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

Abstract

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 (PaO₂) 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 PaO₂ 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 PaO₂ 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 PaO₂ 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 PaO₂ 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.