The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,670
- 试验地点
- 1
- 主要终点
- Total COPD Exacerbation Rate
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
- •Random blood glucose level > 8mmol/L
- •High chance in the view of the treating physician that the patient will not adhere to study treatment and follow up
研究组 & 干预措施
Placebo
Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
干预措施: Placebo (for prednisone) (Drug)
Placebo
Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
干预措施: Placebo (for Theophylline) (Drug)
Low-dose theophylline arm
Theophylline 100 mg twice daily
干预措施: Theophylline (Drug)
Low-dose theophylline arm
Theophylline 100 mg twice daily
干预措施: Placebo (for prednisone) (Drug)
Theophylline and Prednisone arm
Theophylline 100 mg twice daily plus prednisone 5 mg once daily
干预措施: Theophylline (Drug)
Theophylline and Prednisone arm
Theophylline 100 mg twice daily plus prednisone 5 mg once daily
干预措施: Prednisone (Drug)
结局指标
主要结局
Total COPD Exacerbation Rate
时间窗: 48 weeks observation; rate annualised
The total number of COPD exacerbations reported within 48 weeks
次要结局
- 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)