Effects of Bosentan on Respiratory Mechanics

Pulmonary Hypertension Clinical Trial

Official title:

Effects of 12 Weeks Treatment With Bosentan on Respiratory Mechanics in Patients With Pulmonary Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00679068
• Other study ID #: 525FSM
• Status: Terminated
• Phase: Phase 4
• First received: May 14, 2008
• Last updated: August 19, 2015
• Start date: May 2008
• Est. completion date: June 2013

Study information

• Verified date: August 2015
• Source: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical 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.

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)

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Bosentan
62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.for the remaining 8 weeks (if tolerated)

Locations

Country	Name	City	State
Italy	Respiratory Unit, Fondazione S.Maugeri	Pavia	PV

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory mechanics (i.e. lung compliance, resistances and work of breathing)		12 weeks	No
Secondary	exercise capacity (i.e. 6 mwd), dyspnea, oxygen saturation and cardiac function (i.e. hemodynamic evaluation)		12 weeks	No