FEMORAL ARTERY OCCLUSION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Vascular disorders HYPOTENSION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Cardiac disorders CARDIAC FAILURE CONGESTIVE	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Cardiac disorders ACUTE CORONARY SYNDROME	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Cardiac disorders ATRIAL FIBRILLATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Cardiac disorders CARDIAC ARREST	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Cardiac disorders MYOCARDIAL INFARCTION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Cardiac disorders MYOCARDITIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders CAROTID ARTERY STENOSIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders DIZZINESS POSTURAL	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders HYPOAESTHESIA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders LUMBAR RADICULOPATHY	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders PARAESTHESIA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Surgical and medical procedures ARTHRODESIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Surgical and medical procedures FINGER AMPUTATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Surgical and medical procedures FOOT AMPUTATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Surgical and medical procedures HIP ARTHROPLASTY	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Surgical and medical procedures LUNG TRANSPLANT	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Surgical and medical procedures REVISION OF INTERNAL FIXATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Injury, poisoning and procedural complications ASBESTOSIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Injury, poisoning and procedural complications JOINT INJURY	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Injury, poisoning and procedural complications PROCEDURAL PAIN	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Injury, poisoning and procedural complications VASCULAR GRAFT OCCLUSION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Blood and lymphatic system disorders ANAEMIA	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Renal and urinary disorders SCLERODERMA RENAL CRISIS	1.7% 2/116 • 80 weeks Treatment-emergent adverse events
Renal and urinary disorders RENAL FAILURE ACUTE	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Metabolism and nutrition disorders DEHYDRATION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Metabolism and nutrition disorders MALNUTRITION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Psychiatric disorders ALCOHOLIC PSYCHOSIS	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Psychiatric disorders DEPRESSION	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Investigations HEPATIC ENZYME INCREASED	0.86% 1/116 • 80 weeks Treatment-emergent adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CHRONIC LYMPHOCYTIC LEUKAEMIA	0.86% 1/116 • 80 weeks Treatment-emergent adverse events

Other adverse events

Measure	Bosentan n=116 participants at risk Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter
Skin and subcutaneous tissue disorders SKIN ULCER	22.4% 26/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	20.7% 24/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders ARTHRALGIA	19.0% 22/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders DIARRHOEA	18.1% 21/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations INFECTED SKIN ULCER	18.1% 21/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations LOCALISED INFECTION	14.7% 17/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders COUGH	12.9% 15/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders HEADACHE	12.1% 14/116 • 80 weeks Treatment-emergent adverse events
Skin and subcutaneous tissue disorders RASH	12.1% 14/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations NASOPHARYNGITIS	11.2% 13/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders NAUSEA	11.2% 13/116 • 80 weeks Treatment-emergent adverse events
General disorders OEDEMA PERIPHERAL	11.2% 13/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	11.2% 13/116 • 80 weeks Treatment-emergent adverse events
Skin and subcutaneous tissue disorders PRURITUS	11.2% 13/116 • 80 weeks Treatment-emergent adverse events
Investigations LIVER FUNCTION TEST ABNORMAL	10.3% 12/116 • 80 weeks Treatment-emergent adverse events
Investigations ALANINE AMINOTRANSFERASE INCREASED	9.5% 11/116 • 80 weeks Treatment-emergent adverse events
Blood and lymphatic system disorders ANAEMIA	9.5% 11/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders DYSPHAGIA	9.5% 11/116 • 80 weeks Treatment-emergent adverse events
General disorders FATIGUE	9.5% 11/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations BRONCHITIS	8.6% 10/116 • 80 weeks Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders DYSPNOEA	8.6% 10/116 • 80 weeks Treatment-emergent adverse events
Psychiatric disorders INSOMNIA	8.6% 10/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations SINUSITIS	8.6% 10/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations INFLUENZA	7.8% 9/116 • 80 weeks Treatment-emergent adverse events
General disorders PYREXIA	7.8% 9/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	6.9% 8/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders TENDONITIS	6.9% 8/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations URINARY TRACT INFECTION	6.9% 8/116 • 80 weeks Treatment-emergent adverse events
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	6.0% 7/116 • 80 weeks Treatment-emergent adverse events
Musculoskeletal and connective tissue disorders BACK PAIN	6.0% 7/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations CELLULITIS	6.0% 7/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations GASTROENTERITIS VIRAL	6.0% 7/116 • 80 weeks Treatment-emergent adverse events
General disorders ASTHENIA	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Nervous system disorders DIZZINESS	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Investigations HAEMOGLOBIN DECREASED	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Infections and infestations HERPES ZOSTER	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Gastrointestinal disorders MOUTH ULCERATION	5.2% 6/116 • 80 weeks Treatment-emergent adverse events
Investigations WEIGHT DECREASED	5.2% 6/116 • 80 weeks Treatment-emergent adverse events

Additional Information

Andjela Kusic-Pajic, MD/Clinical Project Team Leader

Actelion Pharmaceuticals Ltd

Phone: +41 61 565 64 17

Results disclosure agreements

• Principal investigator is a sponsor employee Any study-related article or abstract written independently by investigators should be submitted to Actelion for review at least 60 days prior to submission for publication or presentation.
• Publication restrictions are in place

Restriction type: OTHER