Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study

Chronic Obstructive Pulmonary Disease Clinical Trial

— TASCS  

Official title:

The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02261727
• Other study ID #: TGI-Resp-01
• Secondary ID: 1033117
• Status: Completed
• Phase: Phase 4
• Start date: June 2014
• Est. completion date: May 14, 2018

Study information

• Verified date: August 2021
• Source: The George Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1670
• Est. completion date: May 14, 2018
• Est. primary completion date: May 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Theophylline
Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor
• Prednisone
Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties
• Placebo (for prednisone)
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
• Placebo (for Theophylline)
One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)

Locations

Country	Name	City	State
Australia	The George Institute for Global Health	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
The George Institute	National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospitalisations	The total number of hospitalisation events within 48 weeks	48 weeks
Primary	Total COPD Exacerbation Rate	The total number of COPD exacerbations reported within 48 weeks	48 weeks observation; rate annualised
Secondary	Time to First COPD Exacerbation	The median time (days) from randomisation to first exacerbation per participant	Median time (days) from randomisation to first exacerbation over a 48 week period per participant
Secondary	Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)	THe St. George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.	Change over 48 week study duration
Secondary	Post Bronchodilator FEV1	The change in post bronchodilator FEV1 from baseline to 48 weeks	Change at 48 weeks
Secondary	Change in COPD Assessment Test (CAT) Score	The COPD Assessment Test (CAT) is a patient-completed questionnaire assessing globally the impact of COPD (cough, sputum, dysnea, chest tighteness) on health status. The range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. The outcome measure is assessing the change in score from baseline to 48 weeks. A negative change denotes an improvement in health status.	48 weeks