Safety and Efficacy of Imatinib Mesylate in Patients With Pulmonary Arterial Hypertension

Novartis Pharmaceuticals59 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Pulmonary Arterial Hypertension

Interventions

Imatinib mesylateDRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

Novartis Investigative Site

Los Angeles, California, United States

Novartis investigative site

Newark, New Jersey, United States

Novartis Investigative Site

New York, New York, United States

Outcomes

Primary Outcomes

Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Core

In this analysis patients with all (serious and non -serious) adverse events, and death were reported. See Safety Section.

Time frame: 6 months

Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Extension

In this analysis patients with all (serious and non -serious) adverse events, and death were reported. See Safety Section.

Time frame: 72 months

Change From Baseline of Six Minute Walk Test - Total Distance Walked at Different Time Periods

The Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Distance \<500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance \>800 meters (with no rests) suggests mild or no limitation.

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Change From Baseline of Six Minute Walk Test - Number of Stops at Different Time Periods

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Change From Baseline of Six Minute Walk Test - Total Duration of Stops at Different Time Periods

The Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. If the patient stopped the duration of each stop was recorded.

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of Patients With Pulmonary Hypertension (PAH) Assessd by World Health Organization (WHO) Classification on Physical Activity

PAH assessed according to the WHO classification: Class I Patients with PAH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope. Class II Patients with PAH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III Patients with PAH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope. Class IV Patients with PAH with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion

Borg Score-Oxygen Saturation(SaO2) During the Six Minutes Walk Test at Different Time Periods

Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. During the walk the patient was connected to a portable pulse oximeter via a finger probe. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. The test was terminated if the patient became too distressed or if their SaO2% fell below 60%.

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Borg Score-Systolic Blood Pressure During the Six Minutes Walk Test at Different Time Periods

Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. During the walk the patient was connected to a portable pulse oximeter via a finger probe. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Systolic blood pressure (mmHg) were recorded before the test at resting, at the end of the test and two minutes after the end of the test

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Borg Score-Diastolic Blood Pressure During the Six Minutes Walk Test at Different Time Periods

Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. During the walk the patient was connected to a portable pulse oximeter via a finger probe. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Diastolic blood pressure (mmHg) were recorded before the test at resting, at the end of the test and two minutes after the end of the test

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Borg Score-Heart Rate (HR) During the Six Minutes Walk Test at Different Time Periods

Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. During the walk the patient was connected to a portable pulse oximeter via a finger probe. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Heart Rate (bpm) were recorded before the test at resting, at the end of the test and two minutes after the end of the test

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Borg Score During the Six Minutes Walk Test at Different Time Periods

Borg Score during Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. During the walk the patient was connected to a portable pulse oximeter via a finger probe. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Borg Score of Breathlessness was recorded using the following score of 0 to 10, how breathless do you feel? 0 is nothing at all and 10 is maximal breathlessness

Time frame: Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Mean Pulmonary Artery Pressure (PAP) at Baseline and Study Completion

The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including right Pulmonary Arterial Pressure (PAP). Were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive Mean PAP and CO measurements within 10% of each other). PAP was assessed when the patient was breathing ambient air, every 2 minutes whilst breathing Nitric Oxide(NO) (1st and 2nd), 5 min after the end of NO administration, and 15 mins after the end of NO administration.