Effects of Bosentan (Tracleer) in the Course of Pulmonary Artery Hypertension Induced by Hypoxia

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00260819
First received: December 1, 2005
Last updated: October 16, 2008
Last verified: March 2007

December 1, 2005
October 16, 2008
January 2006
April 2008   (final data collection date for primary outcome measure)
To investigate whether bosentan compared to placebo reduces hypoxia-induced increase in pulmonary artery pressure in healthy subjects and in subjects with past history of high-altitude pulmonary oedema [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
To investigate whether bosentan compared to placebo reduces hypoxia-induced increase in pulmonary artery pressure in healthy subjects and in subjects with past history of high-altitude pulmonary oedema
Complete list of historical versions of study NCT00260819 on ClinicalTrials.gov Archive Site
  • To compare [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  • pulmonary artery pressure response to exercise, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  • exercise capacity, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  • oxygen desaturation, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  • and to assess the global safety [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  • To compare
  • - pulmonary artery pressure response to exercise,
  • - exercise capacity,
  • - oxygen desaturation,
  • and to assess the global safety
Not Provided
Not Provided
 
Effects of Bosentan (Tracleer) in the Course of Pulmonary Artery Hypertension Induced by Hypoxia
Effects of Bosentan (Tracleer) in the Course of Pulmonary Artery Hypertension Induced by Hypoxia

Excessive rise in pulmonary artery pressure induced by low oxygen tension (hypoxia) is one of the factors implicated in high-altitude pulmonary oedema. Plasma ET1 increases in subjects exposed to high altitude and is correlated to pulmonary artery pressure.

The aim of the study is to investigate whether blockade of ET1 receptors would reduce the acute rise in systolic pulmonary artery pressure induced by hypoxia.

Patients will be examined on a variable load supine bicycle ergometer. The exercise table will be tilted laterally by 20 to 30 degrees to the left. PASP will be assessed using Doppler echocardiography at rest and during during supine bicycle exercise in NORMOXIA and hypoxia. Exposure to normobaric hypoxia will be performed by breathing a hypoxic gas mixture at sea level during 90 minutes (12,3 % O2 + 87.7 % N2) reproducing conditions at 4300 m altitude. Exercise will be started at an initial workload of 40 watts and increased by 10 watts every minute to reach a workload level defined by a heart rate (HR) corresponding to 50% of the estimated maximal aerobic power

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypoxia-Induced Pulmonary Artery Hypertension
  • Drug: Bosentan
    Single dose administration of 250 mg bosentan (2 pills Tracleer 125 mg) or placebo
    Other Name: TRACLEER
  • Drug: Bosentam TRACLEER
    Single dose administration of 250 mg bosentan (2 pills Tracleer 125 mg) or placebo
    Other Name: Bosentam TRACLEER
  • Experimental: 1
    Experimental and Placebo Comparator administered in random order during to successive experimental phase
    Intervention: Drug: Bosentan
  • Placebo Comparator: 2
    Experimental and Placebo Comparator administered in random order during to successive experimental phase
    Intervention: Drug: Bosentam TRACLEER
Grunig E, Mereles D, Hildebrandt W, Swenson ER, Kubler W, Kuecherer H, Bartsch P. Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol. 2000 Mar 15;35(4):980-7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
April 2008
April 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 20 non smoker healthy volunteers : 10 resistant to high-altitude pulmonary oedema and 10 susceptible subjects, without history of cardiac or pulmonary disease or asthma, after a complete clinical examination and safety laboratory measurements prior to randomization, and after giving informed written consent.

Exclusion Criteria:

  • antecedent of lung disease notably with asthmatic antecedent or HTAP
  • antecedent of heart disease
  • female genital organ
  • systolic blood pressure < 85 mmHg or > 160 mmHg after 5 minutes of lengthened rest.
  • sentimentality in a medicine, in particular in a bosentan or in one of the excipients of the tablet.
  • hepatic incapacity moderated to severe correspondent in the class B or C of the classification of Child-Pugh (cf Pharmacokinetics) Rate serous hepatic aminotransferases, aspartate aminotransferases( ASAT) and\or alanine aminotransférases ( ALAT), superior to 3 times the superior limit of the normal before the started of the treatment.
  • pointed or chronic systematic diseases.
  • presence of antibody anti-HIV, of anti-HVC antibody, antigens Hbs and\or antibody anti-Hbc. - active addiction to smoking.
  • alcohol abuse and of toxins.
  • Taking of concomitant medicines except those allowed the chapter concomitant treatments.
  • signs, symptoms or values of the biological examinations situated except the clinically acceptable values for healthy subjects with or without antecedent of OPHA.
  • common(current) ingestion of excessive quantities of tea, coffee(cafe), chocolate and\or drinks containing some caffeine (> 5 cups / day, is approximately 500 mg of caffeine a day).
  • consumption of juice of grapefruit and\or herb tea on base of St.
  • John's wort
  • Don of blood in 3 months preceding the study.
  • Persons in period of exclusion on the national file of the persons lending itself to the biomedical search(research) without direct individual profit.
  • refusal or linguistic or psychic incapacity to sign the lit(enlightened) assent.
  • subject which can not submit itself to the constraints of the protocol (for example, not cooperative, incapable to go(surrender) to the visits of follow-up and probably incapable to finish the study
Male
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00260819
P050502, AOR05038
Yes
Isabelle Brindel, Department Clinical Research of Developpement
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: Michel AZIZI, MD,PhD Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
March 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP