Clinical trial NCT00477269: Safety and Efficacy of Imatinib Mesylate in Patients With Pulmonary Arterial Hypertension
Official title: A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of the Six Months Treatment With the Tyrosine Kinase Inhibitor STI571 for the Treatment of Pulmonary Arterial Hypertension (PAH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension, tyrosine kinase inhibitor, STI571
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-05-23
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and efficacy of imatinib mesylate in patients with pulmonary arterial hypertension


Eligibility criteria: Inclusion Criteria:

* Diagnosis of PAH of either primary (idiopathic), familial or secondary to systemic sclerosis (excluding those with marked pulmonary fibrosis) according to World Conference on Pulmonary Hypertension classification (Venice, 2003).
* Symptoms with a WHO class of II-IV

Exclusion Criteria:

* Use of unspecific phosphodiesterase inhibitors (for example, pentoxyfillin, enoximon, milrinone or pimobendan) during the study
* Chronic inhaled nitric oxide therapy from start to study completion
* Treatment with catecholamines (for example, adrenalin, noradrenalin, dopamine),
* Pre-existing lung diseases, including parasitic diseases affecting lungs, asthma, congenital abnormalities of the lungs, chest, and diaphragm.
* Pulmonary artery or valve stenosis; pulmonary venous hypertension; chronic thromboembolic pulmonary hypertension
* Acute heart failure or chronic left sided heart failure; congenital or acquired valvular or myocardial disease
* Severe (systemic) arterial hypertension (\> 200 mmHg (systolic) or \> 120 mmHg (diastolic)) Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Core
timeFrame: 6 months
measure: Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Extension
timeFrame: 72 months
measure: Change From Baseline of Six Minute Walk Test - Total Distance Walked at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Change From Baseline of Six Minute Walk Test - Number of Stops at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Change From Baseline of Six Minute Walk Test - Total Duration of Stops at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
Secondary outcomes:
measure: Number of Patients With Pulmonary Hypertension (PAH) Assessd by World Health Organization (WHO) Classification on Physical Activity
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion
measure: Borg Score-Oxygen Saturation(SaO2) During the Six Minutes Walk Test at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Borg Score-Systolic Blood Pressure During the Six Minutes Walk Test at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Borg Score-Diastolic Blood Pressure During the Six Minutes Walk Test at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Borg Score-Heart Rate (HR) During the Six Minutes Walk Test at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Borg Score During the Six Minutes Walk Test at Different Time Periods
timeFrame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)
measure: Mean Pulmonary Artery Pressure (PAP) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Mean Pulmonary Artery Wedge Pressure (PAWP) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Mean Systolic Arterial Pressure (SAP) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Mean Heart Rate (HR) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Mean Cardiac Output (CO) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Mean Pulmonary Vascular Resistance (PVR) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Mean Systemic Vascular Resistance (SVR) at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Blood Gas Measurement - PaO2 at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Blood Gas Measurement - PaCO2 at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Blood Gas Measurement - PvO2 at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Blood Gas Measurement - Arterial Saturation at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Blood Gas Measurement - Venous Saturation at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
measure: Blood Gas Measurement - pH at Baseline and Study Completion
timeFrame: Baseline, and Study completion (Week 24)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Newark
country: United States
facility: Novartis investigative site
state: New Jersey
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Graz
country: Austria
facility: Novartis Investigative site
city: Giessen
country: Germany
facility: Novartis Investigative Site
city: Giessen
country: Germany
facility: Novartis Investigative site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
state: Cambridgeshire
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative site
city: Papworth
country: United Kingdom
facility: Novartis Investigative site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Investigative site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghofrani HA, Morrell NW, Hoeper MM, Olschewski H, Peacock AJ, Barst RJ, Shapiro S, Golpon H, Toshner M, Grimminger F, Pascoe S. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med. 2010 Nov 1;182(9):1171-7. doi: 10.1164/rccm.201001-0123OC. Epub 2010 Jun 25.