Trial Outcomes & Findings for Combination Therapy in Pulmonary Arterial Hypertension (NCT NCT00433329)
NCT ID: NCT00433329
Last Updated: 2025-02-04
Results Overview
The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
100 participants
Primary outcome timeframe
at 16 weeks and at 28 weeks of a stepped approach to therapy
Results posted on
2025-02-04
Participant Flow
The study was conducted at 23 centers in the United States. First patient, first visit: 25 April 2007; last patient, last visit: 23 April 2010
The study included a screening phase of 2 weeks.
Participant milestones
| Measure |
Bosentan/Sildenafil
Oral bosentan 62.5 mg twice daily (BID) for 4 week followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
|
|---|---|
|
Overall Study
STARTED
|
100
|
|
Overall Study
COMPLETED
|
79
|
|
Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
Bosentan/Sildenafil
Oral bosentan 62.5 mg twice daily (BID) for 4 week followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
|
|---|---|
|
Overall Study
Adverse Event
|
9
|
|
Overall Study
Death
|
4
|
|
Overall Study
Withdrew consent
|
3
|
|
Overall Study
Discontinued sildenafil
|
2
|
|
Overall Study
Moved out of state
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Combination Therapy in Pulmonary Arterial Hypertension
Baseline characteristics by cohort
| Measure |
Bosentan/Sildenafil
n=100 Participants
Oral bosentan 62.5 mg twice daily (BID) for 4 week followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
|
|---|---|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 15.99 • n=5 Participants
|
|
Age, Customized
Between 21 and 84 years
|
100 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
82 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
100 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: at 16 weeks and at 28 weeks of a stepped approach to therapyPopulation: Intention to treat population
The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period
Outcome measures
| Measure |
Bosentan/Sildenafil
n=100 Participants
Oral bosentan 62.5 mg twice daily (BID) for 4 week followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
|
|---|---|
|
Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance ≥ 380 Meters
Week 16
|
16 participants
Interval 9.4 to 24.7
|
|
Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance ≥ 380 Meters
Week 28
|
24 participants
Interval 17.5 to 36.3
|
Adverse Events
Bosentan/Sildenafil
Serious events: 30 serious events
Other events: 88 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bosentan/Sildenafil
n=100 participants at risk
Oral bosentan 62.5 mg twice daily (BID) for 4 week followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Cardiac disorders
Bradycardia
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Cardiac disorders
Cardiac arrest
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Cardiac disorders
Cardiac failure congestive
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Cardiac disorders
Pericardial effusion
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Cardiac disorders
Right ventricular failure
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Cardiac disorders
Supraventricular tachycardia
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Chest discomfort
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Chest pain
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Death
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Generalised oedema
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Pyrexia
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Hepatobiliary disorders
Hepatic steatosis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Bronchitis
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Cellulitis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Lobar pneumonia
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Oesophageal candidiasis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Pneumonia
|
4.0%
4/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Sepsis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Septic shock
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Urinary tract infection
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Urosepsis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Nervous system disorders
Convulsion
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Nervous system disorders
Presyncope
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Nervous system disorders
Syncope
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Renal and urinary disorders
Nephrotic syndrome
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Renal and urinary disorders
Renal failure
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Renal and urinary disorders
Renal failure acute
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.0%
4/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
|
3.0%
3/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Vascular disorders
Deep vein thrombosis
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Vascular disorders
Hypotension
|
2.0%
2/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Vascular disorders
Malignant hypertension
|
1.0%
1/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
Other adverse events
| Measure |
Bosentan/Sildenafil
n=100 participants at risk
Oral bosentan 62.5 mg twice daily (BID) for 4 week followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.0%
9/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Fatigue
|
7.0%
7/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Oedema
|
5.0%
5/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
General disorders
Oedema peripheral
|
20.0%
20/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Bronchitis
|
7.0%
7/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.0%
7/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Infections and infestations
Urinary tract infection
|
6.0%
6/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Investigations
Liver function test abnormal
|
10.0%
10/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Nervous system disorders
Dizziness
|
10.0%
10/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Nervous system disorders
Headache
|
13.0%
13/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.0%
8/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.0%
15/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.0%
6/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.0%
6/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.0%
6/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
|
Vascular disorders
Hypotension
|
5.0%
5/100 • Treatment emergent adverse events (TEAEs) were collected up to 24 hours after study drug discontinuation.
|
Additional Information
Rajiv Patni/Medical Officer
Actelion Pharmaceuticals, US, Inc.
Phone: (650) 624-6900
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place