Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study (TASCS)
August 10, 2021 updated by: The George Institute
The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Study Type
Interventional
Enrollment (Actual)
1670
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New South Wales
-
Sydney, New South Wales, Australia, 2000
- The George Institute for Global Health
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
|
Other Names:
One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)
Other Names:
|
|
Active Comparator: Low-dose theophylline arm
Theophylline 100 mg twice daily
|
Other Names:
Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor
Other Names:
|
|
Active Comparator: Theophylline and Prednisone arm
Theophylline 100 mg twice daily plus prednisone 5 mg once daily
|
Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor
Other Names:
Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Total COPD Exacerbation Rate
Time Frame: 48 weeks observation; rate annualised
|
The total number of COPD exacerbations reported within 48 weeks
|
48 weeks observation; rate annualised
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to First COPD Exacerbation
Time Frame: Median time (days) from randomisation to first exacerbation over a 48 week period per participant
|
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
|
|
Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)
Time Frame: Change over 48 week study duration
|
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
|
|
Post Bronchodilator FEV1
Time Frame: Change at 48 weeks
|
The change in post bronchodilator FEV1 from baseline to 48 weeks
|
Change at 48 weeks
|
|
Change in COPD Assessment Test (CAT) Score
Time Frame: 48 weeks
|
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
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Hospitalisations
Time Frame: 48 weeks
|
The total number of hospitalisation events within 48 weeks
|
48 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Norbert Berend, MD, The George Institute
- Principal Investigator: Christine R Jenkins, MD, The George Institute
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2014
Primary Completion (Actual)
May 14, 2018
Study Completion (Actual)
May 14, 2018
Study Registration Dates
First Submitted
May 7, 2014
First Submitted That Met QC Criteria
October 9, 2014
First Posted (Estimate)
October 10, 2014
Study Record Updates
Last Update Posted (Actual)
August 12, 2021
Last Update Submitted That Met QC Criteria
August 10, 2021
Last Verified
August 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Purinergic Antagonists
- Purinergic Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Theophylline
- Prednisone
- Cortisone
Other Study ID Numbers
- TGI-Resp-01
- 1033117 (Other Grant/Funding Number: National Health and Medical Research Council, Australia)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.