Clinical Trial Results:
Effects of ROFLUMILAST on markers of subclinical atherosclerosis In stable COPD; the ELASTIC-trial
Summary
|
|
EudraCT number |
2011-004152-19 |
Trial protocol |
AT |
Global end of trial date |
18 Jan 2016
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
12 Feb 2018
|
First version publication date |
12 Feb 2018
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
ELASTIC2011
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01630200 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology
|
||
Sponsor organisation address |
Sanatoriumstrasse 2, Vienna, Austria, 1140
|
||
Public contact |
Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, 0043 019106041007, matthias.urban@wienkav.at
|
||
Scientific contact |
Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, 0043 019106041007, matthias.urban@wienkav.at
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
24 Jul 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
18 Jan 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Jan 2016
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To investigate the effects of ROFLUMILAST 500µg once daily on arterial stiffness in patients with COPD
|
||
Protection of trial subjects |
Blood samples were taken at visit2 and 4 to rule a potential impairment of liver - or renal function
During 6 minute walk test dyspnea scores were assessed to quantify patients subjective amount of dyspnea and excertion
|
||
Background therapy |
not applicable | ||
Evidence for comparator |
not applicable | ||
Actual start date of recruitment |
02 Apr 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Austria: 80
|
||
Worldwide total number of subjects |
80
|
||
EEA total number of subjects |
80
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
40
|
||
From 65 to 84 years |
40
|
||
85 years and over |
0
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
Patients were recruited from an outpatient database of the Department of Respiratory and Critical Care Medicine in the Otto Wagner Hospital in Vienna. Recruitement started in April 2012 and lasted until July 2015. | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
A total of 240 patients were assessed for eligibility. Patients went through a 4 weeks run-in period to check for medication compliance. The primary reason for screening failure were comorbid diseases consistent with a predefined exclusion criteria. 80 patients were randomized to the study groups. | ||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
overall trial (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||||||||
Blinding implementation details |
The study was conducted in a double-blinded manner. All responsible persons, those administering the interventions or assessing the outcomes, and elementally all experimental and control patients were blinded to group assignment.
|
||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
Roflumilast arm | ||||||||||||||||||||||||
Arm description |
After Randomization patients from the Roflumilast arm received the study medication (IMP: Roflumilast, 500µg, once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Roflumilast arm were equivalent to the Placebo arm. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Roflumilast
|
||||||||||||||||||||||||
Investigational medicinal product code |
R03DX07
|
||||||||||||||||||||||||
Other name |
Daxas® (EU), Daliresp® (USA)
|
||||||||||||||||||||||||
Pharmaceutical forms |
Coated tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
500µg triangular coated tablet, administered oral once daily, in the morning
|
||||||||||||||||||||||||
Arm title
|
Placebo arm | ||||||||||||||||||||||||
Arm description |
After Randomization patients from the Placebo arm received Placebo (once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Placebo arm were equivalent to the Placebo arm. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
not applicable
|
||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Coated tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
500µg triangular coated tablet, administered oral once daily, in the morning
|
||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Roflumilast arm
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
After Randomization patients from the Roflumilast arm received the study medication (IMP: Roflumilast, 500µg, once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Roflumilast arm were equivalent to the Placebo arm. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo arm
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
After Randomization patients from the Placebo arm received Placebo (once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Placebo arm were equivalent to the Placebo arm. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Roflumilast arm
|
||
Reporting group description |
After Randomization patients from the Roflumilast arm received the study medication (IMP: Roflumilast, 500µg, once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Roflumilast arm were equivalent to the Placebo arm. | ||
Reporting group title |
Placebo arm
|
||
Reporting group description |
After Randomization patients from the Placebo arm received Placebo (once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Placebo arm were equivalent to the Placebo arm. |
|
|||||||||||||
End point title |
Change in Pulse Wave Velocity between Baseline and Final Visit | ||||||||||||
End point description |
Difference in the change of log Pulse Wave Velocity between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Measurement of Pulse Wave Velocity was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of primary endpoint | ||||||||||||
Statistical analysis description |
Primary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of cf-PWV from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of cf-PWV the analysis were calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 5 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
change from baseline RHI | ||||||||||||
End point description |
Difference in the change of Reactive Hyperemia Index between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Reactive Hyperemia Index was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of RHI from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of RHI the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
change from baseline AIx | ||||||||||||
End point description |
Difference in the change of Augmentation Index between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Augmentation Index was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of AIx from final visit for baseline as well as for GOLD stage. Due to a normal distribution of AIx the analysis was calculated unlogarythmised, resulting in an absolute difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline MMP-9 | ||||||||||||
End point description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of MMP-9 from final visit for baseline as well as for GOLD stage. Due to a normal distribution of AIx the analysis was calculated unlogarythmised, resulting in an absolute difference.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Matrix Metalloproteinase-9 was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of MMP-9 from final visit for baseline as well as for GOLD stage. Due to a normal distribution of MMP-9 the analysis was calculated unlogarythmised, resulting in an absolute difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline ADMA | ||||||||||||
End point description |
Difference in the change of Asymmetric Dimethyarginine between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Asymmetric Dimethyarginine was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of ADMA from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of ADMA the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline TNF-alpha | ||||||||||||
End point description |
Difference in the change of Tumor Necrosis Factor-alpha between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Tumor Necrosis Factor-alpha was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of TNF-alpha from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of TNF-alpha the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline IL-6 | ||||||||||||
End point description |
Difference in the change of Interleukin-6 between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Interleukin-6 was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of IL-6 from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of IL-6 the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline CRP | ||||||||||||
End point description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of CRP from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of CRP the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of C-reactive Protein was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of CRP from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of CRP the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline FEV1 | ||||||||||||
End point description |
Difference in the change of FEV1 between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of Forced Espiratory Volume in 1 Seocnd was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of FEV1 from final visit for baseline as well as for GOLD stage. Due to a right-skewed distribution of FEV1 the analysis was calculated under a log-scale, resulting in percentage difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline 6MWT | ||||||||||||
End point description |
Difference in the change of 6-Minute Walk Test between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of 6-Minute Walk Test was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Change from baseline 6MWT | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of 6MWT from final visit for baseline as well as for GOLD stage. Due to a normal distribution of 6MWT the analysis was calculated unlogarythmised, resulting in an absolute difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change from baseline CAT | ||||||||||||
End point description |
Difference in the change of CAT between the study groups (Roflumilast versus Placebo) after the 24 weeks study period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measurement of COPD Assessment Test was conducted firstly at the intial visit (following randomisation) and secondly after a study period of 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Intergroup comparison of secondary endpoint | ||||||||||||
Statistical analysis description |
Secondary endpoint was calculated via analysis of covariance (ANCOVA) with adjustment of the intergroup comparison of CAT from final visit for baseline as well as for GOLD stage. Due to a normal distribution of CAT the analysis was calculated unlogarythmised, resulting in an absolute difference.
|
||||||||||||
Comparison groups |
Roflumilast arm v Placebo arm
|
||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were reported during the 24 weeks active study phase starting with randomization and ending with the final visit.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events were collected routinely during every study visit. Moreover, patients were instructed to appraise the study team about potential adverse events intermittently via phone calls.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Roflumilast arm
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
After Randomization patients from the Roflumilast arm received the study medication (IMP: Roflumilast, 500µg, once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Roflumilast arm were equivalent to the Placebo arm. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo arm
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
After Randomization patients from the Placebo arm received Placebo (once daily, oral administration) in a double-blinded manner for a period of 24 weeks. Apart from the study medication, study related procedures in Placebo arm were equivalent to the Placebo arm. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |