Effects of the addition of nedocromil sodium to maintenance bronchodilator therapy in the management of chronic asthma.

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.