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)?


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.


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.


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


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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