Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Theophylline; Prednisone; Placebo (for prednisone); Placebo (for Theophylline)
Intervention description: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor; Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties; Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily
Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily; One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)
Intervention MeSH terms: Prednisone; Cortisone; Theophylline
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 1670.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COPD; Theophylline; Oral corticosteroids; COPD exacerbations

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.
    

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)

          -  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