Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| BENEFIT OL |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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The present trial investigates the long-term safety, tolerability and efficacy of bosentan in patients with inoperable CTEPH.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bosentan | Experimental | Open label bosentan treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bosentan | Drug | Oral bosentan
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance | 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. | Until discontinuation of study drug, up to 3.3 years |
| Change From Baseline to All Assessed Time Points in Borg Dyspnea Index | 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]). | Until discontinuation of study drug, up to 3.3 years |
| Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH) | 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. | Until discontinuation of study drug, up to 3.3 years |
| Time to Clinical Worsening up to End-of-study |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication | Until discontinuation of study drug, up to 3.3 years | |
| Number of Patients Experiencing a Serious Adverse Event(s) up to 28 Days After Study Medication Discontinuation |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
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
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Bosentan | Oral bosentan
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Bosentan | Oral bosentan
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance | 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. | 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 | Posted | Mean | Standard Deviation | walk distance change from baseline (m) | Until discontinuation of study drug, up to 3.3 years |
|
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
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bosentan | Oral bosentan
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right ventricular failure | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HEPATIC ENZYME INCREASED | Investigations | MedDRA (10.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Loïc Perchenet PhD/Clinical Trial Leader | Actelion Pharmaceuticals Ltd | +41 61 565 6457 |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077300 | Bosentan |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
Not provided
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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.
| Until discontinuation of study drug, up to 3.3 years |
| 28 days after discontinuation of study drug, up to 3.3 years |
| Occurrence of Liver Function Test and Hemoglobin Abnormality | 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 | Until discontinuation of study drug, up to 3.3 years |
| Lack of clinical improvement |
|
| Administrative |
|
| Treatment failure |
|
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Six-minute walk test (6MWT) | Exercise capacity was determined for 137 of the 151 participants using the 6MWT. Area used for testing was 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. | Mean | Standard Deviation | walk distance (m) |
|
| Borg dyspnea index | The Borg dyspnea index was assessed in 136 out of the 151 participants. 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]). | Mean | Standard Deviation | points on a scale |
|
| World Health Organisation (WHO) functional class | Disease severity assessed using WHO classification of pulmonary hypertension: Class I: no limitation of physical activity etc. Class II: slight limitation of physical activity etc. Class III: marked limitation of physical activity etc. Class IV: inability to carry out physical activity without symptoms. Signs of right heart failure etc. WHO functional class was assessed in 139 patients | Number | participants |
|
Oral bosentan
|
|
|
| Primary | Change From Baseline to All Assessed Time Points in Borg Dyspnea Index | 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]). | 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 | Posted | Mean | Standard Deviation | Scores on a scale | Until discontinuation of study drug, up to 3.3 years |
|
|
|
| Primary | Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH) | 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. | 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 | Posted | Number | participants with improved WHO class | Until discontinuation of study drug, up to 3.3 years |
|
|
|
| Primary | Time to Clinical Worsening up to End-of-study | 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. | Study population | Posted | Number | participants | Until discontinuation of study drug, up to 3.3 years |
|
|
|
| Secondary | Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication | Study population | Posted | Number | participants | Until discontinuation of study drug, up to 3.3 years |
|
|
|
| Secondary | Number of Patients Experiencing a Serious Adverse Event(s) up to 28 Days After Study Medication Discontinuation | Study population | Posted | Number | participants | 28 days after discontinuation of study drug, up to 3.3 years |
|
|
|
| Secondary | Occurrence of Liver Function Test and Hemoglobin Abnormality | 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 | study population | Posted | Number | participants | Until discontinuation of study drug, up to 3.3 years |
|
|
|
| 51 |
| 151 |
| 11 |
| 151 |
| Cardiac failure | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Atrial flutter | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Chronic right ventricular failure | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Cor pulmonale | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Sinoatrial block | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pulmonary arterial hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| ECG signs of myocardial ischaemia | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Heart rate abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Catheter related infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Empyema | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Abdominal wall haematoma | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Intestinal haemorrhage | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
|
| Cardiac pacemaker malfunction | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
|
| Carotid artery stenosis | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Diabetic hyperglycaemic coma | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Alcohol detoxification | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
|
| Catheterisation cardiac | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
|
| Lung transplant | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Diabetes mellitus insulin-dependent | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Fluid overload | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Abnormal behaviour | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Mental disorder | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Scrotal swelling | Reproductive system and breast disorders | MedDRA (10.0) | Systematic Assessment |
|
| Panniculitis | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Temporal arteritis | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| LIVER FUNCTION TEST ABNORMAL | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| ANOREXIA | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| DYSPEPSIA | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| NASAL MUCOSAL DISORDER | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| PULMONARY HYPERTENSION | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
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.
| D002318 |
| Cardiovascular Diseases |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Title | Measurements |
|---|---|
|
| month 24 |
|
| end of the treatment period |
|
| Title | Measurements |
|---|
|
| month 24 |
|
| end of treatment period |
|
| Title | Measurements |
|---|---|
|
| month 12 (events) |
|
| month 18 (censored) |
|
| month 18 (events) |
|
| month 24 (censored) |
|
| month 24 (events)) |
|
| month 30 (censored) |
|
| month 30 (events) |
|
| month 36 (censored) |
|
| month 36 (events) |
|
| end of study (censored) |
|
| end of study (events) |
|