BREATHE-5 was the first randomized, double-blind, placebo-controlled trial in adult patients with PAH associated with Eisenmenger syndrome (N=54)1
Design
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Dosing and duration
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Randomized, double-blind, placebo-controlled study
of 54 patients with PAH associated
with Eisenmenger syndrome. Patients were randomized to Tracleer (n=37) or placebo
(n=17).
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Tracleer 62.5 BID first 4 weeks
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Tracleer 125 mg BID following 12 weeks
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Primary endpoints
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Secondary endpoints
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PVRi
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Change in oxygen saturation at week 16
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Change in exercise capacity
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Change in hemodynamics
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Change in functional class
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PAH etiology (Tracleer treatment group)
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Background therapies
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CHD: 37 (100%)
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—
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ASD: 8 (22%)
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—
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VSD: 24 (65%)
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—
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ASD + VSD: 5 (14%)
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Anticoagulants
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Vasodilators
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Diuretics
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Supplemental oxygen
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Baseline functional class status
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Baseline characteristics
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FC III: 100%
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Atrial septal defect (ASD) ≥2 cm (n=13); ventricular septal defect (VSD) ≥1 cm (n=36);
ASD + VSD (n=5)
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Results
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Reduces PVRi1
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Improved exercise capacity1
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No increase in shunting
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Results confirm that Tracleer did not worsen the shunt, an important safety consideration
in Eisenmenger syndrome.1
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No significant change in oxygen saturation from baseline to 16 weeks (82.4% ± 5.3%,
baseline; 83.8% ± 5.5%, week 16)2
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Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in
patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of
clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical
deterioration and a trend for improvement in walk distance. Physicians should consider whether
these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may
preclude future use as their disease progresses.
Important safety information
Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.
Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure
and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients
is essential prior to initiation of treatment and monthly thereafter.
High potential for major birth defects—Pregnancy must be excluded and prevented through the use of
reliable forms of birth control; monthly pregnancy tests should be obtained.
Contraindicated for use with cyclosporine A and glyburide.
Please see full prescribing information including BOXED WARNING.
- Galiè N, Beghetti M, Gatzoulis MA, et al, for the Bosentan Randomized Trial of Endothelin
Antagonist Therapy-5 (BREATHE-5) Investigators. Bosentan therapy in patients with
Eisenmenger syndrome: a multicenter, double-blind, randomized, placebocontrolled
study. Circulation. 2006;114:48-54.
- Data on file, Actelion Pharmaceuticals.
