Effects of Bosentan on Respiratory Mechanics

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
dr. Stefano Nava, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov Identifier:
NCT00679068
First received: May 14, 2008
Last updated: July 16, 2012
Last verified: July 2012
  Purpose

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)


Condition Intervention Phase
Pulmonary Hypertension
Drug: Bosentan
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Effects of 12 Weeks Treatment With Bosentan on Respiratory Mechanics in Patients With Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:

Primary Outcome Measures:
  • Respiratory mechanics (i.e. lung compliance, resistances and work of breathing) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • exercise capacity (i.e. 6 mwd), dyspnea, oxygen saturation and cardiac function (i.e. hemodynamic evaluation) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: May 2008
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
treatment with Bosentan
Drug: Bosentan
62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.for the remaining 8 weeks (if tolerated)

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00679068

Contacts
Contact: Stefano Nava, MD 39 0382 592 ext 806 stefano.nava@fsm.it
Contact: Piero Ceriana, MD 39 0382 592 ext 804 piero.ceriana@fsm.it

Locations
Italy
Respiratory Unit, Fondazione S.Maugeri Recruiting
Pavia, PV, Italy, 27100
Contact: Stefano Nava, MD    39 0382 592 ext 806    stefano.nava@fsm.it   
Contact: Piero Ceriana, MD    39 0382 592 ext 804    piero.ceriana@fsm.it   
Principal Investigator: Stefano Nava, MD         
Sponsors and Collaborators
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Investigators
Principal Investigator: Stefano Nava Fondazione S.Maugeri
  More Information

No publications provided

Responsible Party: dr. Stefano Nava, Chief ICU, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov Identifier: NCT00679068     History of Changes
Other Study ID Numbers: 525FSM
Study First Received: May 14, 2008
Last Updated: July 16, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:
respiratory mechanics
bosentan
exercise capacity

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014