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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 28 August 2012
Main ID:  EUCTR2009-012057-38-NL
Date of registration: 23/11/2009
Prospective Registration: Yes
Primary sponsor: Novartis Pharma AG
Public title: A 24-week randomized placebo-controlled, double-blind multi-center clinical trial evaluating the efficacy and safety of oral QTI571 as an add-on therapy in the treatment of severe pulmonary arterial hypertension: Imatinib in Pulmonary arterial hypertension, a Randomized, Efficacy Study - IMPRES
Scientific title: A 24-week randomized placebo-controlled, double-blind multi-center clinical trial evaluating the efficacy and safety of oral QTI571 as an add-on therapy in the treatment of severe pulmonary arterial hypertension: Imatinib in Pulmonary arterial hypertension, a Randomized, Efficacy Study - IMPRES
Date of first enrolment: 05/01/2010
Target sample size: 200
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012057-38
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no  
Phase: 
Countries of recruitment
Austria Belgium France Germany Italy Netherlands Spain Sweden
United Kingdom
Contacts
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Key inclusion & exclusion criteria
Inclusion criteria:
1) Male or female 18 years of age or older
2) A current diagnosis of Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH associated systemic sclerosis, PAH following one year repair of congenital heart defect (ASD, VSD or PDA), or PAH associated with diet therapies or other drugs
3) A PVR>1000 dynes.sec.cm-5 despite treatment with two or more specific PAH therapies, including endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitors (PDE5), or inhaled, intravenous or oral prostacyclin analogues for = 3 months. On stable background therapy doses for = 30 days except for warfarin ( = 30 days but doses can vary even within the month before enrollment)
4) WHO Functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies must be an inhaled, intravenous or oral prostacyclin analogue, unless the subject has been shown to be intolerant of prostacyclin analogues.
5) 6MWD = 150 meters and = 450 meters at screening. Distances of two consecutive 6MWTs should be within 15% of one another.
6) Ability to provide written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
The following patients will be excluded from participation in the study:
1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are
a. women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
b. women whose partners have been sterilized by vasectomy or other means
c. two birth control methods.
2. Pregnant or nursing (lactating) women
3. have previously received treatment with imatinib
4. in treatment with chronic nitric oxide therapy
5. pre-existing lung disease
6. with a pulmonary capillary wedge pressure > 15 mm Hg to rule out PAH secondary to left ventricular dysfunction
7. with a diagnosis of pulmonary artery or vein stenosis
8. with a diagnosis of chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV)
9. with deficient thrombocyte function, thrombocytopenia < 50 x109/L
10. with a history acute heart failure or chronic left sided heart failure
11. with ucontrolled systemic arterial hypertension, systolic > 160 mmHg or diastolic >90 mmHg
12. with hemoglobin < 100 g/L
13. with deficiencies of blood coagulation, inherited or acquired blood coagulation disorders, factor XII, factor XIII; decreased generation of coagulation factors due to acute or chronic liver diseases, efficient coagulation due to auto-antibodies against coagulation factors such as in lupus anticoagulant
14. with disseminated intravascular coagulation (DIC)
15. with evidence of major bleeding or intracranial hemorrhage
16. with a history of elevated intracranial pressure
17. with a history of latent bleeding risk such as diabetic retinopathy, gastrointestinal bleeding due to gastric or duodenal ulcers, or colitis ulcerosa
18. with a history of moderate or greater hepatic insufficiency transaminase levels > 4 times the upper limit of normal or a bilirubin > 2 times the upper limit of normal
19. with a history of renal insufficiency (serum creatinine > 200 µmol/l)
20. previous therapeutic radiation of lungs or mediastinum
21. with a history of sickle cell anemia
22. with a QTcF > 450 msec for males and > 470 msec for females at screening
23. with a history of ventricular tachycardia, ventricular fibrillation or ventricular flutter
24. having a syncope in the 3 months prior to the screening visit
25. with a history of Torsades de Pointes
26. with a history of long QT syndrome
27. having undergone atrial septostomy in the 3 months prior to the screening visit
28. having undergone radiofrequency catheter ablation for atrial or sinus arrhythmias in the 3 months prior to screening visit
29. with an advanced, severe, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations
30. with a history of immunodeficiency diseases, including HIV
31. with a known hypersensitivity to QTI571 or drugs similar to the study drug
32. with a disability that may prevent the patient from completing all study requirements and in particular, interfere with the 6MWD assessment
33. with a life expectancy of 6 months or less
34. having used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
35. with a history of malignancy of any organ system, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
36. With a diagnosis of Hepatitis B or C
37. With a history of alcohol abuse within 6 months of screening
38. With a history of


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Pulmonary arterial hypertension (PAH) patients who have a PVR>1000 dynes.sec.cm-5 despite treatment with two or more specific PAH therapies
MedDRA version: 9.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension
Intervention(s)

Trade Name: Glivec®
Product Code: QTI571
Pharmaceutical Form: Tablet
INN or Proposed INN: IMATINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: • To evaluate the efficacy of QTI571 compared to placebo as measured by the change in 6-minute walk distance (6MWD) from baseline to 24-weeks
Primary end point(s): • 6MWD – a marker of exercise tolerance (the distance walked in 6 minutes during a 6-minute walk test according to ATS guidelines)
Secondary Objective: • To evaluate the time to clinical worsening (TTCW), including all cause mortality, overnight hospitalization for worsening PAH for at least 24 hours (established by external adjudication committee), worsening of WHO functional class and a drop in 6MWD by 15% during 24 weeks of treatment with QTI571 as compared to placebo
• To assess the safety and tolerability of QTI571
• To evaluate change in pulmonary hemodynamics from baseline in patients after 24 weeks of treatment with QTI571 as compared to placebo
• To assess change in Borg dyspnea score during 6-minute walk testing (6MWT), monthly, with QTI571 as compared to placebo.
• To assess the pharmacokinetics of QTI571 and the potential for interaction of QTI571 on sildenafil and bosentan
?• To assess the pharmacogenetics of QTI571
• To assess the use of different possible definitions of time TTCW as a measure of efficacy in treatment of PAH
Secondary Outcome(s)
Secondary ID(s)
2009-012057-38-DE
CQTI571A2301
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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