Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan: A Parallel, Randomized Trial

Study Questions:

Does ambrisentan reduce the rate of progression of idiopathic pulmonary fibrosis (IPF)?

Methods:

This was a randomized, double-blind, placebo-controlled, multicenter, international trial. Eligible participants were men and women, ages 40-80 years, who had a diagnosis of IPF for at least 3 months; those with >5% honeycombing on high-resolution computed tomography were excluded. The composite primary endpoint was time to IPF disease progression, defined as whichever of the following occurred first: death from any cause, hospitalization due to adjudicated respiratory events, or a categorical decrease in lung function.

Results:

The study was terminated early after enrollment of 492 patients (75% of intended) because an interim analysis suggested a low likelihood of showing efficacy for the endpoint by the conclusion of the study. More patients had disease progression in the ambrisentan group (n = 90 [27.4%]) than in the placebo group (n = 28 [17.2%]) (p = 0.010). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) in the ambrisentan and placebo groups, respectively (p = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (p = 0.100). An analysis stratified by the presence of pulmonary hypertension yielded similar results.

Conclusions:

The authors concluded that ambrisentan was not effective in treating IPF, and may be associated with accelerated disease progression.

Perspective:

This multicenter, prospective study provides convincing evidence that ambrisentan is ineffective as a treatment for patients with IPF, and may actually increase the likelihood of disease progression. It should not be used in this population, and should not be evaluated further as a therapeutic option for this disease entity.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pulmonary Hypertension and Venous Thromboembolism, Pulmonary Hypertension, Computed Tomography, Nuclear Imaging

Keywords: DNA-Activated Protein Kinase, Tomography, X-Ray Computed, Idiopathic Pulmonary Fibrosis, Hypertension, Pulmonary, Phenylpropionates, DNA Repair, Disease Progression, Pyridazines


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