A COMPARISON OF INHALED IPRATROPIUM, ORAL THEOPHYLLINE PLUS INHALED BETA-AGONIST, AND THE COMBINATION OF ALL 3 IN PATIENTS WITH COPD

To evaluate the role of inhaled ipratropium bromide alone vs oral theo phylline plus inhaled beta-agonist or the combination of all three in patients with stable COPD, the following double-blind, placebo-control led study was conducted. Forty-eight patients with stable COPD (mean a ge, 61.8 years, with mean baseline FEV(1)<1.0 L) were randomized on fo ur separate days to receive the following drug regimens: (1) theophyll ine, tablets (dose previously determined to result in blood level of 1 2 to 18 mg/L), followed by inhaled albuterol (2 puffs via metered-dose inhaler [MDI]), followed by inhaled placebo (2 puffs via MDI); (2) or al placebo followed by ipratropium (2 puffs via MDI; 36 mu g), followe d by inhaled placebo; (3) oral theophylline, followed -by albuterol, f ollowed by ipratropium; or (4) oral placebo followed by two inhaled pl acebos. On study days, spirometry and heart rate were measured at time 0, 30 min, 60 min, and hourly for 6 h. The FEV(1) peak change (liters ) and (liter X hours) for the treatment groups were compared. Ipratrop ium was more effective than placebo (p=0.001 and p=0.0078, respectivel y). The combination of albuterol and theophylline was superior to ipra tropium alone (p=0.0001 and p=0.0001, respectively), and all three dru gs together were superior to the combination of albuterol and theophyl line (p=0.0373 and p=0.0289, respectively; one-sided test of hypothese s). Peak heart rates were significantly higher for treatment groups co mpared with placebo groups (p=0.0001). However, theophylline and albut erol and the combination of all three drugs resulted in greater peak h eart rates than did ipratropium alone (p=0.001). These data suggest th at for patients with stable COPD, combination therapy with ipratropium (two puffs), theophylline, and albuterol (two puffs) is superior to i pratropium alone or the combination of theophylline and albuterol.