The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial
Overview
- Phase
- Phase 4
- Intervention
- Placebo (for prednisone)
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- The George Institute
- Enrollment
- 1670
- Locations
- 1
- Primary Endpoint
- Total COPD Exacerbation Rate
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The aim of this multi-centre, double blind, randomised, controlled trial (DBRCT) is to assess the effect of low dose theophylline, singly and in combination with low dose oral prednisone, on COPD (Chronic Obstructive Pulmonary Disease) exacerbations, quality of life and secondary clinical outcomes compared with usual therapy and placebo over 48 weeks of treatment. 1670 symptomatic patients with COPD will be recruited in China for comparison of low dose theophylline versus placebo and low dose theophylline + low dose prednisone The primary end-point for this study is the annualised COPD exacerbation rate between the treatment groups. Secondary outcomes included time to first severe exacerbation requiring hospitalisation or death, health status, and pre- and post-bronchodilator spirometry.
Detailed Description
The investigators hypothesise that patients with COPD will have beneficial responses to low dose theophylline and prednisone, superior to placebo and low dose theophylline alone, reflected by a range of clinical outcomes. The study aims to demonstrate that treatment with low dose oral prednisone and low dose, slow release theophylline compared to low dose, slow release theophylline only or placebo will reduce COPD exacerbations and improve a range of secondary outcomes including quality of life, COPD Assessment Test (CAT) score, hospital admissions and lung function. Eligible participants will be randomised to one of three treatment arms in a DBRCT and will receive placebo OR low-dose theophylline (100 mg twice a day) OR low-dose theophylline 100 mg twice a day (BD) plus low-dose prednisone (5 mg once a day) Patients will be eligible for inclusion if all the following criteria are met: * Current or former smokers (\>10 pack years) or biomass exposure * 40 - 80 years of age * Clinical diagnosis of COPD * Post-bronchodilator forced expiratory volume at one second (FEV1) \<70% predicted * Post bronchodilator FEV1/forced vital capacity (FVC) ratio\<0.7
Investigators
Eligibility Criteria
Inclusion Criteria
- •Current or former smokers (\> 10 pack years) or biomass exposure
- •40 - 80 years of age
- •Clinical diagnosis of COPD
- •Post-bronchodilator FEV1 \< 70% predicted
- •Post bronchodilator FEV1/FVC ratio \< 0.7
Exclusion Criteria
- •Life expectancy of less than 12 months
- •Exacerbation or respiratory infection within 4 weeks prior to randomisation
- •Patient is taking and requires maintenance oral corticosteroids
- •Patient is on domiciliary oxygen
- •There has been previous pulmonary resection
- •Previous sensitivity to, or intolerance of theophylline
- •Coexistent illness precluding participation in the study (epilepsy, chronic liver disease, unstable cardiovascular disease, diabetes, active malignancy)
- •Inability to complete quality of life questionnaire
- •Concomitant major illness that would interfere with visits, assessments and follow-up
- •Have evidence of chronic liver disease, or transaminase or gamma-glutamyltransferase (GGT) elevation \> 1.5 x upper limit of normal (ULN)
Arms & Interventions
Placebo
Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
Intervention: Placebo (for prednisone)
Placebo
Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
Intervention: Placebo (for Theophylline)
Low-dose theophylline arm
Theophylline 100 mg twice daily
Intervention: Theophylline
Low-dose theophylline arm
Theophylline 100 mg twice daily
Intervention: Placebo (for prednisone)
Theophylline and Prednisone arm
Theophylline 100 mg twice daily plus prednisone 5 mg once daily
Intervention: Theophylline
Theophylline and Prednisone arm
Theophylline 100 mg twice daily plus prednisone 5 mg once daily
Intervention: Prednisone
Outcomes
Primary Outcomes
Total COPD Exacerbation Rate
Time Frame: 48 weeks observation; rate annualised
The total number of COPD exacerbations reported within 48 weeks
Secondary Outcomes
- Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)(Change over 48 week study duration)
- Time to First COPD Exacerbation(Median time (days) from randomisation to first exacerbation over a 48 week period per participant)
- Post Bronchodilator FEV1(Change at 48 weeks)
- Change in COPD Assessment Test (CAT) Score(48 weeks)