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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Completed
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Theophylline
Prednisone
Placebo (for prednisone)
Placebo (for Theophylline)
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, Theophylline, Oral corticosteroids, COPD exacerbations

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The George Institute for Global Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo

Low-dose theophylline arm

Theophylline and Prednisone arm

Arm Description

Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily

Theophylline 100 mg twice daily

Theophylline 100 mg twice daily plus prednisone 5 mg once daily

Outcomes

Primary Outcome Measures

Total COPD Exacerbation Rate
The total number of COPD exacerbations reported within 48 weeks

Secondary Outcome Measures

Time to First COPD Exacerbation
The median time (days) from randomisation to first exacerbation per participant
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.
Post Bronchodilator FEV1
The change in post bronchodilator FEV1 from baseline to 48 weeks
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.

Full Information

First Posted
May 7, 2014
Last Updated
August 10, 2021
Sponsor
The George Institute
Collaborators
National Health and Medical Research Council, Australia
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1. Study Identification

Unique Protocol Identification Number
NCT02261727
Brief Title
Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study
Acronym
TASCS
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

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
June 2014 (Actual)
Primary Completion Date
May 14, 2018 (Actual)
Study Completion Date
May 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Institute
Collaborators
National Health and Medical Research Council, Australia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
COPD, Theophylline, Oral corticosteroids, COPD exacerbations

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1670 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
Arm Title
Low-dose theophylline arm
Arm Type
Active Comparator
Arm Description
Theophylline 100 mg twice daily
Arm Title
Theophylline and Prednisone arm
Arm Type
Active Comparator
Arm Description
Theophylline 100 mg twice daily plus prednisone 5 mg once daily
Intervention Type
Drug
Intervention Name(s)
Theophylline
Other Intervention Name(s)
Theophylline (100 mg twice a day)
Intervention Description
Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Prednisone (5mg once daily), cortisone
Intervention Description
Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties
Intervention Type
Drug
Intervention Name(s)
Placebo (for prednisone)
Other Intervention Name(s)
Prednisone placebo 1 tab once daily in arms 1 and 2
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo (for Theophylline)
Other Intervention Name(s)
Theophylline placebo 1 tab twice daily
Intervention Description
One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)
Primary Outcome Measure Information:
Title
Total COPD Exacerbation Rate
Description
The total number of COPD exacerbations reported within 48 weeks
Time Frame
48 weeks observation; rate annualised
Secondary Outcome Measure Information:
Title
Time to First COPD Exacerbation
Description
The median time (days) from randomisation to first exacerbation per participant
Time Frame
Median time (days) from randomisation to first exacerbation over a 48 week period per participant
Title
Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)
Description
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.
Time Frame
Change over 48 week study duration
Title
Post Bronchodilator FEV1
Description
The change in post bronchodilator FEV1 from baseline to 48 weeks
Time Frame
Change at 48 weeks
Title
Change in COPD Assessment Test (CAT) Score
Description
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.
Time Frame
48 weeks
Other Pre-specified Outcome Measures:
Title
Hospitalisations
Description
The total number of hospitalisation events within 48 weeks
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norbert Berend, MD
Organizational Affiliation
The George Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christine R Jenkins, MD
Organizational Affiliation
The George Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The George Institute for Global Health
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2000
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33334939
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.
Results Reference
derived

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

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