Imatinib (QTI571) in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: imatinib mesylate; Placebo
Intervention description: Two or 4 imatinib mesylate (QTI571) 100 mg film coated tablets once daily.; Placebo to imatinib 100 mg film coated tablets
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pulmonary arterial hypertension; Imatinib; 6MWD; Borg scale; Pulmonary hypertension

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).
    

Eligibility 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