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Pulmonary Arterial HypertensionPhase 2/3NCT00477269

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

A Phase 2/3 study testing Imatinib mesylate in people with Pulmonary Arterial Hypertension, run by Novartis Pharmaceuticals at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
Imatinib mesylate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
59 participants
Where
13 sitesin 4 countries
Study dates
Apr 2006to Jan 2014
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

Germany4 sites
  • Novartis Investigative Site

    Giessen, 35385

  • Novartis Investigative site

    Giessen

  • Novartis Investigative Site

    Hanover, Germany, 30625

  • Novartis Investigative site

    Hanover

Other trials in Germany

United Kingdom4 sites
  • Novartis Investigative Site

    Cambridge, Cambridgeshire, CB23 3RE

  • Novartis Investigative Site

    Glasgow, G11 6NT

  • Novartis Investigative site

    Glasgow

  • Novartis Investigative site

    Papworth Everard

Other trials in United Kingdom

United States3 sites
  • Novartis Investigative Site

    Los Angeles, California, 90073

  • Novartis Investigative Site

    New York, New York, 10032

  • Novartis investigative site

    Newark, New Jersey, 07112

Other trials in United States

Austria2 sites
  • Novartis Investigative Site

    Graz, Austria, A-8036

  • Novartis Investigative site

    Graz

Other trials in Austria

About this study

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)

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

Being tested
Imatinib mesylate, Placebo
Keywords
Pulmonary Arterial Hypertension, tyrosine kinase inhibitor, STI571
Medical subject headings
Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Imatinib mesylateDrug

    Also called Imatinib, Glivec, Gleevec, STI571, QTI571

  • PlaceboDrug

Study groups in NCT00477269
Study groupRoleWhat they receive
STI571ExperimentalSTI571
Receives: Drug: Imatinib mesylate
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Placebo
All PatientsExperimentalOpen label extension
Receives: Drug: Imatinib mesylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 6 months

  2. 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.

    Measured: 72 months

  3. 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.

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

  4. Change From Baseline of Six Minute Walk Test - Number 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. Number of stops were recorded for each patient.

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

  5. 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.

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

Secondary outcomes (19)
  1. 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.

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

  2. 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%.

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

  3. 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

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

  4. 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

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

  5. 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

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

  6. 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

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

  7. 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.

    Measured: Baseline, and Study completion (Week 24)

  8. Mean Pulmonary Artery Wedge Pressure (PAWP) at Baseline and Study Completion

    The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Arterial Wedge Pressure (PAWP). 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.

    Measured: Baseline, and Study completion (Week 24)

  9. Mean Systolic Arterial Pressure (SAP) at Baseline and Study Completion

    The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including Systolic Arterial Pressure (SAP). 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.

    Measured: Baseline, and Study completion (Week 24)

  10. Mean Heart Rate (HR) at Baseline and Study Completion

    The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including Heart Rate (HR). 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.

    Measured: Baseline, and Study completion (Week 24)

  11. Mean Cardiac Output (CO) at Baseline and Study Completion

    The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including Cardiac Output (CO). 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.

    Measured: Baseline, and Study completion (Week 24)

  12. Mean Pulmonary Vascular Resistance (PVR) at Baseline and Study Completion

    The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Vascular Resistance (PVR). 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. PVR calculated according to the equation:PVR = (PAP - PCWP)/CO

    Measured: Baseline, and Study completion (Week 24)

  13. Mean Systemic Vascular Resistance (SVR) at Baseline and Study Completion

    The right heart catheter assessment was performed to assess several prognostic hemodynamic variables in pulmonary hypertension, including Systemic Vascular Resistance (SVR). 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. SVR was calculated according to the equation: SVR = (Paorta - Pright atrium)/CO

    Measured: Baseline, and Study completion (Week 24)

  14. Blood Gas Measurement - PaO2 at Baseline and Study Completion

    The right heart catheter assessment was performed to assess Blood Gas Measurements in pulmonary hypertension, including PaO2 levels at baseline and Study completion Week 24.

    Measured: Baseline, and Study completion (Week 24)

  15. Blood Gas Measurement - PaCO2 at Baseline and Study Completion

    The right heart catheter assessment was performed to assess Blood Gas Measurements in pulmonary hypertension, including PaCO2 levels at baseline and Study completion Week 24.

    Measured: Baseline, and Study completion (Week 24)

  16. Blood Gas Measurement - PvO2 at Baseline and Study Completion

    The right heart catheter assessment was performed to assess Blood Gas Measurements in pulmonary hypertension, including PvO2 levels at baseline and Study completion Week 24.

    Measured: Baseline, and Study completion (Week 24)

  17. Blood Gas Measurement - Arterial Saturation at Baseline and Study Completion

    The right heart catheter assessment was performed to assess Blood Gas Measurements in pulmonary hypertension, including Arterial Saturation levels at baseline and Study completion Week 24.

    Measured: Baseline, and Study completion (Week 24)

  18. Blood Gas Measurement - Venous Saturation at Baseline and Study Completion

    The right heart catheter assessment was performed to assess Blood Gas Measurements in pulmonary hypertension, including Venous Saturation levels at baseline and Study completion Week 24.

    Measured: Baseline, and Study completion (Week 24)

  19. Blood Gas Measurement - pH at Baseline and Study Completion

    The right heart catheter assessment was performed to assess Blood Gas Measurements in pulmonary hypertension, including pH levels at baseline and Study completion Week 24. The pH scale measures how acidic or basic a substance is. It ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic.

    Measured: Baseline, and Study completion (Week 24)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2007 (estimated)
  2. Study startApr 2006
  3. Primary completionJan 2014
  4. Study completionJan 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00477269
Sponsor's protocol ID
CSTI571E2203
Other IDs
2005-005569-12, 2005
Status last verified
Mar 2015
First submitted
22 May 2007
Last updated
23 Mar 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20581169

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Imatinib mesylate in people with Pulmonary Arterial Hypertension, run by Novartis Pharmaceuticals at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Germany, United Kingdom, United States, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Core (time frame: 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00477269, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2015.

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