Abstract
Background 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.
Methods 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.
Findings 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 (FEV1) 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 versus placebo was 0.866, 95% CI 0.728; 1.029, p=0.101 and for LD Theophylline+Low dose oral Prednisone versus placebo was 0.895, 95% CI 0.755; 1.061, p=0.201. Secondary outcomes of hospitalisations, FEV1, SGRQ and COPD Assessment Test (CAT) score showed no statistically significant difference between treatment arms. Serious adverse events (SAEs) other than exacerbations were <2% and did not differ between the treatment arms.
Conclusions LD theophylline alone or in combination with prednisone did not reduce exacerbation rates or clinically important secondary endpoints compared to placebo.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Jenkins reports personal fees from Boehringer Ingelheim, grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Novartis, personal fees and non-financial support from Sanofi Genzyme, personal fees from Chiesi, outside the submitted work.
Conflict of interest: Dr. Wen has nothing to disclose.
Conflict of interest: Dr. Martin has nothing to disclose.
Conflict of interest: Dr. Barnes reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Pieris, personal fees from Epi-Endo, outside the submitted work.
Conflict of interest: Dr. Celli reports personal fees and other from Astra Zeneca, personal fees from GlaxoSmithKline, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Sanofi Aventis and personal fess form Menarini other from outside the submitted work.
Conflict of interest: Dr. Zhong has nothing to disclose.
Conflict of interest: Dr. Zheng has nothing to disclose.
Conflict of interest: Mr. Scaria has nothing to disclose.
Conflict of interest: Dr. Di Tanna reports personal fees from Amgen, outside the submitted work.
Conflict of interest: Mr. Bradbury reports receiving a top-up scholarship funded by GlaxoSmithKline, outside the submitted work.
Conflict of interest: Dr. Berend reports grants from NHMRC Australia, grants from State Key lab of respiratory Disease and Guanzhou institute of respiratory disease China, grants from West china Hospital, Chengdu, china, during the conduct of the study; other from Glaxo Smith Kline, outside the submitted work.
- Received September 1, 2020.
- Accepted November 21, 2020.
- Copyright ©ERS 2020
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