Imatinib (QTI571) in Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00902174
• Date of registration: 13/05/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Imatinib (QTI571) in Pulmonary Arterial Hypertension 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: September 2009
• Target sample size: 202
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00902174
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Canada, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Key Inclusion criteria

- Male or female patients =18 years of age with a current diagnosis of pulmonary
arterial hypertension (PAH) according to the Dana Point 2008 Meeting: World Health
Organization (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
following one year repair of congenital heart defect [Atrial Septal Defect (ASD),
Ventricular Septal Defect (VSD) or Posterior Descending Artery (PDA)], or PAH
associated with diet therapies or other drugs

- A Pulmonary Vascular Resistance (PVR) = 800 dynes.sec.cm-5 (as assessed by Right Heart
Catheterization (RHC) at screening or in the 3 months preceding the screening visit)
despite treatment with two or more specific PAH therapies, including Endothelin
Receptor Antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE5), or subcutaneous,
inhaled, intravenous or oral prostacyclin analogues for = 3 months. Background therapy
doses were to be stable for = 30 days except for warfarin and prostacyclin analogues (
= 30 days but doses could vary even within the month before enrollment).

- World Health Organization functional Class II-IV. For WHO Functional Class IV, one of
the 2 or more specific PAH therapies were to be an inhaled, subcutaneous, intravenous
or oral prostacyclin analogue, unless the subject showed intolerance of prostacyclin
analogues.

- 6MWD = 150 meters and = 450 meters at screening. Distances of two consecutive 6MWTs
were to be within 15% of one another.

Key Exclusion criteria

- With a pulmonary capillary wedge pressure > 15 mm Hg to rule out PAH secondary to left
ventricular dysfunction.

- With a diagnosis of pulmonary artery or vein stenosis

- Left ventricular ejection fraction (LVEF) < 45%

- With Disseminated Intravascular Coagulation (DIC)

- With evidence of major bleeding or intracranial hemorrhage

- With a history of elevated intracranial pressure

- With a history of latent bleeding risk such as diabetic retinopathy, gastrointestinal
bleeding due to gastric or duodenal ulcers, or colitis ulcerosa

- With a QTcF > 450 msec for males and > 470 msec for females at screening and baseline
in the absence of right bundle branch block.

- With a history of ventricular tachycardia, ventricular fibrillation or ventricular
flutter

- With a history of Torsades de Pointes

- With a history of long QT syndrome

- Having undergone atrial septostomy in the 3 months prior to the screening visit



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: imatinib mesylate

Drug: Placebo

Primary Outcome(s)

Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks [Time Frame: 24 weeks]

Secondary Outcome(s)

Change From Baseline in Systemic Vascular Resistance [Time Frame: baseline and week 24]

Plasma Concentration of QTI571 400 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant [Time Frame: predose and between 0 hour to 3 hour post dose at day 1, day 14, day 28 and day 168]

Change From Baseline in Cardiac Output [Time Frame: 24 weeks]

Change From Baseline in Mean Pulmonary Capillary Wedge Pressure [Time Frame: baseline and week 24]

Change From Baseline in Diastolic Arterial Blood Pressure [Time Frame: baseline and week 24]

Change From Baseline in Systolic Arterial Blood Pressure [Time Frame: baseline and week 24]

Change From Baseline in Heart Rate [Time Frame: 24 weeks]

Change From Baseline in Right Atrial Pressure [Time Frame: baseline and week 24]

Plasma Concentration of QTI571 200 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant [Time Frame: predose and between 0 hour to 3 hour post dose at day 1, day 14, day 28 and day 168]

Clinical Worsening Comparing Imatinib Versus Placebo for Adjudicated Cases [Time Frame: 24 weeks]

Change From Baseline in Mean Pulmonary Arterial Pressure [Time Frame: baseline and week 24]

Change From Baseline in Pulmonary Vascular Resistance [Time Frame: baseline and week 24]

Change From Baseline in Pulmonary Resistance Index [Time Frame: baseline and week 24]

Change in Borg Dyspnea Score During 6-minute Walk Test [Time Frame: week 24]

Covariance of End of Study CAMPHOR Score [Time Frame: Week 24]

Secondary ID(s)

CQTI571A2301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/07/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00902174