Pulmonary HypertensionPhase 3BENEFIT OLNCT00319111

Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

A Phase 3 study testing bosentan in people with Pulmonary Hypertension, run by Actelion.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The present trial investigates the long-term safety, tolerability and efficacy of bosentan in patients with inoperable CTEPH. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Pulmonary Hypertension
What is being tested?: bosentan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 151 participants
Where: No sites listed yet
Study dates: Jan 2006to Apr 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients having completed the 16-week treatment period of protocol AC-052-366 (NCT00313222)
Signed informed consent

Who cannot join

Any major violation of protocol AC-052-366 (NCT00313222)
Pregnancy or breast-feeding

About this study

Official title: Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT, NCT00313222)

The present trial investigates the long-term safety, tolerability and efficacy of bosentan in patients with inoperable CTEPH.

Conditions: Pulmonary Hypertension
Being tested: bosentan
Keywords: pulmonary hypertension, bosentan, BENEFIT, CTEPH, inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
Medical subject headings: Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

bosentanDrug
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)

Study groups in NCT00319111
Study group	Role	What they receive
Bosentan	Experimental	Open label bosentan treatment Receives: Drug: bosentan

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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]).
Measured: 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.
Measured: Until discontinuation of study drug, up to 3.3 years
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.
Measured: Until discontinuation of study drug, up to 3.3 years

Secondary outcomes (3)

Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication
Measured: 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
Measured: 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
Measured: Until discontinuation of study drug, up to 3.3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2006Apr 2009

First posted27 Apr 2006 (estimated)
Study startJan 2006
Primary completionFeb 2009
Study completionApr 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 151 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00319111
Sponsor's protocol ID: AC-052-370
Other IDs: BENEFIT OL
Acronym: BENEFIT OL
Status last verified: Jan 2025
First submitted: 26 Apr 2006
Last updated: 4 Feb 2025
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

All Pulmonary Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT, NCT00313222)
ClinicalTrials.gov ID: NCT00319111
Acronym / sponsor ID: BENEFIT OL / AC-052-370
Conditions: Pulmonary Hypertension
Keywords: pulmonary hypertension, bosentan, BENEFIT, CTEPH, inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 151 participants (actual)
Lead sponsor: ActelionIndustry (pharma, biotech, devices)
Study start: Jan 2006
Primary completion: Feb 2009 (actual)
Study completion: Apr 2009 (actual)
First posted: 27 Apr 2006 (estimated)
Results: Posted 31 Dec 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The present trial investigates the long-term safety, tolerability and efficacy of bosentan in patients with inoperable CTEPH.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Bosentan	Experimental	Drug: bosentanOpen label bosentan treatment

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patients having completed the 16-week treatment period of protocol AC-052-366 (NCT00313222)
Signed informed consent

Key exclusion criteria (2 listed)

Any major violation of protocol AC-052-366 (NCT00313222)
Pregnancy or breast-feeding

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
bosentanOral 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)	Drug	Bosentan

Primary outcome

Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
Time frame: Until discontinuation of study drug, up to 3.3 years
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.
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
Time frame: Until discontinuation of study drug, up to 3.3 years
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]).
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
Time frame: Until discontinuation of study drug, up to 3.3 years
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.
Time to Clinical Worsening up to End-of-study
Time frame: Until discontinuation of study drug, up to 3.3 years
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.

3 secondary outcomes

Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication
Time frame: 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
Time frame: 28 days after discontinuation of study drug, up to 3.3 years
Occurrence of Liver Function Test and Hemoglobin Abnormality
Time frame: Until discontinuation of study drug, up to 3.3 years

Results and safety

Results posted to the registry on 31 Dec 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bosentan	151	104

Primary outcome: Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance

Time frame: Until discontinuation of study drug, up to 3.3 years. Mean (Standard Deviation). Unit: walk distance change from baseline (m)

Measure	Bosentan n = 151
month 6	8.4 (66.4)
month 12	18.2 (64.0)
month 18	17.7 (63.1)
month 24	20.2 (64.8)
end of the treatment period	16.9 (69.4)

Population analysed: 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

Primary outcome: Change From Baseline to All Assessed Time Points in Borg Dyspnea Index

Time frame: Until discontinuation of study drug, up to 3.3 years. Mean (Standard Deviation). Unit: Scores on a scale

Measure	Bosentan n = 151
month 6	-0.5 (1.7)
month 12	-0.4 (1.8)
month 18	-0.1 (1.9)
month 24	-0.1 (1.9)
end of the treatment period	-0.2 (2.1)

Population analysed: 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

Primary outcome: Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)

Time frame: Until discontinuation of study drug, up to 3.3 years. Number. Unit: participants with improved WHO class

Measure	Bosentan n = 151
month 6	26
month 12	30
month 18	33
month 24	33
end of treatment period	30

Population analysed: 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

Primary outcome: Time to Clinical Worsening up to End-of-study

Time frame: Until discontinuation of study drug, up to 3.3 years. Number. Unit: participants

Measure	Bosentan n = 151
month 6 (censored)	11
month 6 (events)	8
month 12 (censored)	18
month 12 (events)	11
month 18 (censored)	25
month 18 (events)	15
month 24 (censored)	34
month 24 (events))	19

Population analysed: Study population

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 28 days after the end of study drug. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bosentan	51 of 151 (33.8%)	11 of 151 (7.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Pulmonary Hypertension

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing bosentan in people with Pulmonary Hypertension, run by Actelion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance (time frame: Until discontinuation of study drug, up to 3.3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00319111.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.