Effects of almitrine bismesylate on arterial blood gases in patients with chronic obstructive pulmonary disease and moderate hypoxaemia: a multicentre, randomised, double-blind, placebo-controlled study.
BACKGROUND
Advanced chronic obstructive pulmonary disease (COPD) generates high costs, especially when patients require domiciliary long-term oxygen therapy (LTOT). Almitrine bismesylate has been shown to improve gas exchange in the lungs. Our hypothesis was that long-term treatment with almitrine might postpone the prescription of LTOT.


OBJECTIVE
To evaluate the effects of almitrine sequential treatment on arterial blood gases in COPD patients with moderate hypoxaemia.


METHODS
COPD patients with moderate hypoxaemia [partial oxygen tension in arterialised blood (PaO(2)) between 7.33 and 8.66 kPa (56-65 mm Hg)] were investigated. After a 1-month run-in period, patients were given either almitrine 100 mg per day or placebo for sequential treatment for a total of 12 months.


RESULTS
115 patients in a steady state (57 in the almitrine and 58 in the placebo group) were included. Mean age was 60 years, mean forced expiratory volume in 1 s was 34 +/- 13% of predicted and mean PaO(2) was 8.04 +/- 0.5 kPa (60.5 +/- 3.8 mm Hg). 38 patients were lost to follow-up, 23 in the almitrine and 15 in the placebo group. The majority of drop-outs were due to adverse events (AE; 16 in the almitrine and 9 in the placebo group). Almitrine treatment resulted in PaO(2) improvement of 0.43 +/- 0.88 kPa (3.2 +/- 6.6 mm Hg) (p = 0.003). The treatment effect between almitrine and placebo was 0.45 kPa (3.4 mm Hg) (p = 0.003). In the almitrine group, two distinct subgroups were observed: responders (n = 19) and non-responders (n = 38). Almitrine treatment in responders resulted in a clinically significant improvement in PaO(2) of 1.36 +/- 0.7 kPa (10.2 +/- 5.3 mm Hg) (p < 0.0001) and a reduction of partial carbon dioxide tension in arterialised blood. 31 patients experienced serious AE: 17 in the almitrine and 14 in the placebo group. Five patients died during the study (3 in the almitrine and 2 in the placebo group). Most AE occurring during the study were related to underlying disease. Clinical diagnosis of polyneuropathy resulted in the withdrawal of 5 patients in the almitrine group and 3 patients in the placebo group. Four patients in the almitrine group experienced weight loss.


CONCLUSIONS
Almitrine treatment of patients with severe COPD and moderate hypoxaemia resulted in a small but significant improvement in PaO(2) over 12 months. A clinically important improvement in gas exchange was observed in 33% of treated patients. These patients may be candidates for long-term treatment.
Górecka
D
D
Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. d.gorecka@igichp.edu.pl
Sliwiński
P
P
Pałasiewicz
G
G
Pachocki
R
R
Zieliński
J
J
D000368:Aged; D015765:Almitrine / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D019141:Respiratory System Agents / Q000494:pharmacology*
D019141:Respiratory System Agents; D002245:Carbon Dioxide; D015765:Almitrine; D010100:Oxygen