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

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.

Figure 1. Screening, enrollment and interventions of the study participants.

COPD denotes chronic obstructive pulmonary disease, CVP central venous pressure, LVEF left ventricular ejection fraction, mPAP mean pulmonary artery pressure, PH pulmonary hypertension, sPAP systolic pulmonary artery pressure, 6MWT six-minute walking distance.

Figure 2. Improvement/worsening (in %) of outcome parameters in individual subjects after low dose iloprost inhalation (LD), high dose iloprost inhalation (HD) and placebo (PCB).

Parameters after placebo inhalation were considered 100%. Aa-gradient denotes alveolar-arterial oxygen gradient, HR heart rate, pCO₂ partial pressure of carbon dioxide after exercise, pO₂ partial pressure of oxygen, SpO₂ oxygen saturation, VCO₂ carbon dioxide production, VE minute ventilation, VO₂ oxygen consumption, 6MWD six-minute walking distance.