OBJECTIVE: To observe the benefits and safety of low-dose, slow-release oral theophylline for long-term treatment of stable chronic obstructive pulmonary disease (COPD). METHODS: This was a randomized, parallel-group, double-blind, placebo-controlled trial. Slow-release theophylline (200 mg/d) twice daily or placebo (matching theophylline) was randomly given to 110 patients with stable COPD in the rural area of Shaoguan, Guangdong Province, for one year. Efficacy measures were spirometry and exacerbations, quality of life, dyspnea scores, satisfaction with treatments and adverse effects. Comparison of benefits was performed using superiority test. RESULTS:Of 110 patients, 85 (42 subjects in theophylline group and 43 subjects in placebo group) completed the study. An analysis for intention-to-treat (ITT) individuals showed that individuals with the treatment of theophylline experienced statistically fewer numbers [(0.8 +/- 1.2) times/year, (1.7 +/- 2.6) times/year, Z = -1.674, P = 0.047] and days of exacerbations [(4.6 +/- 7.9) d, (12.5 +/- 22.8) d, Z = -1.699, P = 0.045] in comparison to subjects receiving placebo, that patients receiving theophylline were less likely than the placebo group to experience moderate exacerbations [(0.4 +/- 1.0) times/year, (1.0 +/- 1.8) times/year, Z = -2.136, P = 0.017], and that more individuals satisfied with treatments in the theophylline group than the placebo group (n = 16, 3, Z = -2.198, P = 0.014), and that statistically greater improvement in pre-bronchodilators FEV(1) [(0.006 +/- 0.180) L, (-0.053 +/- 0.169) L, t = 1.789, P = 0.038] were found in the theophylline group in comparison to the placebo group. The similar results were observed in an analysis for per-protocol (PP) subjects. Statistical improvement on quality of life was observed in the PP subjects of theophylline group than in placebo group (-28 +/- 20, -20 +/- 23, F = 2.893, P = 0.047). Time to the first exacerbation in patients receiving theophylline was also delayed in comparison to placebo (365 d, 276 d, chi(2) = 3.880, P = 0.049). But no statistical difference was found between the two groups in post-bronchodilators FEV(1) in both ITT and PP subjects (t = -0.012, P = 0.495 and t = 0.040, P = 0.484 respectively). Drug-related adverse events (8.8%) such as insomnia, palpitation, stomach discomforts or stomachache, and headache were observed in the theophylline group. CONCLUSION:Slow-released oral theophylline (200 mg/d) may be beneficial and safe in long-term treatment of stable COPD in rural area.
RCT Entities:
OBJECTIVE: To observe the benefits and safety of low-dose, slow-release oral theophylline for long-term treatment of stable chronic obstructive pulmonary disease (COPD). METHODS: This was a randomized, parallel-group, double-blind, placebo-controlled trial. Slow-release theophylline (200 mg/d) twice daily or placebo (matching theophylline) was randomly given to 110 patients with stable COPD in the rural area of Shaoguan, Guangdong Province, for one year. Efficacy measures were spirometry and exacerbations, quality of life, dyspnea scores, satisfaction with treatments and adverse effects. Comparison of benefits was performed using superiority test. RESULTS: Of 110 patients, 85 (42 subjects in theophylline group and 43 subjects in placebo group) completed the study. An analysis for intention-to-treat (ITT) individuals showed that individuals with the treatment of theophylline experienced statistically fewer numbers [(0.8 +/- 1.2) times/year, (1.7 +/- 2.6) times/year, Z = -1.674, P = 0.047] and days of exacerbations [(4.6 +/- 7.9) d, (12.5 +/- 22.8) d, Z = -1.699, P = 0.045] in comparison to subjects receiving placebo, that patients receiving theophylline were less likely than the placebo group to experience moderate exacerbations [(0.4 +/- 1.0) times/year, (1.0 +/- 1.8) times/year, Z = -2.136, P = 0.017], and that more individuals satisfied with treatments in the theophylline group than the placebo group (n = 16, 3, Z = -2.198, P = 0.014), and that statistically greater improvement in pre-bronchodilators FEV(1) [(0.006 +/- 0.180) L, (-0.053 +/- 0.169) L, t = 1.789, P = 0.038] were found in the theophylline group in comparison to the placebo group. The similar results were observed in an analysis for per-protocol (PP) subjects. Statistical improvement on quality of life was observed in the PP subjects of theophylline group than in placebo group (-28 +/- 20, -20 +/- 23, F = 2.893, P = 0.047). Time to the first exacerbation in patients receiving theophylline was also delayed in comparison to placebo (365 d, 276 d, chi(2) = 3.880, P = 0.049). But no statistical difference was found between the two groups in post-bronchodilators FEV(1) in both ITT and PP subjects (t = -0.012, P = 0.495 and t = 0.040, P = 0.484 respectively). Drug-related adverse events (8.8%) such as insomnia, palpitation, stomach discomforts or stomachache, and headache were observed in the theophylline group. CONCLUSION: Slow-released oral theophylline (200 mg/d) may be beneficial and safe in long-term treatment of stable COPD in rural area.