Clinical Trial Results:
Pilot study to evaluate whether treating persistent small airway dysfunction with extra-fine HFA-Beclometasone results in improved asthma control.
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Summary
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EudraCT number |
2012-003923-39 |
Trial protocol |
GB |
Global end of trial date |
25 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Jun 2019
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First version publication date |
22 Jun 2019
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Other versions |
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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 |
2012RC16
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01894048 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Dundee - NHS Tayside
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Sponsor organisation address |
Residency Block, Level 3, Ninewells Hospital, George Pirie Way, Dundee, United Kingdom, DD1 9SY
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Public contact |
Professor Brian Lipworth, Scottish Centre for Respiratory Research, 44 01382 383188, b.j.lipworth@dundee.ac.uk
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Scientific contact |
Professor Brian Lipworth, Scottish Centre for Respiratory Research, 44 01382 383188, b.j.lipworth@dundee.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 |
25 Jun 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Jun 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jun 2018
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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 |
To assess patient reported outcomes after switching from large to small particle beclometasone dipropionate (BDP) in persistent asthma.
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Protection of trial subjects |
The study was approved by the East of Scotland Research Ethics Service (EoSRES).
Potential participants received a written Participant Information Sheet (PIS) detailing the requirements of the trial and the extent of their participation before attending for a screening visit. Participants were given at least 24 hours to read the PIS and were encouraged to discuss their potential study participation with others, such as their doctor, family or friends. At the study screening visit, a member of the research team discussed the PIS with the participant and answered any questions posed. Written informed consent was obtained prior to any study-specific procedures.
Participants were only selected if they fulfilled the pre-determined inclusion criteria.
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Background therapy |
Patients were enrolled with persistent asthma, taking steps 2, 3 or 4 of British Thoracic Society guidelines, with an ICS dose up to 2000ug/day (Clenil equivalent dose) of large particle ICS with or without long acting β2 adrenoceptor agonist (LABA), long acting muscarinic antagonists (LAMA) or leukotriene receptor antagonist (LTRA). Patients were requested to stop any second line controller therapy and were then converted to a reference large particle ICS as Clenil pMDI for the subsequent step down and run-in phase. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Oct 2013
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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: 74
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Worldwide total number of subjects |
74
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EEA total number of subjects |
74
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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) |
66
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
Subject recruitment began 28 October 2013 and the study completed on 25 June 2018. Of the 74 patients screened, 26 were randomised and 24 completed per protocol and were included in the final analysis. | |||||||||
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Pre-assignment
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Screening details |
Males and females with persistent asthma, aged 18-70 years, on inhaled corticosteroid (ICS) dose up to 2000 mcg/day (Clenil equivalent dose) of large particle ICS with or without long acting β2 agonist (LABA), long acting muscarinic antagonists (LAMA) or leukotriene receptor antagonist (LTRA), FEV1 at least 60% predicted, ACQ at least 1.0. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
74 | |||||||||
Number of subjects completed |
26 | |||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Did Not Meet Inclusion Criteria: 44 | |||||||||
Reason: Number of subjects |
Adverse event, non-fatal: 2 | |||||||||
Reason: Number of subjects |
Elective Procedure Scheduled: 1 | |||||||||
Reason: Number of subjects |
Family Bereavement: 1 | |||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Qvar (Baseline) | |||||||||
Arm description |
- | |||||||||
Arm type |
Baseline Measurements | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Qvar (8 weeks) | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Qvar
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pressurised inhalation
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Routes of administration |
Inhalation use
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Dosage and administration details |
Following their run-in phase, each subject was switched to an equivalent daily dose of Qvar, which was continued unchanged over an 8-week period.
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Baseline characteristics reporting groups [1]
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: The worldwide number enrolled is the number of subjects screened into the study (74). The number of subjects in the baseline period is the number who were then randomised into the study (26). Of these 26 subjects, 24 completed the study per protocol and were able to be analysed. |
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End points reporting groups
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Reporting group title |
Qvar (Baseline)
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Reporting group description |
- | ||
Reporting group title |
Qvar (8 weeks)
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Reporting group description |
- | ||
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End point title |
ACQ | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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Statistical analysis title |
Repeated Measures ANOVA | ||||||||||||
Statistical analysis description |
The null hypothesis proposed is that compared to the post run-in baseline on coarse-particle ICS; there would
be no difference in asthma control (as ACQ) after switching to extra-fine ICS treatment at the equivalent
dose. The study was designed with at least 80% power to detect a 0.4 unit change in the primary outcome of ACQ at 8 weeks, assuming a standard deviation of 0.68, with an alpha error (two tailed) of 0.05, requiring at least 23 patients to complete per protocol.
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Comparison groups |
Qvar (Baseline) v Qvar (8 weeks)
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Number of subjects included in analysis |
48
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Analysis specification |
Post-hoc
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Analysis type |
equivalence | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANOVA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.53
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.83 | ||||||||||||
upper limit |
-0.23 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.12
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End point title |
mAQLQ | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
FEV1 (%) predicted | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
FEF25-75 (%) predicted | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
AX (kPa/L) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
R5 (kPa/L.s) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
R5-R20 (kPa/L.s) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
FeNO (ppb) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Eosinophils | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
PEF AM | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
PEF PM | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Symptoms AM | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Symptoms PM | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Reliever AM | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Reliever PM | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mannitol PD15 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mannitol RDR | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparisons were made at baseline after patients were on a constant dose of fine-particle ICS and after 8 weeks of switching to an equivalent dose of extra-fine particle hydrofluoroalkane beclometasone dipropionate (Qvar).
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All adverse events (AEs) were recorded from the time a participant consented to join the study until the last study visit.
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Adverse event reporting additional description |
Participants were asked about the occurrence of AEs at each study visit and received training on how to record AEs and concomitant medications. All AEs were recorded on subject-specific logs.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
Completed Per Protocol
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Aug 2014 |
REC & MHRA Amendment - Amendment to enable inclusion of patients already receiving extra-fine particle inhaled corticosteroids. |
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15 Apr 2016 |
REC Amendment - Amendment to seek prospective approval of patient-facing documents. |
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02 Jun 2017 |
REC Amendment - Clarifications of inclusion criteria, notification of new equipment used in study, notification of department name change, changes to study paperwork in line with new guidelines. |
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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 | |||
