Long-term effects of almitrine bismesylate in COPD patients with chronic hypoxaemia.

BACKGROUND: Almitrine bismesylate (AB) is a peripheral chemoreceptor agonist which is believed to improve oxygenation of COPD patients with chronic hypoxaemia, probably by improving the ventilation perfusion mismatch. We studied the long-term effects of AB in COPD patients with chronic hypoxaemia.

METHODS: Prospective, randomised, double-blind, placebo-controlled trial.

SETTING: Eight hundred bed teaching hospital with a catchment population of 350,000 inhabitants. PATIENT RECRUITMENT: COPD outpatients consulting between September 95 and September 99.

INCLUSION CRITERIA: (1) COPD (FEV1 < 50%). (2) PaO2 < or = 65 mmHg. (3) Stable arterial blood gases (ABG), spirometry (S) and clinical state.

EXCLUSION CRITERIA: Asthma, restrictive disease, sleep apnoea syndrome, advanced renal or hepatic disease, peripheral neuropathy, use of respiratory stimulants or psychotrophic drugs.

TREATMENT: AB 1 mg/kg/day (weight < 75 kg = 50 mg/day; weight > or = 75 kg = 100 mg/day) in an intermittent schedule with resting periods of 1 month after the third, 6th and 9th months during 1 year.

INSTRUMENTATION: Stabilisation period: S, ABG. Run-in period: S, ABG, 6-min walking test (WT), nocturnal pulse oximetry (NP) and quality of life evaluation (CRQ). Third, 6th and 9th months: S, ABG. End of the study: S, ABG, WT, NP, CRQ.

STATISTICS: ANOVA for repeated measurements.

RESULTS: Two hundred and eighty-nine patients were evaluated and 81 were included in the study. Sixty-six were followed for 6 months, 53 for 9 months and 42 for 1 year. Almitrine and placebo groups did not present significant differences in ABG and S in the 6th, 9th and 12th months. Evolution in WT, NP and CRQ were similar in the two groups. No relevant side-effects were detected: only two patients stopped treatment (one placebo and one AB).

CONCLUSION: In an intermittent schedule, although well tolerated, at doses of 1 mg/kg/day, AB was not effective in long-term treatment of chronic hypoxemia in COPD patients.