Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1033117 | Other Grant/Funding Number | National Health and Medical Research Council, Australia |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Health and Medical Research Council, Australia | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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:
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily |
|
| Low-dose theophylline arm | Active Comparator | Theophylline 100 mg twice daily |
|
| Theophylline and Prednisone arm | Active Comparator | Theophylline 100 mg twice daily plus prednisone 5 mg once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Theophylline | Drug | Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Total COPD Exacerbation Rate | The total number of COPD exacerbations reported within 48 weeks | 48 weeks observation; rate annualised |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ) |
| Measure | Description | Time Frame |
|---|---|---|
| Hospitalisations | The total number of hospitalisation events within 48 weeks | 48 weeks |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Norbert Berend, MD | The George Institute | Principal Investigator |
| Christine R Jenkins, MD | The George Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The George Institute for Global Health | Sydney | New South Wales | 2000 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33334939 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Low-dose Theophylline Arm | Theophylline 100 mg twice daily Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor 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 |
| FG001 | Placebo | Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily 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 twice daily + prednisone placebo 1 once daily) |
| FG002 | Theophylline and Prednisone Arm | Theophylline 100 mg twice daily plus prednisone 5 mg once daily 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total COPD Exacerbation Rate | The total number of COPD exacerbations reported within 48 weeks | Posted | Number | 95% Confidence Interval | Exacerbations per participant year | 48 weeks observation; rate annualised |
|
Adverse events were collected from all participants over the 48 weeks of the intervention period.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COPD Exacerbation - Hospitalised | Respiratory, thoracic and mediastinal disorders | MedDRA (1701) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COPD Exacerbation - not hospitalised | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
There are some limitations to our study, there was a 26% withdrawal rate in this study, with a higher rate of withdrawals occurring earlier in the trial. Patients requested withdrawal if they felt the treatment was not helping them and, in particular, if they suffered an exacerbation. This was most evident at the first study visit after treatment commencement, when the greatest number of withdrawals occurred.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof Christine Jenkins | The George Institute for Global Health | +61280524300 | christine.jenkins@sydney.edu.au |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 27, 2015 | Jun 20, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 14, 2018 | Jun 20, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| D013806 | Theophylline |
| D011241 | Prednisone |
| D003348 | Cortisone |
| ID | Term |
|---|---|
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D011688 | Purinones |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Prednisone | Drug | Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties |
|
|
| Placebo (for prednisone) | Drug |
|
|
|
| Placebo (for Theophylline) | Drug | One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily) |
|
|
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 | The change in post bronchodilator FEV1 from baseline to 48 weeks | Change at 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. | 48 weeks |
| BG001 | Low-dose Theophylline Arm | Theophylline 100 mg twice daily Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor 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 |
| BG002 | Theophylline and Prednisone Arm | Theophylline 100 mg twice daily plus prednisone 5 mg once daily 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Current Smoker | Count of Participants | Participants |
|
| Pack Years - Current Smoker | Mean | Standard Deviation | years |
|
| Spirometry - Pre bronchodilator Forced Expiratory Volume in one second (FEV1) | Mean | Standard Deviation | L/sec |
|
| OG002 | Theophylline and Prednisone Arm | Theophylline 100 mg twice daily plus prednisone 5 mg once daily 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 |
|
|
| Secondary | Time to First COPD Exacerbation | The median time (days) from randomisation to first exacerbation per participant | Posted | Median | Inter-Quartile Range | Days | 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. | Posted | Mean | Standard Deviation | Scores on a scale | Change over 48 week study duration |
|
|
|
| Secondary | Post Bronchodilator FEV1 | The change in post bronchodilator FEV1 from baseline to 48 weeks | Posted | Mean | Standard Deviation | L/sec | 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. | Posted | Mean | Standard Deviation | Score on a scale | 48 weeks |
|
|
|
| Other Pre-specified | Hospitalisations | The total number of hospitalisation events within 48 weeks | Posted | Number | Number of hospitalisation events | 48 weeks |
|
|
|
| 3 |
| 554 |
| 96 |
| 554 |
| 196 |
| 554 |
| EG001 | Low-dose Theophylline Arm | Theophylline 100 mg twice daily Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor 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 | 2 | 568 | 91 | 568 | 222 | 568 |
| EG002 | Theophylline and Prednisone Arm | Theophylline 100 mg twice daily plus prednisone 5 mg once daily 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 | 2 | 548 | 83 | 548 | 202 | 548 |
| Upper Respiratory Tract Infection | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
All papers will be authored by all or a subgroup of members of the TASCS Publications Committee. Publications prior to the primary and major secondary papers may only be initiated by the Publications Committee. Publications subsequent to the primary and major secondary papers may be authored by individually named authors, and may at the request of the Publication Committee be required to include the annotation "On behalf of the Theophylline and Steroids in COPD (TASCS) trial investigators".
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011687 |
| Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D011283 | Pregnenes |
| D015065 | 17-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |