A randomized, controlled trial of bosentan in severe COPD

¹ Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Switzerland; and Harvard School of Public Health, Boston, Massachusetts, USA
² Division for Nuclear Medicine, University Hospital Basel, Switzerland
³ Cardiology, Hospital Winterthur, Switzerland
⁴ Cardiology, University Hospital Basel, Switzerland
⁵ Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Switzerland

^* To whom correspondence should be addressed. E-mail: dstolz{at}uhbs.ch.

	Abstract

Pulmonary hypertension during exercise is common in severe COPD. We hypothesized that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary hemodynamics during exercise, thus increasing exercise tolerance in patients with severe COPD.

In this double-blind, placebo-controlled study, 30 patients with severe or very severe COPD were randomly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks. The primary endpoint was change in the 6-minute walking distance. Secondary endpoints included changes in health-related quality of life, lung-function, cardiac hemodynamics, maximal oxygen uptake, and pulmonary perfusion patterns.

As compared to placebo, patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by 6-minute walking distance (331 m [123] versus 329 [94], p=0.474). There was no change in lung-function, pulmonary arterial pressure, maximal oxygen uptake, and regional pulmonary perfusion pattern (p=ns). In contrast, arterial oxygen pressure dropped (p=0.029), alveolar-arterial gradient increased (p=0.029), and quality of life deteriorated significantly in patients' assigned bosentan (p=0.039).

The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxemia and functional status in severe COPD patients without severe pulmonary hypertension at rest.