Imatinib (QTI571) in Pulmonary Arterial Hypertension (IMPRES)

Novartis

Status and phase: Completed; Phase 3

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Placebo; Drug: imatinib mesylate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00902174

CQTI571A2301

Details and patient eligibility

About

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).

Enrollment: 202 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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202 participants in 2 patient groups, including a placebo group

imatinib mesylate

Experimental group

Description:

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.

Treatment:

Drug: imatinib mesylate

Placebo

Placebo Comparator group

Description:

Placebo to imatinib mesylate taken once daily. Participants receiving placebo were allowed to receive already approved PAH treatments.

Treatment:

Drug: Placebo