Clinical Trial Results:
Effect of theophylline on histone deacetylase activity: enhancement of in-vitro glucocorticoid function in patients with COPD.
Summary
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EudraCT number |
2005-003344-62 |
Trial protocol |
GB |
Global end of trial date |
29 Aug 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Nov 2019
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First version publication date |
13 Nov 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
mitHDAC
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00241631 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
South Kensingston Campus, London, United Kingdom, SW7 2AZ
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Public contact |
Prof Ian Adcock, Imperial College London, +44 20 7594 7840, ian.adcock@imperial.ac.uk
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Scientific contact |
Prof Ian Adcock, Imperial College London, +44 20 7594 7840, ian.adcock@imperial.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Aug 2008
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Aug 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Aug 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Does the addition of low dose theophylline (a drug already commonly used in Chronic Obstructive Lung Disease - COPD) restore the putative anti-inflammatory effects (measured from in-vitro samples taken by inducing sputum production) of inhaled steroids in patients with COPD?
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Protection of trial subjects |
None
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Apr 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 49
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Worldwide total number of subjects |
49
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EEA total number of subjects |
49
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
30
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From 65 to 84 years |
19
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited between April 2006 and August 2007. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Total of Forty-nine theophylline-naive (Global Initiative for Chronic Obstructive Lung Disease stage 2 or 3) patients with COPD were screened, 30 participants completed the study. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Run-in
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Is this the baseline period? |
No | ||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Arm title
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All participants | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 2
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Period 2 title |
Phase 1
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Is this the baseline period? |
No | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Inhaled placebo capsule | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour, tablet
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Routes of administration |
Inhalation use
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Dosage and administration details |
4 weeks
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
placebo theophylline capsules for 4 weeks
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Arm title
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Steroid | ||||||||||||||||||||||||
Arm description |
Inhaled Theophylline placebo capsule, then Fluticasone Propionate 500 ug bid, then active Theophylline | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Fluticasone Propionate
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Investigational medicinal product code |
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Other name |
Flovent
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Pharmaceutical forms |
Inhalation vapour, capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
500 ug bid for 4 weeks
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
placebo theophylline capsules
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Period 3
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Period 3 title |
Phase 2
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Is this the baseline period? |
Yes [1] | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Inhaled placebo plus oral slo-phylline capsule 250mg bid | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Theophylline
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Investigational medicinal product code |
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Other name |
Slo-phyllin capsule
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
250 mg bid for 4 weeks
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour, tablet
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Routes of administration |
Inhalation use
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Dosage and administration details |
4 weeks
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Arm title
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Steroid | ||||||||||||||||||||||||
Arm description |
Inhaled Fluticasomne propionate 500mg bid plus oral slo-phylline capsule 250mg bid | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Theophylline
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Investigational medicinal product code |
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Other name |
Slo-phyllin capsule
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
250 mg bid for 4 weeks
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Investigational medicinal product name |
Fluticasone Propionate
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Investigational medicinal product code |
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Other name |
Flovent
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Pharmaceutical forms |
Inhalation vapour, capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
500 ug bid for 4 weeks
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Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Baseline period we reported participants they completed the study |
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Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline period we reported participants they completed the study |
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Period 4
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Period 4 title |
Wash out
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Is this the baseline period? |
No | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Arm title
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All participants | ||||||||||||||||||||||||
Arm description |
All participants between phase 1 and 2, no treatment | ||||||||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Inhaled placebo plus oral slo-phylline capsule 250mg bid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Steroid
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Reporting group description |
Inhaled Fluticasomne propionate 500mg bid plus oral slo-phylline capsule 250mg bid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All participants
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
Inhaled placebo capsule | ||
Reporting group title |
Steroid
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Reporting group description |
Inhaled Theophylline placebo capsule, then Fluticasone Propionate 500 ug bid, then active Theophylline | ||
Reporting group title |
Placebo
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Reporting group description |
Inhaled placebo plus oral slo-phylline capsule 250mg bid | ||
Reporting group title |
Steroid
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Reporting group description |
Inhaled Fluticasomne propionate 500mg bid plus oral slo-phylline capsule 250mg bid | ||
Reporting group title |
All participants
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Reporting group description |
All participants between phase 1 and 2, no treatment |
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End point title |
Sputum Inflammatory Cell Counts | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
10 weeks
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Statistical analysis title |
Sputum Inflammatory Cell Counts | ||||||||||||
Comparison groups |
Placebo v Steroid
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Number of subjects included in analysis |
30
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.012 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Interleukin 8 (IL8) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
10 weeks
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Statistical analysis title |
IL 8 | ||||||||||||
Comparison groups |
Placebo v Steroid
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Number of subjects included in analysis |
30
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 [1] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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Notes [1] - calculated |
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End point title |
Total sputum eosinophils | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
10 weeks
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Statistical analysis title |
Total sputum eosinophils | ||||||||||||
Comparison groups |
Steroid v Placebo
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Number of subjects included in analysis |
30
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 [2] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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Notes [2] - calculated |
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Adverse events information
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Timeframe for reporting adverse events |
10 weeks
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Assessment type |
Non-systematic | ||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Inhaled Theophylline placebo capsule, then placebo, then active Theophylline | ||||||||||||||||||||||||
Reporting group title |
Steroid
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Reporting group description |
Inhaled Theophylline placebo capsule, then Fluticasone Propionate 500 ug bid, then active Theophylline | ||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/20299628 |