A comparison of inhaled ipratropium, oral theophylline plus inhaled beta-agonist, and the combination of all three in patients with COPD.

To evaluate the role of inhaled ipratropium bromide alone vs oral theophylline plus inhaled beta-agonist or the combination of all three in patients with stable COPD, the following double-blind, placebo-controlled study was conducted. Forty-eight patients with stable COPD (mean age, 61.8 years, with mean baseline FEV1 < 1.0 L) were randomized on four separate days to receive the following drug regimens: (1) theophylline tablets (dose previously determined to result in blood level of 12 to 18 mg/L), followed by inhaled albuterol (2 puffs via metered-dose inhaler [MDI]), followed by inhaled placebo (2 puffs via MDI); (2) oral placebo followed by ipratropium (2 puffs via MDI; 36 micrograms), followed by inhaled placebo; (3) oral theophylline, followed by albuterol, followed by ipratropium; or (4) oral placebo followed by two inhaled placebos. On study days, spirometry and heart rate were measured at time 0, 30 min, 60 min, and hourly for 6 h. The FEV1 peak change (liters) and area under the curve (liter x hours) for the treatment groups were compared. Ipratropium was more effective than placebo (p = 0.001 and p = 0.0078, respectively). The combination of albuterol and theophylline was superior to ipratropium alone (p = 0.001 and p = 0.0001, respectively), and all three drugs together were superior to the combination of albuterol and theophylline (p = 0.0373 and p = 0.0289), respectively; one-sided test of hypotheses). Peak heart rates were significantly higher for treatment groups compared with placebo groups (p = 0.0001). However, theophylline and albuterol and the combination of all three drugs resulted in greater peak heart rates than did ipratropium alone (p = 0.001). These data suggest that for patients with stable COPD, combination therapy with ipratropium (two puffs), theophylline, and albuterol (two puffs) is superior to ipratropium alone or the combination of theophylline and albuterol.