Low-dose theophylline in mild to moderate Chronic Obstructive Pulmonary Disease: A randomized clinical trial in China

Background Low-dose theophylline has anti-inflammatory effects, but its efficacy in mild to moderate COPD remains controversial.Research Question Is low dose theophylline effective and safe in patients with mild to moderate COPD?Methods In this prospective, parallel-group, randomised, double-blind, placebo-controlled trial across ten centres in China, subjects with mild to moderate COPD were randomized 2:1 to oral low-dose theophylline sustained-release tablets (100 mg twice daily) or matching placebo for 12 months. Primary endpoints were between-group differences in pre-bronchodilator FEV1 change from baseline to 12 months and annual exacerbation rate.Findings 734 subjects were randomized; 615 completed the study. Compared with placebo, low-dose theophylline significantly ameliorated FEV1 before bronchodilator use by 30 ml [95% CI, 3 to 57 ml] (p = 0.031) at month 12, with a between-group difference in mean change from baseline of 28 ml/year [95% CI, −2 to 58 ml/year] (p = 0.063). The annual exacerbation rate did not differ between groups (0.46 ± 0.03 vs 0.43 ± 0.04 per patient-year; RR, 1.07 [95% CI, 0.84 to 1.36]; p = 0.607). In addition, the incidence of adverse events was comparable between both groups.Interpretation In mild to moderate COPD, low-dose theophylline was well-tolerated but did not reduce exacerbation rates. A modest improvement in pre-bronchodilator FEV1 was observed, though its magnitude was limited. Larger trials are needed to further evaluate its potential to improve lung function in this population.