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.

DESIGN

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.