Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - a randomized controlled crossover trial

PLoS One. 2012;7(12):e52248. doi: 10.1371/journal.pone.0052248. Epub 2012 Dec 27.

Abstract

Background: Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).

Objectives: To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.

Methods: A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance.

Results: Both iloprost doses failed to improve six-minute walking distance (p = 0.36). Low dose iloprost (estimated difference of the means -1.0%, p = 0.035) as well as high dose iloprost (-2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p = 0.002 and p = 0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (-76 ml/min, p = 0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p = 0.040) and impaired ventilation during exercise (-3.0l/min, p<0.001).

Conclusions: Improvement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely.

Trial registration: Controlled-Trials.com ISRCTN61661881.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aerosols
  • Aged
  • Cross-Over Studies
  • Female
  • Humans
  • Hypertension, Pulmonary / complications*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Iloprost / administration & dosage*
  • Iloprost / metabolism
  • Iloprost / pharmacology*
  • Iloprost / therapeutic use
  • Male
  • Oxygen / metabolism
  • Pulmonary Disease, Chronic Obstructive / complications*
  • Pulmonary Gas Exchange / drug effects

Substances

  • Aerosols
  • Iloprost
  • Oxygen

Associated data

  • ISRCTN/ISRCTN61661881

Grants and funding

DS was supported by a grant from the Swiss National Foundation (PP00P3_128412/1). The trial was supported by an unrestricted grant from Bayer Schering. Additional funding was granted by the Clinic of Pulmonary Medicine, University Hospital Basel, Switzerland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.