Clinical trial NCT02261727: Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study
Official title: The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Theophylline
Oral corticosteroids
COPD exacerbations
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
First posted: 2014-10-10
Enrollment: 1670
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Total COPD Exacerbation Rate
timeFrame: 48 weeks observation; rate annualised
Secondary outcomes:
measure: Time to First COPD Exacerbation
timeFrame: Median time (days) from randomisation to first exacerbation over a 48 week period per participant
measure: Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)
timeFrame: Change over 48 week study duration
measure: Post Bronchodilator FEV1
timeFrame: Change at 48 weeks
measure: Change in COPD Assessment Test (CAT) Score
timeFrame: 48 weeks
Other outcomes:
measure: Hospitalisations
timeFrame: 48 weeks
Locations:
city: Sydney
country: Australia
facility: The George Institute for Global Health
state: New South Wales
Study officials:
affiliation: The George Institute
name: Norbert Berend, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The George Institute
name: Christine R Jenkins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jenkins CR, Wen FQ, Martin A, Barnes PJ, Celli B, Zhong NS, Zheng JP, Scaria A, Di Tanna GL, Bradbury T, Berend N; TASCS study investigators. The effect of low-dose corticosteroids and theophylline on the risk of acute exacerbations of COPD: the TASCS randomised controlled trial. Eur Respir J. 2021 Jun 10;57(6):2003338. doi: 10.1183/13993003.03338-2020. Print 2021 Jun.