Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bosentan in Digital Ulcers (RAPIDS 2 OL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00319696
Recruitment Status : Completed
First Posted : April 27, 2006
Results First Posted : August 8, 2012
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Digital Ulcers
Interventions Drug: Bosentan 62.5 mg
Drug: Bosentan 125 mg
Enrollment 116
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Bosentan
Hide Arm/Group Description 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
Period Title: Overall Study
Started 116
Completed 56
Not Completed 60
Reason Not Completed
Adverse Event             36
withdrawal of consent             14
administrative             7
Lost to Follow-up             3
Arm/Group Title Bosentan
Hide Arm/Group Description 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 Number of Baseline Participants 116
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 116 participants
49.3  (12.0)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Between 24 and 79 years Number Analyzed 116 participants
116
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants
Female
87
  75.0%
Male
29
  25.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants
Canada
11
   9.5%
France
10
   8.6%
Germany
9
   7.8%
Italy
9
   7.8%
Switzerland
4
   3.4%
United Kingdom
6
   5.2%
United States
67
  57.8%
Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 116 participants
Dressing 1.3  (0.9)
Arising 0.5  (0.8)
Eating 1.5  (1.0)
Walking 0.5  (0.7)
Hygiene 0.9  (1.0)
Reach 1.1  (0.9)
Grip 1.1  (0.8)
Activity 1.0  (0.9)
[1]
Measure Description: 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.
Overall hand pain   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 116 participants
58.62  (29.80)
[1]
Measure Description: 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.
United Kingdom Scleroderma Functional Score (UKFS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 116 participants
11.06  (7.50)
[1]
Measure Description: 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.
1.Primary Outcome
Title Time to Complete Healing of Each Baseline DU
Hide Description [Not Specified]
Time Frame Baseline to healing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Time to Complete Healing of Each New DU
Hide Description [Not Specified]
Time Frame New DU occurence to healing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.3  (0.6)
change from baseline to week 32 -0.2  (0.7)
change from baseline to week 48 -0.1  (0.7)
change from baseline to week 64 -0.1  (0.7)
change from baseline to week 80 -0.1  (0.7)
4.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 0.0  (0.6)
change from baseline to week 32 -0.0  (0.6)
change from baseline to week 48 0.1  (0.6)
change from baseline to week 64 0.1  (0.7)
change from baseline to week 80 0.1  (0.6)
5.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.2  (0.6)
change from baseline to week 32 -0.1  (0.7)
change from baseline to week 48 -0.2  (0.7)
change from baseline to week 64 -0.1  (0.6)
change from baseline to week 80 -0.1  (0.7)
6.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.1  (0.6)
change from baseline to week 32 0.0  (0.7)
change from baseline to week 48 0.1  (0.7)
change from baseline to week 64 0.1  (0.8)
change from baseline to week 80 0.1  (0.8)
7.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.0  (0.7)
change from baseline to week 32 -0.0  (0.8)
change from baseline to week 48 -0.0  (0.8)
change from baseline to week 64 0.1  (0.7)
change from baseline to week 80 0.2  (0.8)
8.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.1  (0.7)
change from baseline to week 32 0.0  (0.7)
change from baseline to week 48 0.0  (0.8)
change from baseline to week 64 0.1  (0.8)
change from baseline to week 80 0.0  (0.7)
9.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.1  (0.7)
change from baseline to week 32 -0.2  (0.7)
change from baseline to week 48 -0.1  (0.7)
change from baseline to week 64 -0.1  (0.7)
change from baseline to week 80 -0.1  (0.7)
10.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: scores on a scale
change from baseline to week 16 -0.2  (0.5)
change from baseline to week 32 -0.1  (0.7)
change from baseline to week 48 -0.1  (0.7)
change from baseline to week 64 -0.1  (0.7)
change from baseline to week 80 -0.1  (0.6)
11.Primary Outcome
Title Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: mm
change from baseline to week 16 -21.59  (28.02)
change from baseline to week 32 -28.16  (32.64)
change from baseline to week 48 -21.90  (32.09)
change from baseline to week 64 -22.96  (33.27)
change from baseline to week 80 -24.29  (36.55)
12.Primary Outcome
Title Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS)
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Mean (Standard Deviation)
Unit of Measure: score on a scale
change from baseline to week 16 -1.37  (3.64)
change from baseline to week 32 -1.25  (4.01)
change from baseline to week 48 -0.89  (4.98)
change from baseline to week 64 -1.17  (4.00)
change from baseline to week 80 -0.45  (4.66)
13.Primary Outcome
Title Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits
Hide Description 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
Time Frame At planned visits up to week 80
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0 New Ulcers At Least 1 New Ulcer At Least 2 New Ulcers At Least 3 New Ulcers At Least 4 New Ulcers At Least 5 New Ulcers
Hide Arm/Group Description:
Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Number of new DUs includes the new number at each visit and the transient ulcers between visits.
Overall Number of Participants Analyzed 115 115 115 115 115 115
Measure Type: Number
Unit of Measure: number of new digital ulcers
Week 0-4 85 29 17 6 4 3
Week 4-8 73 34 15 6 4 3
Week 8-16 63 40 22 9 7 5
Week 16-24 64 36 17 11 4 2
Week 24-32 56 41 22 12 8 4
Week 32-40 59 35 15 7 5 4
Week 40-48 52 36 20 11 5 3
Week 48-56 50 37 18 13 7 5
Week 56-64 48 38 14 7 4 3
Week 64-72 51 35 24 15 10 8
Week 72-80 51 32 18 9 4 2
14.Secondary Outcome
Title Adverse Events up to 24 Hours After Last Study Medication
Hide Description 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.
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Study population
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Measure Type: Number
Unit of Measure: participants
111
15.Secondary Outcome
Title Adverse Events Leading to Permanent Discontinuation of the Study Medication
Hide Description Number of patients with an adverse event leading to permanent discontinuation of the study treatment
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Study population
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Measure Type: Number
Unit of Measure: participants
36
16.Secondary Outcome
Title Serious Adverse Events up to 28 Days After Last Study Medication
Hide Description 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
Time Frame 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bosentan
Hide Arm/Group Description:
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 Number of Participants Analyzed 116
Measure Type: Number
Unit of Measure: Participants
45
Time Frame 80 weeks
Adverse Event Reporting Description Treatment-emergent adverse events
 
Arm/Group Title Bosentan
Hide Arm/Group Description 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
All-Cause Mortality
Bosentan
Affected / at Risk (%)
Total   6/116 (5.17%) 
Hide Serious Adverse Events
Bosentan
Affected / at Risk (%)
Total   45/116 (38.79%) 
Blood and lymphatic system disorders   
ANAEMIA  1  2/116 (1.72%) 
IRON DEFICIENCY ANAEMIA  1  1/116 (0.86%) 
Cardiac disorders   
CARDIAC FAILURE CONGESTIVE  1  2/116 (1.72%) 
ACUTE CORONARY SYNDROME  1  1/116 (0.86%) 
ATRIAL FIBRILLATION  1  1/116 (0.86%) 
CARDIAC ARREST  1  1/116 (0.86%) 
MYOCARDIAL INFARCTION  1  1/116 (0.86%) 
MYOCARDITIS  1  1/116 (0.86%) 
Gastrointestinal disorders   
ABDOMINAL PAIN  1  2/116 (1.72%) 
ABDOMINAL PAIN LOWER  1  1/116 (0.86%) 
COLITIS ISCHAEMIC  1  1/116 (0.86%) 
DIVERTICULUM INTESTINAL  1  1/116 (0.86%) 
FAECALOMA  1  1/116 (0.86%) 
GASTRITIS  1  1/116 (0.86%) 
GASTROINTESTINAL MOTILITY DISORDER  1  1/116 (0.86%) 
ILEUS  1  1/116 (0.86%) 
INTESTINAL OBSTRUCTION  1  1/116 (0.86%) 
NAUSEA  1  1/116 (0.86%) 
OESOPHAGITIS HAEMORRHAGIC  1  1/116 (0.86%) 
VOMITING  1  1/116 (0.86%) 
General disorders   
ADVERSE DRUG REACTION  1  2/116 (1.72%) 
CHEST PAIN  1  2/116 (1.72%) 
DEVICE DISLOCATION  1  1/116 (0.86%) 
DRUG WITHDRAWAL SYNDROME  1  1/116 (0.86%) 
IMPAIRED HEALING  1  1/116 (0.86%) 
PAIN  1  1/116 (0.86%) 
SUPRAPUBIC PAIN  1  1/116 (0.86%) 
Infections and infestations   
PNEUMONIA  1  6/116 (5.17%) 
INFECTED SKIN ULCER  1  4/116 (3.45%) 
CELLULITIS  1  2/116 (1.72%) 
DEVICE RELATED INFECTION  1  2/116 (1.72%) 
SEPSIS  1  2/116 (1.72%) 
ABSCESS LIMB  1  1/116 (0.86%) 
APPENDICITIS  1  1/116 (0.86%) 
BRONCHITIS  1  1/116 (0.86%) 
CATHETER SITE INFECTION  1  1/116 (0.86%) 
DIVERTICULITIS  1  1/116 (0.86%) 
GANGRENE  1  1/116 (0.86%) 
GASTROENTERITIS  1  1/116 (0.86%) 
HEPATITIS B  1  1/116 (0.86%) 
HERPES ZOSTER  1  1/116 (0.86%) 
INFLUENZA  1  1/116 (0.86%) 
LOBAR PNEUMONIA  1  1/116 (0.86%) 
LOCALISED INFECTION  1  1/116 (0.86%) 
OSTEOMYELITIS  1  1/116 (0.86%) 
VIRAL PERICARDITIS  1  1/116 (0.86%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  1/116 (0.86%) 
Injury, poisoning and procedural complications   
ASBESTOSIS  1  1/116 (0.86%) 
JOINT INJURY  1  1/116 (0.86%) 
PROCEDURAL PAIN  1  1/116 (0.86%) 
VASCULAR GRAFT OCCLUSION  1  1/116 (0.86%) 
Investigations   
HEPATIC ENZYME INCREASED  1  1/116 (0.86%) 
Metabolism and nutrition disorders   
DEHYDRATION  1  1/116 (0.86%) 
MALNUTRITION  1  1/116 (0.86%) 
Musculoskeletal and connective tissue disorders   
INTERVERTEBRAL DISC PROTRUSION  1  2/116 (1.72%) 
SCLERODERMA  1  2/116 (1.72%) 
MUSCULAR WEAKNESS  1  1/116 (0.86%) 
MYOSITIS  1  1/116 (0.86%) 
OSTEOARTHRITIS  1  1/116 (0.86%) 
PAIN IN EXTREMITY  1  1/116 (0.86%) 
RHEUMATOID ARTHRITIS  1  1/116 (0.86%) 
ROTATOR CUFF SYNDROME  1  1/116 (0.86%) 
SYSTEMIC SCLEROSIS  1  1/116 (0.86%) 
TENOSYNOVITIS  1  1/116 (0.86%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
CHRONIC LYMPHOCYTIC LEUKAEMIA  1  1/116 (0.86%) 
Nervous system disorders   
CAROTID ARTERY STENOSIS  1  1/116 (0.86%) 
CEREBROVASCULAR ACCIDENT  1  1/116 (0.86%) 
DIZZINESS POSTURAL  1  1/116 (0.86%) 
HYPOAESTHESIA  1  1/116 (0.86%) 
LUMBAR RADICULOPATHY  1  1/116 (0.86%) 
PARAESTHESIA  1  1/116 (0.86%) 
Psychiatric disorders   
ALCOHOLIC PSYCHOSIS  1  1/116 (0.86%) 
DEPRESSION  1  1/116 (0.86%) 
Renal and urinary disorders   
SCLERODERMA RENAL CRISIS  1  2/116 (1.72%) 
RENAL FAILURE ACUTE  1  1/116 (0.86%) 
Respiratory, thoracic and mediastinal disorders   
DYSPNOEA  1  6/116 (5.17%) 
PULMONARY FIBROSIS  1  2/116 (1.72%) 
PULMONARY HYPERTENSION  1  2/116 (1.72%) 
ACUTE RESPIRATORY FAILURE  1  1/116 (0.86%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  1/116 (0.86%) 
PLEURAL EFFUSION  1  1/116 (0.86%) 
PNEUMONITIS  1  1/116 (0.86%) 
PNEUMOTHORAX  1  1/116 (0.86%) 
PULMONARY ARTERIAL HYPERTENSION  1  1/116 (0.86%) 
Skin and subcutaneous tissue disorders   
SKIN ULCER  1  5/116 (4.31%) 
PYODERMA GANGRENOSUM  1  1/116 (0.86%) 
SKIN DISCOLOURATION  1  1/116 (0.86%) 
SKIN NECROSIS  1  1/116 (0.86%) 
Surgical and medical procedures   
ARTHRODESIS  1  1/116 (0.86%) 
FINGER AMPUTATION  1  1/116 (0.86%) 
FOOT AMPUTATION  1  1/116 (0.86%) 
HIP ARTHROPLASTY  1  1/116 (0.86%) 
LUNG TRANSPLANT  1  1/116 (0.86%) 
REVISION OF INTERNAL FIXATION  1  1/116 (0.86%) 
Vascular disorders   
PERIPHERAL ISCHAEMIA  1  4/116 (3.45%) 
EXTREMITY NECROSIS  1  1/116 (0.86%) 
FEMORAL ARTERY OCCLUSION  1  1/116 (0.86%) 
HYPOTENSION  1  1/116 (0.86%) 
1
Term from vocabulary, MedDRA (13.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bosentan
Affected / at Risk (%)
Total   111/116 (95.69%) 
Blood and lymphatic system disorders   
ANAEMIA  1  11/116 (9.48%) 
Gastrointestinal disorders   
DIARRHOEA  1  21/116 (18.10%) 
NAUSEA  1  13/116 (11.21%) 
DYSPHAGIA  1  11/116 (9.48%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  8/116 (6.90%) 
MOUTH ULCERATION  1  6/116 (5.17%) 
General disorders   
OEDEMA PERIPHERAL  1  13/116 (11.21%) 
FATIGUE  1  11/116 (9.48%) 
PYREXIA  1  9/116 (7.76%) 
ASTHENIA  1  6/116 (5.17%) 
Infections and infestations   
UPPER RESPIRATORY TRACT INFECTION  1  24/116 (20.69%) 
INFECTED SKIN ULCER  1  21/116 (18.10%) 
LOCALISED INFECTION  1  17/116 (14.66%) 
NASOPHARYNGITIS  1  13/116 (11.21%) 
BRONCHITIS  1  10/116 (8.62%) 
SINUSITIS  1  10/116 (8.62%) 
INFLUENZA  1  9/116 (7.76%) 
URINARY TRACT INFECTION  1  8/116 (6.90%) 
CELLULITIS  1  7/116 (6.03%) 
GASTROENTERITIS VIRAL  1  7/116 (6.03%) 
HERPES ZOSTER  1  6/116 (5.17%) 
Investigations   
LIVER FUNCTION TEST ABNORMAL  1  12/116 (10.34%) 
ALANINE AMINOTRANSFERASE INCREASED  1  11/116 (9.48%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  7/116 (6.03%) 
HAEMOGLOBIN DECREASED  1  6/116 (5.17%) 
WEIGHT DECREASED  1  6/116 (5.17%) 
Musculoskeletal and connective tissue disorders   
ARTHRALGIA  1  22/116 (18.97%) 
PAIN IN EXTREMITY  1  13/116 (11.21%) 
TENDONITIS  1  8/116 (6.90%) 
BACK PAIN  1  7/116 (6.03%) 
Nervous system disorders   
HEADACHE  1  14/116 (12.07%) 
DIZZINESS  1  6/116 (5.17%) 
Psychiatric disorders   
INSOMNIA  1  10/116 (8.62%) 
Respiratory, thoracic and mediastinal disorders   
COUGH  1  15/116 (12.93%) 
DYSPNOEA  1  10/116 (8.62%) 
Skin and subcutaneous tissue disorders   
SKIN ULCER  1  26/116 (22.41%) 
RASH  1  14/116 (12.07%) 
PRURITUS  1  13/116 (11.21%) 
1
Term from vocabulary, MedDRA (13.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Andjela Kusic-Pajic, MD/Clinical Project Team Leader
Organization: Actelion Pharmaceuticals Ltd
Phone: +41 61 565 64 17
Layout table for additonal information
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00319696    
Other Study ID Numbers: AC-052-333
First Submitted: April 27, 2006
First Posted: April 27, 2006
Results First Submitted: June 29, 2012
Results First Posted: August 8, 2012
Last Update Posted: January 8, 2019