Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension

Chronic Thromboembolic Pulmonary Hypertension Clinical Trial

Official title:

Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00313222
• Other study ID #: AC-052-366
• Status: Completed
• Phase: Phase 3
• First received: April 10, 2006
• Last updated: February 11, 2010
• Start date: October 2005
• Est. completion date: March 2007

Study information

• Verified date: February 2010
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The present trial investigates a possible use of oral bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH), to patients suffering from inoperable chronic thromboembolic pulmonary hypertension (CTEPH) because of (i) peripheral localization of thrombotic material or (ii) persistent or recurrent pulmonary hypertension after pulmonary endarterectomy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: March 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Symptomatic pulmonary hypertension in modified NYHA functional class II to IV due to CTEPH as demonstrated by ventilation/perfusion lung scanning and pulmonary angiography.

• CTEPH judged inoperable because of peripheral localization of thrombotic material or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) with no evidence of recurrent thromboembolism and not amenable to repeated surgery.

• 6-minute walk test (6MWT) distance < 450 m.

• Hemodynamic evaluation showing: Mean pulmonary arterial pressure (mPAP) >= 25 mmHg; Pulmonary capillary wedge pressure (PCWP) < 15 mmHg; Pulmonary vascular resistance (PVR) at rest >= 300 dyn×sec/cm5

• For patients who underwent PEA, hemodynamic evaluation must have been performed more than 6 months after PEA.

• For all patients, hemodynamic evaluation must have been performed with the 3 months immediately preceding inclusion.

• Men or women >= 18 and =< 80 years of age (Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception).

• Anticoagulants at efficacious dose for at least 3 months prior to randomization.

• Signed informed consent prior to initiation of any study-mandated procedure.

Exclusion Criteria:

• Other forms of pulmonary hypertension including pulmonary hypertension related to sickle cell disease.

• Obstructive lung disease: FEV1/FVC < 0.5 after bronchodilator.

• Severe restrictive lung disease: Total Lung Capacity < 60% of predicted value.

• Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication.

• Symptomatic pulmonary embolism within 6 months prior to randomization.

• Pulmonary endarterectomy within 6 months prior to randomization.

• Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.

• Illness with a life expectancy of less than 6 months.

• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.

• AST and/or ALT > 3 times the upper limit of normal ranges.· Hemoglobin concentration < 75% the lower limit of normal ranges.

• Pregnancy or breast-feeding.

• Systolic blood pressure (BP) < 85 mmHg.

• Treatment or planned treatment with another investigational drug and/or pulmonary angioplasty within 3 months prior to randomization.

• Treatment with an endothelin receptor antagonist, a phosphodiesterase inhibitor, L-arginine or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months prior to randomization.

• Treatment for pulmonary hypertension within 1 month prior to randomization, excluding calcium channel blockers if present for at least 1 month before randomization.

• Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, glibenclamide (glyburide) within 1 week prior to randomization.

• Known hypersensitivity to bosentan or any of the excipients.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• bosentan

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Brisbane
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	General Hospital of Vienna	Vienna
Belgium	University Hospital Erasme	Brussels
Belgium	University Hospital Gathuisberg	Leuven
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Centre de Pneumonologie de L'Hospital Laval	Sainte-Foy	Quebec
Canada	University of Western Ontario	Sainte-Foy	Quebec
Canada	Toronto General Hospital Pulmonary & Critical Care Medicine	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Czech Republic	Charles University, Internal Medicine Department, (PAH unit)	Praha 2
France	Hopital Cardiologique Louis-Pradel	Bron Cedex
France	Hopital Antoinw Beclere	Clamart
Germany	University Hospital Giessen	Giessen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Johannes Gutenberg University Hospital	Mainz
Italy	Policlinico S. Orsola-Malpighi	Bologna
Italy	Azienda Ospedailera San Luigi	Orbassano
Italy	San Matteo Hospital	Pavia
Italy	Ospedale di Cattinara	Trieste
Netherlands	Academic Medical Center	Amsterdam
Netherlands	St. Antonius Ziekennuis	Nieuwegein
Poland	Medical University of Warsaw	Warszawa
Spain	Hospital Clinico i Provincial	Barcelona
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Western Infirmary	Glasgow
United States	Duke University Medical Center	Durham	North Carolina
United States	University of California at San Diego	LaJolla	California
United States	Mayo Clinic, Division of Cardiovascular Diseases and Internal Medicine	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Week 16 in 6-Minute Walk Test distance		Week 16
Primary	Change from Baseline to Week 16 in Pulmonary Vascular Resistance at rest		Week 16
Secondary	Change from Baseline to Week 16 in modified NYHA functional class		Week 16
Secondary	Time to clinical worsening		Time to clinical worsening