Trial Outcomes & Findings for Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (NCT NCT00319111)
NCT ID: NCT00319111
Last Updated: 2025-02-04
Results Overview
Exercise capacity was assessed using the 6MWT. Area used for testing had to be a minimum of 30m in length and 2-3m in width, with 3m gradations. Areas were well ventilated with air temperature controlled. The test was administered at the same time of day and by the same tester throughout the study. The tester measured the distance walked by non-encouraged patients during the timed 6min period. If the test was stopped before 6 minutes, the main reason for stopping the test was recorded. The tester measured the distance walked by patients during the timed 6min period.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
151 participants
Primary outcome timeframe
Until discontinuation of study drug, up to 3.3 years
Results posted on
2025-02-04
Participant Flow
Patients were enrolled at 26 centers in 13 countries (Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Italy, The Netherlands, Poland, Spain, UK, and USA. The first patient started treatment on 26 January 2006 and the last patient received their last dose of study treatment on 23 February 2009.
In total, 148 of the patients who received randomized treatment in BENEFIT (NCT00313222) rolled over into the BENEFIT OL extension. In addition, 3 patients on bosentan who were prematurely discontinued from BENEFIT (NCT00313222) were also included in the analysis, providing a total of 151 patients
Participant milestones
| Measure |
Bosentan
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Overall Study
STARTED
|
151
|
|
Overall Study
COMPLETED
|
104
|
|
Overall Study
NOT COMPLETED
|
47
|
Reasons for withdrawal
| Measure |
Bosentan
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Overall Study
Adverse Event
|
20
|
|
Overall Study
Withdrawal of consent
|
11
|
|
Overall Study
Death
|
9
|
|
Overall Study
Lack of clinical improvement
|
4
|
|
Overall Study
Administrative
|
2
|
|
Overall Study
Treatment failure
|
1
|
Baseline Characteristics
Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Baseline characteristics by cohort
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Age, Continuous
|
63.1 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
|
Age, Customized
25-81 years
|
151 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
17 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
20 participants
n=5 Participants
|
|
Region of Enrollment
France
|
18 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
14 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
3 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
2 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
|
Six-minute walk test (6MWT)
|
345.2 walk distance (m)
STANDARD_DEVIATION 93.4 • n=5 Participants
|
|
Borg dyspnea index
|
4.2 points on a scale
STANDARD_DEVIATION 2.2 • n=5 Participants
|
|
World Health Organisation (WHO) functional class
Class I
|
3 participants
n=5 Participants
|
|
World Health Organisation (WHO) functional class
Class II
|
41 participants
n=5 Participants
|
|
World Health Organisation (WHO) functional class
Class III
|
91 participants
n=5 Participants
|
|
World Health Organisation (WHO) functional class
Class IV
|
4 participants
n=5 Participants
|
|
World Health Organisation (WHO) functional class
Unassessed
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Until discontinuation of study drug, up to 3.3 yearsPopulation: Numbers of patients assessed at 6 month, month 12, month 18, month 24 and end of the treatment period were 137, 128, 121, 106, and 137 respectively
Exercise capacity was assessed using the 6MWT. Area used for testing had to be a minimum of 30m in length and 2-3m in width, with 3m gradations. Areas were well ventilated with air temperature controlled. The test was administered at the same time of day and by the same tester throughout the study. The tester measured the distance walked by non-encouraged patients during the timed 6min period. If the test was stopped before 6 minutes, the main reason for stopping the test was recorded. The tester measured the distance walked by patients during the timed 6min period.
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
month 6
|
8.4 walk distance change from baseline (m)
Standard Deviation 66.4
|
|
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
month 12
|
18.2 walk distance change from baseline (m)
Standard Deviation 64.0
|
|
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
month 24
|
20.2 walk distance change from baseline (m)
Standard Deviation 64.8
|
|
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
end of the treatment period
|
16.9 walk distance change from baseline (m)
Standard Deviation 69.4
|
|
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
month 18
|
17.7 walk distance change from baseline (m)
Standard Deviation 63.1
|
PRIMARY outcome
Timeframe: Until discontinuation of study drug, up to 3.3 yearsPopulation: Numbers of patients assessed at 6 month, month 12, month 18, month 24 and end of the treatment period were 136, 127, 120, 105, and 136 respectively
Maximal dyspnea during the walk test was assessed by the patient using the Borg dyspnea index. Immediately following each walk test, patients rated perceived maximal breathlessness during the walk test on a 12-point scale (0 \[nothing at all\], 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 \[maximum ever experienced\]).
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
month 6
|
-0.5 Scores on a scale
Standard Deviation 1.7
|
|
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
month 12
|
-0.4 Scores on a scale
Standard Deviation 1.8
|
|
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
month 18
|
-0.1 Scores on a scale
Standard Deviation 1.9
|
|
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
month 24
|
-0.1 Scores on a scale
Standard Deviation 1.9
|
|
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
end of the treatment period
|
-0.2 Scores on a scale
Standard Deviation 2.1
|
PRIMARY outcome
Timeframe: Until discontinuation of study drug, up to 3.3 yearsPopulation: Numbers of patients assessed at 6 month, month 12, month 18, month 24 and end of the treatment period were 138, 129, 123, 109, and 139 respectively
Disease severity was assessed by WHO classification of PH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
month 12
|
30 participants with improved WHO class
|
|
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
month 18
|
33 participants with improved WHO class
|
|
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
month 24
|
33 participants with improved WHO class
|
|
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
end of treatment period
|
30 participants with improved WHO class
|
|
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
month 6
|
26 participants with improved WHO class
|
PRIMARY outcome
Timeframe: Until discontinuation of study drug, up to 3.3 yearsPopulation: Study population
An event of clinical worsening was defined as death during the treatment period, a treatment-emergent adverse event that led to permanent discontinuation of study treatment and with outcome death, hospitalization due to worsening pulmonary hypertension, or lung transplantation. Patients are censored at 1 day after the end of treatment or at day of pulmonary endarterectomy if earlier.
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Time to Clinical Worsening up to End-of-study
month 18 (censored)
|
25 participants
|
|
Time to Clinical Worsening up to End-of-study
month 18 (events)
|
15 participants
|
|
Time to Clinical Worsening up to End-of-study
month 24 (censored)
|
34 participants
|
|
Time to Clinical Worsening up to End-of-study
month 30 (censored)
|
78 participants
|
|
Time to Clinical Worsening up to End-of-study
month 30 (events)
|
20 participants
|
|
Time to Clinical Worsening up to End-of-study
month 36 (censored)
|
122 participants
|
|
Time to Clinical Worsening up to End-of-study
month 36 (events)
|
21 participants
|
|
Time to Clinical Worsening up to End-of-study
end of study (censored)
|
130 participants
|
|
Time to Clinical Worsening up to End-of-study
end of study (events)
|
21 participants
|
|
Time to Clinical Worsening up to End-of-study
month 6 (censored)
|
11 participants
|
|
Time to Clinical Worsening up to End-of-study
month 6 (events)
|
8 participants
|
|
Time to Clinical Worsening up to End-of-study
month 12 (censored)
|
18 participants
|
|
Time to Clinical Worsening up to End-of-study
month 12 (events)
|
11 participants
|
|
Time to Clinical Worsening up to End-of-study
month 24 (events))
|
19 participants
|
SECONDARY outcome
Timeframe: Until discontinuation of study drug, up to 3.3 yearsPopulation: Study population
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication
|
28 participants
|
SECONDARY outcome
Timeframe: 28 days after discontinuation of study drug, up to 3.3 yearsPopulation: Study population
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Number of Patients Experiencing a Serious Adverse Event(s) up to 28 Days After Study Medication Discontinuation
|
51 participants
|
SECONDARY outcome
Timeframe: Until discontinuation of study drug, up to 3.3 yearsPopulation: study population
Number of patients with an increase in liver aminotransferases to \>3 times upper limit of normal (ULN) or a decrease in hemoglobin concentration to ≤10 g/dL
Outcome measures
| Measure |
Bosentan
n=151 Participants
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Occurrence of Liver Function Test and Hemoglobin Abnormality
Increase in liver function test
|
27 participants
|
|
Occurrence of Liver Function Test and Hemoglobin Abnormality
Decrease in hemoglobin
|
9 participants
|
Adverse Events
Bosentan
Serious events: 51 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bosentan
n=151 participants at risk
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Cardiac disorders
Right ventricular failure
|
7.3%
11/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Cardiac disorders
Cardiac failure
|
2.6%
4/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Cardiac disorders
Atrial fibrillation
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Cardiac disorders
Atrial flutter
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Cardiac disorders
Chronic right ventricular failure
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Cardiac disorders
Cor pulmonale
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Cardiac disorders
Sinoatrial block
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
3.3%
5/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.3%
2/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Chronic respiratory failure
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Investigations
Liver function test abnormal
|
3.3%
5/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Investigations
ECG signs of myocardial ischaemia
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Investigations
Heart rate abnormal
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Investigations
Hepatic enzyme increased
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Pneumonia
|
1.3%
2/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Catheter related infection
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Cellulitis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Diverticulitis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Empyema
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Lung infection
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Infections and infestations
Respiratory syncytial virus infection
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
1.3%
2/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
General disorders
Chest pain
|
1.3%
2/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
General disorders
Oedema peripheral
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
General disorders
Sudden death
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Blood and lymphatic system disorders
Anaemia
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
Abdominal wall haematoma
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
Melaena
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.3%
2/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Injury, poisoning and procedural complications
Cardiac pacemaker malfunction
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Nervous system disorders
Carotid artery stenosis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Nervous system disorders
Cerebrovascular accident
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Nervous system disorders
Diabetic hyperglycaemic coma
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Surgical and medical procedures
Alcohol detoxification
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Surgical and medical procedures
Catheterisation cardiac
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Surgical and medical procedures
Lung transplant
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Metabolism and nutrition disorders
Cachexia
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Metabolism and nutrition disorders
Diabetes mellitus insulin-dependent
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Psychiatric disorders
Abnormal behaviour
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Psychiatric disorders
Depression
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Psychiatric disorders
Mental disorder
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Renal and urinary disorders
Haematuria
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Reproductive system and breast disorders
Scrotal swelling
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Skin and subcutaneous tissue disorders
Panniculitis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Vascular disorders
Temporal arteritis
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
Other adverse events
| Measure |
Bosentan
n=151 participants at risk
Oral bosentan
* Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients
* Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight \< 40 kg)
|
|---|---|
|
Investigations
HEPATIC ENZYME INCREASED
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Investigations
LIVER FUNCTION TEST ABNORMAL
|
2.0%
3/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Metabolism and nutrition disorders
ANOREXIA
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
NASAL MUCOSAL DISORDER
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
NAUSEA
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HYPERTENSION
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
|
Gastrointestinal disorders
VOMITING
|
0.66%
1/151 • Up to 28 days after the end of study drug
Only treatment emergent adverse events that were serious or lead to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported
|
Additional Information
Loïc Perchenet PhD/Clinical Trial Leader
Actelion Pharmaceuticals Ltd
Phone: +41 61 565 6457
Results disclosure agreements
- Principal investigator is a sponsor employee Results from multi-center studies must be published or presented at congresses only in their entirety and not as individual center data, except for ancillary studies. 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