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
- Conditions
- Pulmonary arterial hypertension (PAH) patients who have a PVR>1000 dynes.sec.cm-5 despite treatment with two or more specific PAH therapiesMedDRA version: 9.1Level: LLTClassification code 10064911Term: Pulmonary arterial hypertension
- Registration Number
- EUCTR2009-012057-38-FR
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method