Multi-centre clinical trial of nedocromil sodium in reversible obstructive airways disease in adults: a general practitioner collaborative study

Abstract

The efficacy of nedocromil sodium (2 x 2 mg puffs twice a day) was assessed in a multi-centre, double-blind parallel group placebo-controlled study of 159 adult patients with chronic reversible obstructive airways disease. Over two-thirds of the patients had been maintained on or used an inhaled bronchodilator prior to the study. During a 4-week baseline period, patients stopped using their current respiratory therapy, with the exception of oral bronchodilators, and were established on a maintenance regimen of inhaled salbutamol (2 puffs 4-times daily with additional doses as needed). Patients then received either nedocromil sodium or placebo in place of the maintenance salbutamol regimen and inhaled salbutamol was allowed only on an as needed basis during a 12-week double-blind period. Daily diary records were made by patients of symptom severity, morning and evening peak expiratory flow rate, and salbutamol usage. The doctor assessed overall severity of the patient's condition at 4-weekly intervals, and both patients and doctor assessed treatment effectiveness at the end of the trial. Total symptom severity (night-time symptoms, morning tightness and daytime symptoms) was reduced and morning and evening PEFR improved throughout in the nedocromil sodium-treated patients, although evening PEFR returned nearly to the baseline in the final 4 weeks of the study. The reduction in combined day and night-time inhaled bronchodilator use from the baseline was significantly greater in the nedocromil sodium-treated patients and these patients were significantly (p less than 0.05) improved compared to the placebo-treated patients on each of the three occasions that the physicians assessed disease severity. Of the 40 patients withdrawn during the double-blind period of the study (26 on nedocromil sodium, 14 on placebo), 9 and 7 patients, respectively, were withdrawn because of the onset of uncontrolled asthma, and 4 and 2 patients, respectively, because of suspected adverse reactions to treatment. A total of 21 patients treated with nedocromil sodium recorded unusual symptoms (9 commented on taste, 5 had nausea and vomiting) compared with 16 patients on placebo. Overall, nedocromil sodium was considered to be moderately or very effective in at least 50% of the patients, although no significant differences were seen between treatments in either the patients' or physicians' assessment.