Effects of Bosentan on Respiratory Mechanics
Information source: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pulmonary Hypertension
Intervention: Bosentan (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi Official(s) and/or principal investigator(s): Stefano Nava, Principal Investigator, Affiliation: Fondazione S.Maugeri
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.
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)
Clinical Details
Official title: Effects of 12 Weeks Treatment With Bosentan on Respiratory Mechanics in Patients With Pulmonary Hypertension
Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label
Primary outcome: Respiratory mechanics (i.e. lung compliance, resistances and work of breathing)
Secondary outcome: exercise capacity (i.e. 6 mwd), dyspnea, oxygen saturation and cardiac function (i.e. hemodynamic evaluation)
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)
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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,
Exclusion Criteria:
- 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.
Locations and Contacts
Respiratory Unit, Fondazione S.Maugeri, Pavia, PV 27100, Italy
Additional Information
Starting date: May 2008
Last updated: August 19, 2015
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