Trial Outcomes & Findings for Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study (NCT NCT02261727)
NCT ID: NCT02261727
Last Updated: 2021-08-12
Results Overview
The total number of COPD exacerbations reported within 48 weeks
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1670 participants
Primary outcome timeframe
48 weeks observation; rate annualised
Results posted on
2021-08-12
Participant Flow
Participant milestones
| Measure |
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
|
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)
|
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
|
|---|---|---|---|
|
Overall Study
STARTED
|
568
|
554
|
548
|
|
Overall Study
COMPLETED
|
411
|
408
|
423
|
|
Overall Study
NOT COMPLETED
|
157
|
146
|
125
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study
Baseline characteristics by cohort
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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
n=1670 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Sex: Female, Male
Male
|
426 Participants
n=93 Participants
|
434 Participants
n=4 Participants
|
404 Participants
n=27 Participants
|
1264 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Continuous
|
63.9 years
STANDARD_DEVIATION 8.5 • n=93 Participants
|
64.4 years
STANDARD_DEVIATION 7.8 • n=4 Participants
|
64.9 years
STANDARD_DEVIATION 7.7 • n=27 Participants
|
64.4 years
STANDARD_DEVIATION 8.0 • n=483 Participants
|
|
Sex: Female, Male
Female
|
128 Participants
n=93 Participants
|
134 Participants
n=4 Participants
|
144 Participants
n=27 Participants
|
406 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
554 Participants
n=93 Participants
|
568 Participants
n=4 Participants
|
548 Participants
n=27 Participants
|
1670 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
China
|
554 participants
n=93 Participants
|
568 participants
n=4 Participants
|
548 participants
n=27 Participants
|
1670 participants
n=483 Participants
|
|
Current Smoker
|
98 Participants
n=93 Participants
|
121 Participants
n=4 Participants
|
113 Participants
n=27 Participants
|
332 Participants
n=483 Participants
|
|
Pack Years - Current Smoker
|
43.5 years
STANDARD_DEVIATION 27.1 • n=93 Participants
|
40.5 years
STANDARD_DEVIATION 22.3 • n=4 Participants
|
44.4 years
STANDARD_DEVIATION 22.7 • n=27 Participants
|
42.7 years
STANDARD_DEVIATION 23.9 • n=483 Participants
|
|
Spirometry - Pre bronchodilator Forced Expiratory Volume in one second (FEV1)
|
1.0 L/sec
STANDARD_DEVIATION 0.4 • n=93 Participants
|
1.0 L/sec
STANDARD_DEVIATION 0.4 • n=4 Participants
|
0.9 L/sec
STANDARD_DEVIATION 0.4 • n=27 Participants
|
1.0 L/sec
STANDARD_DEVIATION 0.4 • n=483 Participants
|
PRIMARY outcome
Timeframe: 48 weeks observation; rate annualisedThe total number of COPD exacerbations reported within 48 weeks
Outcome measures
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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 COPD Exacerbation Rate
|
1.00 Exacerbations per participant year
Interval 0.87 to 1.14
|
0.86 Exacerbations per participant year
Interval 0.75 to 0.99
|
0.89 Exacerbations per participant year
Interval 0.78 to 1.02
|
SECONDARY outcome
Timeframe: Median time (days) from randomisation to first exacerbation over a 48 week period per participantThe median time (days) from randomisation to first exacerbation per participant
Outcome measures
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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
|
|---|---|---|---|
|
Time to First COPD Exacerbation
|
137 Days
Interval 58.5 to 233.5
|
150 Days
Interval 66.0 to 242.0
|
151 Days
Interval 71.0 to 247.0
|
SECONDARY outcome
Timeframe: Change over 48 week study durationTHe 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.
Outcome measures
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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
|
|---|---|---|---|
|
Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)
|
-4.95 Scores on a scale
Standard Deviation 0.91
|
-6.85 Scores on a scale
Standard Deviation 0.91
|
-6.48 Scores on a scale
Standard Deviation 0.89
|
SECONDARY outcome
Timeframe: Change at 48 weeksThe change in post bronchodilator FEV1 from baseline to 48 weeks
Outcome measures
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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
|
|---|---|---|---|
|
Post Bronchodilator FEV1
|
-0.02 L/sec
Standard Deviation 0.01
|
-0.01 L/sec
Standard Deviation 0.01
|
-0.02 L/sec
Standard Deviation 0.01
|
SECONDARY outcome
Timeframe: 48 weeksThe 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.
Outcome measures
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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
|
|---|---|---|---|
|
Change in COPD Assessment Test (CAT) Score
|
-2.29 Score on a scale
Standard Deviation 0.33
|
-2.77 Score on a scale
Standard Deviation 0.33
|
-2.57 Score on a scale
Standard Deviation 0.33
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 48 weeksThe total number of hospitalisation events within 48 weeks
Outcome measures
| Measure |
Placebo
n=554 Participants
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)
|
Low-dose Theophylline Arm
n=568 Participants
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 and Prednisone Arm
n=548 Participants
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
|
|---|---|---|---|
|
Hospitalisations
|
120 Number of hospitalisation events
|
101 Number of hospitalisation events
|
122 Number of hospitalisation events
|
Adverse Events
Placebo
Serious events: 96 serious events
Other events: 196 other events
Deaths: 3 deaths
Low-dose Theophylline Arm
Serious events: 91 serious events
Other events: 222 other events
Deaths: 2 deaths
Theophylline and Prednisone Arm
Serious events: 83 serious events
Other events: 202 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Placebo
n=554 participants at risk
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)
|
Low-dose Theophylline Arm
n=568 participants at risk
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 and Prednisone Arm
n=548 participants at risk
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
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation - Hospitalised
|
17.3%
96/554 • Number of events 135 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
16.0%
91/568 • Number of events 102 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
15.1%
83/548 • Number of events 115 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
Other adverse events
| Measure |
Placebo
n=554 participants at risk
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)
|
Low-dose Theophylline Arm
n=568 participants at risk
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 and Prednisone Arm
n=548 participants at risk
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
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation - not hospitalised
|
30.3%
168/554 • Number of events 306 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
31.9%
181/568 • Number of events 290 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
31.6%
173/548 • Number of events 306 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection
|
5.1%
28/554 • Number of events 37 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
7.2%
41/568 • Number of events 54 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
5.3%
29/548 • Number of events 34 • Adverse events were collected from all participants over the 48 weeks of the intervention period.
|
Additional Information
Prof Christine Jenkins
The George Institute for Global Health
Phone: +61280524300
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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".
- Publication restrictions are in place
Restriction type: OTHER