Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial

Rationale: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. Objectives: We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). Methods: We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four postmenopausal women with PAH and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at 6 months. By intention-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Measurements and Main Results: Forty-one subjects were randomized to placebo and 43 to anastrozole, and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued the study drug. There was no significant difference in the change in 6MWD at 6 months (placebo-corrected treatment effect, -7.9 m; 95% confidence interval, -32.7 to 16.9; P = 0.53). There was no difference in adverse events between the groups. Conclusions: Anastrozole did not show a significant effect on 6MWD compared with placebo in postmenopausal women with PAH and in men with PAH. Anastrozole was safe and did not have adverse effects. Clinical trial registered with www.clincialtrials.gov (NCT03229499).