The Effect of Low Dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD. The TASCS Randomised Controlled Trial

The highest burden of Chronic Obstructive Pulmonary Disease (COPD) occurs in low and middle income countries. Low cost oral medications, if effective, could enable affordable, accessible COPD treatment. In this randomised, 3 arm, double-blind, double dummy, placebo controlled study conducted in 37 centres in China, symptomatic patients with moderate/very severe COPD were randomised 1:1:1 to low dose (LD) theophylline 100 mg bd+prednisone 5 mg once daily; LD theophylline 100 mg bd+placebo once daily; or placebo bd+placebo once daily for 48 weeks. The primary endpoint was annualised exacerbation rate. 1670 subjects were randomised, and 1242 completed the study (1142 with acceptable Week 48 data). Subjects (75.7% male) were mean age 64.4 years, with mean (sd) baseline post-bronchodilator Forced Expiratory Volume in 1 s (FEV ) 1.1 (0.4)L, 42.2% predicted and mean (sd) St Georges Respiratory Questionnaire (SGRQ) score 45.8 (20.1). There were negligible differences between annualised exacerbation rates across the three treatments, being 0.89 (95%CI=0.78-1.02) on Prednisone-LD Theophylline; 0.86 (0.75-0.99) on LD Theophylline plus placebo, and 1.00 (0.87-1.14) on double placebo. The Rate Ratio between the first and the pooled comparative arms was 0.96 (0.83-1.12), and for LD Theophylline+placebo placebo was 0.866, 95% CI 0.728; 1.029, p=0.101 and for LD Theophylline+Low dose oral Prednisone placebo was 0.895, 95% CI 0.755; 1.061, p=0.201. Secondary outcomes of hospitalisations, FEV , SGRQ and COPD Assessment Test (CAT) score showed no statistically significant difference between treatment arms. Serious adverse events (SAEs) other than exacerbations were