Imatinib (QTI571) in Pulmonary Arterial Hypertension
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Drug: Placebo
- Registration Number
- NCT00902174
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
A multinational, multicenter, double blind, placebo-controlled study evaluating the efficacy and safety of imatinib as an add-on therapy in the treatment of patients with severe pulmonary arterial hypertension (PAH).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 202
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description imatinib mesylate imatinib mesylate Imatinib mesylate (QTI571) 200 mg once daily for two weeks, increased to 400 mg once daily if well tolerated. If 400 mg dose was not well tolerated, a down titration to 200 mg once daily was permitted. Placebo Placebo Placebo to imatinib mesylate taken once daily. Participants receiving placebo were allowed to receive already approved PAH treatments.
- Primary Outcome Measures
Name Time Method Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks 24 weeks This standardized walk course was 30 meters in length. During the walk the participant was connected to a portable pulse oximeter via a finger probe. Participants were instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. The total distance walked (in meters) was recorded. Results were compared between the 2 groups.
- Secondary Outcome Measures
Name Time Method Clinical Worsening Comparing Imatinib Versus Placebo for Adjudicated Cases 24 weeks Clinical worsening per participant was measured by the onset of any adjudicated event (all cause mortality; overnight hospitalization for worsening of Pulmonary Arterial Hypertension (PAH); worsening of WHO functional class by one level; 15% decline in Six Minute Walk Distance (6MWD) measured on two consecutive occasions) at 24 weeks treatment, comparing imatinib to placebo groups. A cox regression analysis model was used.
Change From Baseline in Right Atrial Pressure baseline and week 24 Change from baseline in right atrial pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The right atrial pressure was assessed when the participant was in a stable hemodynamic rest state. A higher right atrial pressure number indicates worsening.
Change From Baseline in Mean Pulmonary Arterial Pressure baseline and week 24 Change from baseline in mean pulmonary arterial pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The mean pulmonary arterial pressure was assessed when the participant was in a stable hemodynamic rest state. A higher mean pulmonary arterial pressure number indicates worsening.
Change From Baseline in Mean Pulmonary Capillary Wedge Pressure baseline and week 24 Change from baseline in mean pulmonary capillary wedge pressure (mmHg)was measured via right heart catheterization according to the local hospital procedures. The right atrial mean pulmonary capillary wedge pressure was assessed when the participant was in a stable hemodynamic rest state.
Change From Baseline in Systemic Vascular Resistance baseline and week 24 Change from baseline in systemic vascular resistance (dynes\*sec\*cm\^-5) was measured via right heart catheterization according to the local hospital procedures. The systemic vascular resistance was assessed when the participant was in a stable hemodynamic rest state. Reduction from baseline in mean systemic vascular resistance indicates improvement.
Change From Baseline in Pulmonary Vascular Resistance baseline and week 24 Change from baseline in pulmonary vascular resistance (dynes\*sec\*cm\^-5) was measured via right heart catheterization according to the local hospital procedures. The pulmonary vascular resistance was assessed when the participant was in a stable hemodynamic rest state. Reduction from baseline in pulmonary vascular resistance indicates improvement.
Change From Baseline in Pulmonary Resistance Index baseline and week 24 Change from baseline in pulmonary resistance index (dynes\*sec\*cm\^-5/m2) was measured via right heart catheterization according to the local hospital procedures. The pulmonary resistance index was assessed when the participant was in a stable hemodynamic rest state. A reduction from baseline in pulmonary resistance index indicates improvement.
Change From Baseline in Cardiac Output 24 weeks Change from baseline in cardiac output (L/min) was measured via right heart catheterization according to the local hospital procedures. The cardiac output was assessed when the participant was in a stable hemodynamic rest state. An increase from baseline (higher number) in cardiac output indicates improvement.
Change From Baseline in Systolic Arterial Blood Pressure baseline and week 24 Change from baseline in systolic arterial blood pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The systolic arterial blood was assessed when the participant was in a stable hemodynamic rest state.
Change From Baseline in Diastolic Arterial Blood Pressure baseline and week 24 Change from baseline in diastolic arterial blood pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The diastolic arterial blood pressure was assessed when the participant was in a stable hemodynamic rest state.
Change From Baseline in Heart Rate 24 weeks Change from baseline in heart rate (bpm) was measured via right heart catheterization according to the local hospital procedures. The heart rate was assessed when the participant was in a stable hemodynamic rest state.
Change in Borg Dyspnea Score During 6-minute Walk Test week 24 Change in Borg scale was measured at different time points at week 24. The Borg Scale consists of scale range of 0 to 10. Participants pointed to indicate their level of dyspnea before and at the end of exercise testing (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness). A reduction in this score indicates an improvement.
Covariance of End of Study CAMPHOR Score Week 24 The CAMPHOR test consists of 65 items and 3 scales. Two scales measure Health Related Quality of Life. 1) Symptoms: consists of 25 items measuring loss or abnormality of psychological, physiological or anatomical structure or function; further sub-divided into 3 subscales (energy, breathlessness and mood), 2) Disability: consists of 15 items measuring any restriction or lack of ability to perform an activity. 3) Quality of Life (QOL): consists of 25 items defining how individuals perceived ability and capacity to satisfy their needs. The 25-item symptom and QOL scales score from 0-25 where a higher score indicates the presence of more symptoms and poor QOL, respectively. The 15-item functioning scale scores 0-30; a higher score indicates poor functioning.
Plasma Concentration of QTI571 200 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant predose and between 0 hour to 3 hour post dose at day 1, day 14, day 28 and day 168 Blood samples were taken from each subject participating in the study (placebo group and active treatment group) once predose and once between 0 hour to 3 hour post dose at day 1 (baseline), day 14, day 28 and day 168.
The parent compound QTI571 and its active metabolite, GCP74588, were measured in plasma by validated liquid chromatography-mass spectrometry (HPLC-MS/MS) assay.Plasma Concentration of QTI571 400 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant predose and between 0 hour to 3 hour post dose at day 1, day 14, day 28 and day 168 Blood samples were taken from each subject participating in the study (placebo group and active treatment group) once predose and once between 0 hour to 3 hour post dose at day 1 (baseline), day 14, day 28 and day 168.
The parent compound QTI571 and its active metabolite, GCP74588, were measured in plasma by validated liquid chromatography-mass spectrometry (HPLC-MS/MS) assay.
Trial Locations
- Locations (3)
Novartis Investigative Site
🇬🇧Sheffield, United Kingdom
University Hospital Basel
🇨ðŸ‡Basel, Switzerland
Novartis investigative site
🇪🇸Valencia, Spain