PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is commonly complicated by pulmonary hypertension (PH). The objectives of this study were to assess the safety and efficacy of administering the inhaled prostacyclin analogue, iloprost(I), to patients with IPF and PH.
METHODS: In a double-blind, multicenter trial, IPF patients with NYHA functional class II-IV symptoms and elevated pulmonary arterial pressures (PAP) were randomized to receive inhaled iloprost (I, 2.5 μg or 5 μg per dose, 6 to 9 doses per day) or matching placebo (P) for a total of 12 weeks. PH was defined by an echocardiogram or right heart catheterization with right ventricular systolic pressure > 35 mm Hg, or mean PAP > 25 mm Hg. Enrollment criteria included a baseline 6 minute walk distance (6MWD) of 50 to 380 m. The primary endpoint was to assess the safety of the drug. Secondary efficacy endpoints were changes from baseline for: 6MWD, dyspnea/fatigue using the Borg scale, exercise-induced oxygen saturation, and clinical status.
RESULTS: 51 patients randomly received I (n=26) or P (n=25). The patients randomized to I were less severely impaired than those randomized to P (FC II: 46.2% I vs 28.0% P; median baseline 6MWD: 274.3 m I vs 235.0 m P). There were no deaths during the study, 6 I patients and 9 P patients discontinued prematurely, and the incidence of AEs was similar in both groups. There were no significant differences between I and P groups in change from baseline in 6MWD (–31m vs. 9.8m), NYHA Class (16% vs 13% improved), Borg Dyspnea score, and oxygen desaturation during exercise.
CONCLUSION: Daily inhalation therapy over 12 weeks with iloprost was well tolerated, but, in this small sample size and short duration study, did not meet secondary efficacy endpoints.
CLINICAL IMPLICATIONS: Although evidence for clinical benefit of prostacyclin inhalation therapy in IPF and PH was not shown, it appears safe to use such therapy if clinically indicated in specific cases.
DISCLOSURE: Michael Krowka, No Product/Research Disclosure Information; Grant monies (from industry related sources) Michael Mathier has received grant support from Actelion. Adaani Frost has received research grants and unrestricted educational grants from Actelion and Cotherix; Consultant fee, speaker bureau, advisory committee, etc. Shazad Ahmad is a consultant for Actelion. Michael Mathier is a consultant for Actelion, United Therapeutics and Gilead and serves on the speaker bureau for Actelion, United Therapeutics, Gilead and GlaxoSmithKline. Adaani Frost serves as a Steering Committee member for Actelion and has received honoraria and served on a speaker bureau for Actelion and Cotherix; Other Lisa Lancaster was Principal Investigator in a study funded by Actelion.