Phase 3 N=202 Randomized Quadruple-blind Treatment

Imatinib (QTI571) in Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension

Bottom Line

View on ClinicalTrials.gov: NCT00902174 ↗

Enrolled (actual)

202

Serious AEs

36.8%

Results posted

Jul 2013

Primary outcome: Primary: Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks — 382.94; 351.18 meters

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: imatinib mesylate (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Novartis Pharmaceuticals
Primary completion: May 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks	382.94; 351.18	—
SECONDARY Clinical Worsening Comparing Imatinib Versus Placebo for Adjudicated Cases	35.9; 32.7	—
SECONDARY Change From Baseline in Right Atrial Pressure	-1.02; 0.68	—
SECONDARY Change From Baseline in Mean Pulmonary Arterial Pressure	-3.54; 1.63	—
SECONDARY Change From Baseline in Mean Pulmonary Capillary Wedge Pressure	0.92; -0.05	—
SECONDARY Change From Baseline in Systemic Vascular Resistance	-467.84; -88.10	—
SECONDARY Change From Baseline in Pulmonary Vascular Resistance	-366.47; 12.12	—
SECONDARY Change From Baseline in Pulmonary Resistance Index	-221.29; 21.92	—
SECONDARY Change From Baseline in Cardiac Output	1.17; 0.29	—
SECONDARY Change From Baseline in Systolic Arterial Blood Pressure	-2.92; -1.15	—
SECONDARY Change From Baseline in Diastolic Arterial Blood Pressure	-3.81; -1.48	—
SECONDARY Change From Baseline in Heart Rate	0.38; 0.73	—
SECONDARY Change in Borg Dyspnea Score During 6-minute Walk Test	-0.06; -0.12; -0.38; -0.24; -0.37; -0.18	—
SECONDARY Covariance of End of Study CAMPHOR Score	7.93; 9.03; 8.99; 10.55; 7.45; 7.13	—
SECONDARY Plasma Concentration of QTI571 200 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant	0; 0; 471.9; 61.8; 579.6; 178.8	—
SECONDARY Plasma Concentration of QTI571 400 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant	0; 0; 843.2; 109.9; 516.5; 155.1	—

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) 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00902174). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.