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

• Sponsor: The George Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02261727
• Collaborator: National Health and Medical Research Council, Australia (Other)
• Enrollment: 1,670
• Location: 1
• Arms: 3
• Actual Duration (Months): 47.4
• Patients Per Site Per Month: 35.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Theophylline; Drug: Prednisone; Drug: Placebo (for prednisone); Drug: Placebo (for Theophylline)	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 1670 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial
• Actual Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: May 14, 2018
• Actual Study Completion Date: May 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily	Drug: 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; Other Names: Prednisone placebo 1 tab once daily in arms 1 and 2 ; Drug: Placebo (for Theophylline); One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily); Other Names: Theophylline placebo 1 tab twice daily
Active Comparator: Low-dose theophylline arm Theophylline 100 mg twice daily	Drug: Theophylline; Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor; Other Names: Theophylline (100 mg twice a day) ; Drug: 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; Other Names: Prednisone placebo 1 tab once daily in arms 1 and 2
Active Comparator: Theophylline and Prednisone arm Theophylline 100 mg twice daily plus prednisone 5 mg once daily	Drug: Theophylline; Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor; Other Names: Theophylline (100 mg twice a day) ; Drug: Prednisone; Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties; Other Names: Prednisone (5mg once daily) cortisone

Outcome Measures

Primary Outcome Measures

1. Total COPD Exacerbation Rate [48 weeks observation; rate annualised]

   The total number of COPD exacerbations reported within 48 weeks

Secondary Outcome Measures

1. Time to First COPD Exacerbation [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

2. Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ) [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.

3. Post Bronchodilator FEV1 [Change at 48 weeks]

   The change in post bronchodilator FEV1 from baseline to 48 weeks

4. Change in COPD Assessment Test (CAT) Score [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.

Other Outcome Measures

1. Hospitalisations [48 weeks]

   The total number of hospitalisation events within 48 weeks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The George Institute for Global Health	Sydney	New South Wales	Australia	2000

Sponsors and Collaborators

• The George Institute
• National Health and Medical Research Council, Australia

Investigators

• Principal Investigator: Norbert Berend, MD, The George Institute
• Principal Investigator: Christine R Jenkins, MD, The George Institute

Study Documents (Full-Text)

• Study Protocol - May 27, 2015
• Statistical Analysis Plan - Sep 14, 2018

More Information

Publications

None provided.

• Responsible Party: The George Institute
• ClinicalTrials.gov Identifier: NCT02261727
• Other Study ID Numbers: TGI-Resp-01; 1033117
• First Posted: Oct 10, 2014
• Last Update Posted: Aug 12, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by The George Institute: COPD; Theophylline; Oral corticosteroids; COPD exacerbations
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Prednisone; Cortisone; Theophylline

Study Results

Participant Flow

Arm/Group Title	Low-dose Theophylline Arm	Placebo	Theophylline and Prednisone Arm
Arm/Group Description	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	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)	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
Period Title: Overall Study
STARTED	568	554	548
COMPLETED	411	408	423
NOT COMPLETED	157	146	125

Baseline Characteristics

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm	Total
Arm/Group Description	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)	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	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	Total of all reporting groups
Overall Participants	554	568	548	1670
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (8.5)	64.4 (7.8)	64.9 (7.7)	64.4 (8.0)
Sex: Female, Male (Count of Participants)
Female	128 23.1%	134 23.6%	144 26.3%	406 24.3%
Male	426 76.9%	434 76.4%	404 73.7%	1264 75.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	554 100%	568 100%	548 100%	1670 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	554 100%	568 100%	548 100%	1670 100%
Current Smoker (Count of Participants)
Count of Participants [Participants]	98 17.7%	121 21.3%	113 20.6%	332 19.9%
Pack Years - Current Smoker (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.5 (27.1)	40.5 (22.3)	44.4 (22.7)	42.7 (23.9)
Spirometry - Pre bronchodilator Forced Expiratory Volume in one second (FEV1) (L/sec) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [L/sec]	1.0 (0.4)	1.0 (0.4)	0.9 (0.4)	1.0 (0.4)

Outcome Measures

1. Primary Outcome

Title	Total COPD Exacerbation Rate
Description	The total number of COPD exacerbations reported within 48 weeks
Time Frame	48 weeks observation; rate annualised

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm
Arm/Group Description	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)	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	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
Measure Participants	554	568	548
Number (95% Confidence Interval) [Exacerbations per participant year]	1.00	0.86	0.89

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm
Arm/Group Description	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)	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	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
Measure Participants	554	568	548
Median (Inter-Quartile Range) [Days]	137	150	151

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm
Arm/Group Description	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)	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	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
Measure Participants	554	568	548
Mean (Standard Deviation) [Scores on a scale]	-4.95 (0.91)	-6.85 (0.91)	-6.48 (0.89)

4. Secondary Outcome

Title	Post Bronchodilator FEV1
Description	The change in post bronchodilator FEV1 from baseline to 48 weeks
Time Frame	Change at 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm
Arm/Group Description	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)	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	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
Measure Participants	554	568	548
Mean (Standard Deviation) [L/sec]	-0.02 (0.01)	-0.01 (0.01)	-0.02 (0.01)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm
Arm/Group Description	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)	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	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
Measure Participants	554	568	548
Mean (Standard Deviation) [Score on a scale]	-2.29 (0.33)	-2.77 (0.33)	-2.57 (0.33)

6. Other Pre-specified Outcome

Title	Hospitalisations
Description	The total number of hospitalisation events within 48 weeks
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Low-dose Theophylline Arm	Theophylline and Prednisone Arm
Arm/Group Description	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)	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	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
Measure Participants	554	568	548
Number [Number of hospitalisation events]	120	101	122

Adverse Events

Time Frame	Adverse events were collected from all participants over the 48 weeks of the intervention period.
Arm/Group Title	Placebo		Low-dose Theophylline Arm		Theophylline and Prednisone Arm
Arm/Group Description	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)		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		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
All Cause Mortality
	Placebo		Low-dose Theophylline Arm		Theophylline and Prednisone Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/554 (0.5%)		2/568 (0.4%)		2/548 (0.4%)
Serious Adverse Events
	Placebo		Low-dose Theophylline Arm		Theophylline and Prednisone Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/554 (17.3%)		91/568 (16%)		83/548 (15.1%)
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation - Hospitalised	96/554 (17.3%)	135	91/568 (16%)	102	83/548 (15.1%)	115
Other (Not Including Serious) Adverse Events
	Placebo		Low-dose Theophylline Arm		Theophylline and Prednisone Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	196/554 (35.4%)		222/568 (39.1%)		202/548 (36.9%)
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation - not hospitalised	168/554 (30.3%)	306	181/568 (31.9%)	290	173/548 (31.6%)	306
Upper Respiratory Tract Infection	28/554 (5.1%)	37	41/568 (7.2%)	54	29/548 (5.3%)	34

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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".