Study objectives: To assess the efficacy and safety of nedocromil sodium metered dose aerosol as an adjunct to sustained-released theophylline therapy in adult theophylline-dependent asthma patients and to examine the ability of nedocromil sodium to substitute for theophylline.
Design: Randomized double-blind placebo-controlled parallel group study. Two-week baseline, eight-week treatment period.
Setting: Out-Patient Clinic.
Patients: Sequential sample of 35 adult chronic asthmatic patients maintained on a regimen of sustained-release theophylline (dose range, 400 to 800 mg daily) and on-demand inhaled beta 2-bronchodilators. All patients completed the study.
Interventions: 2 x 2-mg nedocromil sodium metered dose aerosol twice daily or matching placebo randomly allocated after two-week baseline. Theophylline dose reduced by half or one third after four weeks of test treatments, then stopped for final two weeks. Use of inhaled beta 2-bronchodilators permitted throughout trial period.
Measurements and results: The following results were in favor (statistically significant findings, p less than 0.05) of nedocromil sodium compared with placebo: all diary card efficacy variables (nighttime asthma, morning tightness, daytime asthma, cough, twice daily peak expiratory flow [PEF], inhaled beta 2 use) during all periods of assessment (weeks 1 to 2, 3 to 4, 5 to 6, and 7 to 8) with the exception of cough and nighttime beta 2 use during weeks 1 to 2; patient and clinician opinion of treatment efficacy (end of weeks 4 and 8); ability to reduce the theophylline dose; clinician assessment of asthma severity at the end of the study, and clinic FEV1 at weeks 4, 5, 6, and 8. One placebo-treated patient reported transient moderately severe nausea and taste loss. No clinically significant changes were seen in the laboratory data.
Conclusion: Nedocromil sodium, 4 mg twice daily, conferred significant benefit when added to sustained-release theophylline therapy. The results suggest that nedocromil sodium may permit a reduction in theophylline dosage and possibly substitute for theophylline in previously dependent patients.