Pulmonary HypertensionPhase 4NCT00679068
Effects of Bosentan on Respiratory Mechanics
A Phase 4 study testing Bosentan in people with Pulmonary Hypertension, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
Trial summary
Bosentan has been largely used in the treatment of pulmonary hypertension (PH). It can improve exercise capacity, lower Borg dyspnoea score nad these effects are usually associated with the concomitant improvement in cardiopulmonary haemodynamics. 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteItaly
- Study dates
- May 2008to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Adult patients with World Health Organization (WHO) functional class II-III.
- A systemic pulse oximetry (SpO2) between 70% and 90% at rest with room air and a baseline 6-minute walk distance between 150 and 450 m were required for inclusion.
- PAH confirmed by cardiac catheterization as mean pulmonary arterial pressure greater or equal to25 mm Hg, pulmonary capillary wedge pressure lower 15 mm Hg,
Who cannot join
- Patients were excluded if they had patent ductus arteriosus (for hemodynamic assessment difficulties)
- complex congenital heart defect
- left ventricular dysfunction (left ventricular ejection fraction lower 40%)
- restrictive lung disease (total lung capacity lower 70% predicted)
- obstructive lung disease (forced expiratory volume in 1 second [FEV1] lower 70% predicted
- with FEV1/forced vital capacity lower 60%)
- or previously diagnosed coronary artery disease.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of 12 Weeks Treatment With Bosentan on Respiratory Mechanics in Patients With Pulmonary Hypertension
Bosentan has been largely used in the treatment of pulmonary hypertension (PH). It can improve exercise capacity, lower Borg dyspnoea score nad these effects are usually associated with the concomitant improvement in cardiopulmonary haemodynamics.
No physiological study has so far verified the hypothesis that Bosentan may laso have an effect on the "respiratory side" of the cadio-pulmonary system (i.e. on pulmonary mechanics and work of breathing)
Read the detailed description
Endothelins are powerful vasoconstrictor peptides that also play numerous other functions in many different organs. Endothelin-1 (ET-1) is the most abundant and important of this family of peptides in blood vessels. Production of ET-1 is increased in the endothelium and the kidney in salt-dependent models of hypertension ET-1 elicits an inflammatory response by increasing oxidant stress in the vascular wall, which induces vascular remodeling and endothelial dysfunction found in the hypertensive models that exhibit an endothelin-mediated component. Endothelin receptor antagonists lower blood pressure in hypertensive patients. They could become therapeutic agents for prevention of target organ damage in hypertension and in type 2 diabetes, chronic renal failure and congestive heart failure. Side effects of endothelin receptor blockers have prevented up to the present their development for these indications. Endothelin antagonists have been approved only for the treatment of pulmonary hypertension, a rapidly fatal condition in which the endothelin system plays an important role and endothelin antagonists exert favorable effects.The exact mechanism of action of ERAs on the pulmonary vascular bed remains unclear. Vasodilatation is just a part of the mechanism, since usually 70%-80% of Idiopathic PAH patients do not respond acutely to vasodilators. Endothelin is likely to be involved in pulmonary vasoconstriction, inflammation, cellular proliferation and fibrosis ie. remodelling Recent research illustrates that bosentan is capable of blunting the vascular remodelling normally associated with PAH If ERAs could prevent remodelling, they might substantially improve the long-term survival in patients with mild symptoms (WHO class II or I).
Bosentan, the most popular endothelin receptor antagonist, has been largely used in the treatment of pulmonary hypertension (PH). It can improve exercise capacity, lower Borg dyspnoea score nad these effects are usually associated with the concomitant improvement in cardiopulmonary haemodynamics.
No physiological study has so far verified the hypothesis that Bosentan may laso have an effect on the "respiratory side" of the cadio-pulmonary system (i.e. on pulmonary mechanics and work of breathing)
- Conditions
- Pulmonary Hypertension
- Being tested
- Bosentan
- Keywords
- respiratory mechanics, bosentan, exercise capacity
- 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
62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.for the remaining 8 weeks (if tolerated)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | treatment with Bosentan Receives: Drug: Bosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory mechanics (i.e. lung compliance, resistances and work of breathing)
Measured: 12 weeks
Secondary outcomes (1)
exercise capacity (i.e. 6 mwd), dyspnea, oxygen saturation and cardiac function (i.e. hemodynamic evaluation)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2008 (estimated)
- Study startMay 2008
- Primary completionDec 2012
- Study completionJun 2013
Why it stopped: lack of recruitment of patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- 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 4
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr. Stefano Nava, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Investigators
- Stefano Nava, Principal investigator, Fondazione S.Maugeri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00679068
- Sponsor's protocol ID
- 525FSM
- Status last verified
- Aug 2015
- First submitted
- 14 May 2008
- Last updated
- 20 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of 12 Weeks Treatment With Bosentan on Respiratory Mechanics in Patients With Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT00679068
- Acronym / sponsor ID
- 525FSM
- Conditions
- Pulmonary Hypertension
- Keywords
- respiratory mechanics, bosentan, exercise capacity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of recruitment of patients
- Enrolment
- 4 participants (actual)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 16 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bosentan has been largely used in the treatment of pulmonary hypertension (PH). It can improve exercise capacity, lower Borg dyspnoea score nad these effects are usually associated with the concomitant improvement in cardiopulmonary haemodynamics.
No physiological study has so far verified the hypothesis that Bosentan may laso have an effect on the "respiratory side" of the cadio-pulmonary system (i.e. on pulmonary mechanics and work of breathing)
Detailed description
Endothelins are powerful vasoconstrictor peptides that also play numerous other functions in many different organs. Endothelin-1 (ET-1) is the most abundant and important of this family of peptides in blood vessels. Production of ET-1 is increased in the endothelium and the kidney in salt-dependent models of hypertension ET-1 elicits an inflammatory response by increasing oxidant stress in the vascular wall, which induces vascular remodeling and endothelial dysfunction found in the hypertensive models that exhibit an endothelin-mediated component. Endothelin receptor antagonists lower blood pressure in hypertensive patients. They could become therapeutic agents for prevention of target organ damage in hypertension and in type 2 diabetes, chronic renal failure and congestive heart failure. Side effects of endothelin receptor blockers have prevented up to the present their development for these indications. Endothelin antagonists have been approved only for the treatment of pulmonary hypertension, a rapidly fatal condition in which the endothelin system plays an important role and endothelin antagonists exert favorable effects.The exact mechanism of action of ERAs on the pulmonary vascular bed remains unclear. Vasodilatation is just a part of the mechanism, since usually 70%-80% of Idiopathic PAH patients do not respond acutely to vasodilators. Endothelin is likely to be involved in pulmonary vasoconstriction, inflammation, cellular proliferation and fibrosis ie. remodelling Recent research illustrates that bosentan is capable of blunting the vascular remodelling normally associated with PAH If ERAs could prevent remodelling, they might substantially improve the long-term survival in patients with mild symptoms (WHO class II or I).
Bosentan, the most popular endothelin receptor antagonist, has been largely used in the treatment of pulmonary hypertension (PH). It can improve exercise capacity, lower Borg dyspnoea score nad these effects are usually associated with the concomitant improvement in cardiopulmonary haemodynamics.
No physiological study has so far verified the hypothesis that Bosentan may laso have an effect on the "respiratory side" of the cadio-pulmonary system (i.e. on pulmonary mechanics and work of breathing)
Study design
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Bosentantreatment with Bosentan |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult patients with World Health Organization (WHO) functional class II-III.
- A systemic pulse oximetry (SpO2) between 70% and 90% at rest with room air and a baseline 6-minute walk distance between 150 and 450 m were required for inclusion.
- PAH confirmed by cardiac catheterization as mean pulmonary arterial pressure greater or equal to25 mm Hg, pulmonary capillary wedge pressure lower 15 mm Hg,
Key exclusion criteria (7 listed)
- Patients were excluded if they had patent ductus arteriosus (for hemodynamic assessment difficulties)
- complex congenital heart defect
- left ventricular dysfunction (left ventricular ejection fraction lower 40%)
- restrictive lung disease (total lung capacity lower 70% predicted)
- obstructive lung disease (forced expiratory volume in 1 second [FEV1] lower 70% predicted
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 |
|---|---|---|
| Bosentan62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.for the remaining 8 weeks (if tolerated) | Drug | 1 |
Primary outcome
Respiratory mechanics (i.e. lung compliance, resistances and work of breathing)
Time frame: 12 weeks
1 secondary outcome
exercise capacity (i.e. 6 mwd), dyspnea, oxygen saturation and cardiac function (i.e. hemodynamic evaluation)
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: lack of recruitment of patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2015.
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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.
Stefano Nava principal investigator
Fondazione S.Maugeri
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bosentan in people with Pulmonary Hypertension, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
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 3 inclusion and 7 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: stopped early, as of the sponsor's last update on 20 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: lack of recruitment of patients). Results are not available in the source record.
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?
Respiratory mechanics (i.e. lung compliance, resistances and work of breathing) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Aug 2015.