Clinical Trial Results:
What is the clinical and cost effectiveness of oral steroids in the treatment of acute lower respiratory tract infection (LRTI)? A placebo controlled randomised trial
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Summary
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EudraCT number |
2012-000851-15 |
Trial protocol |
GB |
Global end of trial date |
27 Feb 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
10 May 2018
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First version publication date |
10 May 2018
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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 |
UoB1581
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Additional study identifiers
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ISRCTN number |
ISRCTN57309858 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
NHS REC: 12/SW/0180, EudraCT: 2012-000851-15, NIHR CSP: 102138 | ||
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Sponsors
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Sponsor organisation name |
University of Bristol
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Sponsor organisation address |
Senate House, Tyndall Avenue, Bristol, United Kingdom, BS8 1TH
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Public contact |
Birgit Whitman, University of Bristol, +44 01173317130, birgit.whitman@bristol.ac.uk
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Scientific contact |
Birgit Whitman, University of Bristol, +44 01173317130, birgit.whitman@bristol.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 |
18 Jul 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Jan 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Feb 2015
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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 use of oral prednisolone reduce the duration of moderately bad or worse cough and / or the severity of all its associated symptoms on days 2 to 4 by at least 20% when compared to no steroid treatment in adults ≥18 years presenting to primary care with acute LRTI?
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Protection of trial subjects |
All Serious Adverse events were reported to the UH Bristol contact and Centre Principal Investigator by a delegated member of the research team within 24 hours of their knowledge of the event.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 398
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Worldwide total number of subjects |
398
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EEA total number of subjects |
398
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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) |
336
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From 65 to 84 years |
62
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted between July 2013 and October 2014. Family physicians and nurses (recruiting clinicians) were trained in study procedures by 4 centres at the Universities of Bristol, Southampton, Nottingham, and Oxford. Fifty-eight family physicians and 50 practice nurses based in 54 family practices assessed patients for suitability. | |||||||||
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Pre-assignment
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Screening details |
525 patients were assessed for suitability, of whom; 124 were excluded due to ineligibility, 4 declined participation and 401 were randomised. | |||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||
Blinding implementation details |
The treatment allocation schedule was computer generated by a statistician independent of the trial team in a 1:1 ratio, using a variable block size (4, 6, 8 and 10). Allocated medication was added to numbered participant packs by pharmacists independent of the team. All packs were identical, containing either 20mg oral prednisolone tablets (Galen Pharma GmbH) or placebo tablets matched on dimension, appearance and taste (Piramal Healthcare Ltd).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Prednisolone | |||||||||
Arm description |
Participant packs containing ten 20-mg oral prednisolone tablets (Galen Pharma GmbH). Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription).
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Arm title
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Placebo | |||||||||
Arm description |
Participant packs containing ten 20-mg placebo tablets matched on dimension, appearance and taste (Piramal Healthcare Ltd) to oral prednisolone tablets. Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo (no active ingredient)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before stating any antibiotics (if receiving a "delayed" prescription).
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Baseline characteristics reporting groups
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Reporting group title |
Prednisolone
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Reporting group description |
Participant packs containing ten 20-mg oral prednisolone tablets (Galen Pharma GmbH). Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participant packs containing ten 20-mg placebo tablets matched on dimension, appearance and taste (Piramal Healthcare Ltd) to oral prednisolone tablets. Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Prednisolone
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Reporting group description |
Participant packs containing ten 20-mg oral prednisolone tablets (Galen Pharma GmbH). Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | ||
Reporting group title |
Placebo
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Reporting group description |
Participant packs containing ten 20-mg placebo tablets matched on dimension, appearance and taste (Piramal Healthcare Ltd) to oral prednisolone tablets. Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | ||
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End point title |
PO: Duration of moderately bad or worse cough (0-28 days) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline up to 28 days. If the patient was still suffering from a cough by day 28 then they were censored at this time point.
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Statistical analysis title |
Duration of MBW cough (censored at 28) | ||||||||||||
Statistical analysis description |
Adjusted for centre and prior duration of cough
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Comparison groups |
Prednisolone v Placebo
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Number of subjects included in analysis |
334
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.89 | ||||||||||||
upper limit |
1.39 | ||||||||||||
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End point title |
PO: Severity of symptoms | ||||||||||||
End point description |
Mean severity score of the 6 main symptoms (cough, phlegm, shortness of breath, sleep disturbance, feeling generally unwell and activity disturbance) on days 2-4; the mean score was calculated across the symptoms for each day and then the overall mean was calculated with a maximum value of 6.
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End point type |
Primary
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End point timeframe |
On days 2-4
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Statistical analysis title |
Difference in mean symptom severity score | ||||||||||||
Statistical analysis description |
Adjusted for centre and baseline severity
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Comparison groups |
Placebo v Prednisolone
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Number of subjects included in analysis |
369
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.05 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.4 | ||||||||||||
upper limit |
0 | ||||||||||||
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End point title |
Mean area under the curve for cough symptoms | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their cough on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
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End point type |
Secondary
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End point timeframe |
0-28 days
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Statistical analysis title |
Cough symptoms - area under the curve | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline prior duration of cough
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Comparison groups |
Placebo v Prednisolone
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Number of subjects included in analysis |
364
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.43
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-7.66 | ||||||||||||
upper limit |
2.8 | ||||||||||||
| Notes [1] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
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End point title |
Mean area under the curve for phlegm symptoms | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their phlegm on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
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End point type |
Secondary
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End point timeframe |
Day 1-28
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Statistical analysis title |
Difference in mean area under the curve for phlegm | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
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Comparison groups |
Prednisolone v Placebo
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
superiority [2] | ||||||||||||
P-value |
= 0.09 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-4.1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-8.89 | ||||||||||||
upper limit |
0.7 | ||||||||||||
| Notes [2] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
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End point title |
Mean area under the curve for shortness of breath | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Patients were asked each day to measure the severity score of their shortness of breath on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
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Statistical analysis title |
Difference in mean area under the curve for shrtb | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
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Comparison groups |
Prednisolone v Placebo
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
= 0.27 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-6.34 | ||||||||||||
upper limit |
1.75 | ||||||||||||
| Notes [3] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
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End point title |
Mean area under the curve for wheeze | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their wheeze on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
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End point type |
Secondary
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End point timeframe |
0-28 days
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Statistical analysis title |
Difference in mean area under the curve for wheeze | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
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Comparison groups |
Prednisolone v Placebo
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Number of subjects included in analysis |
362
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Analysis specification |
Pre-specified
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Analysis type |
superiority [4] | ||||||||||||
P-value |
= 0.92 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.18
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.27 | ||||||||||||
upper limit |
3.64 | ||||||||||||
| Notes [4] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
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End point title |
Mean area under the curve for blocked or runny nose | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their blocked/runny nose on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
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End point type |
Secondary
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End point timeframe |
0-28 days
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Statistical analysis title |
Difference in mean area under the curve for nose | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
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Comparison groups |
Prednisolone v Placebo
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Number of subjects included in analysis |
361
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Analysis specification |
Pre-specified
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Analysis type |
superiority [5] | ||||||||||||
P-value |
= 0.76 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.67
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.7 | ||||||||||||
upper limit |
5.05 | ||||||||||||
| Notes [5] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for chest pain | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their chest pain on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for chestp | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
361
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [6] | ||||||||||||
P-value |
= 0.05 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.92
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.83 | ||||||||||||
upper limit |
-0.01 | ||||||||||||
| Notes [6] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for fever | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their fever on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for fever | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
361
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [7] | ||||||||||||
P-value |
= 0.68 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.33
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.9 | ||||||||||||
upper limit |
1.24 | ||||||||||||
| Notes [7] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for muscle ache | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their muscle ache on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for muscle | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
361
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [8] | ||||||||||||
P-value |
= 0.35 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.61
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.99 | ||||||||||||
upper limit |
1.77 | ||||||||||||
| Notes [8] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for headache | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their headache on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for headac | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
361
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [9] | ||||||||||||
P-value |
= 0.74 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.62
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.34 | ||||||||||||
upper limit |
3.09 | ||||||||||||
| Notes [9] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for sleep disturbance | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their sleep disturbance on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for sleep | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
362
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [10] | ||||||||||||
P-value |
= 0.76 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.75
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.6 | ||||||||||||
upper limit |
4.1 | ||||||||||||
| Notes [10] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for feeling generally unwell | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of how well they felt in generally on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for unwell | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
361
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [11] | ||||||||||||
P-value |
= 0.12 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.25
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-7.38 | ||||||||||||
upper limit |
0.89 | ||||||||||||
| Notes [11] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis. |
|||||||||||||
|
|||||||||||||
End point title |
Mean area under the curve for activity disturbance | ||||||||||||
End point description |
Patients were asked each day to measure the severity score of their activity disturbance on a scale of 0 (not affected) - 6 (as bad as it could be). The area under the curve was then calculated for each patient for the total 28 days.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
0-28 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in mean area under the curve for active | ||||||||||||
Statistical analysis description |
Area under the curve adjusted for centre and baseline presence/absence of symptom (previous 24 hours)
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
361
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [12] | ||||||||||||
P-value |
= 0.02 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-4.78
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-8.86 | ||||||||||||
upper limit |
-0.69 | ||||||||||||
| Notes [12] - Although the statistical technique (area under the curve) was not pre-specified the team did say that they would explore the duration and severity of other symptoms in a secondary analysis |
|||||||||||||
|
|||||||||||||
End point title |
Duration of moderately bad or worse cough (0-56 days) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline up to 56 days. If the patient was still suffering from a cough by day 56 then they were censored at this time point.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Duration of MBW cough (censored at 56) | ||||||||||||
Statistical analysis description |
Adjusted for centre and prior duration of cough
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
334
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.89 | ||||||||||||
upper limit |
1.39 | ||||||||||||
|
|||||||||||||
End point title |
Duration of cough (0-56 days) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline up to 28 days. If the patients was still suffering from a cough by day 56 then they were censored at this time point.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Duration of cough (censored at 56) | ||||||||||||
Statistical analysis description |
Adjusted for centre and prior duration of cough
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
373
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.29 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.9 | ||||||||||||
upper limit |
1.42 | ||||||||||||
|
|||||||||||||
End point title |
Duration of abnormal peak flow (0-28 days) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline up to 28 days. Counted as the number of days the patient had a peak flow rate that was <80% of their expected level.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Duration of abnormal peak flow (censored at 28d) | ||||||||||||
Statistical analysis description |
Adjusted for centre and prior duration of cough
|
||||||||||||
Comparison groups |
Prednisolone v Placebo
|
||||||||||||
Number of subjects included in analysis |
232
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.58 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.79 | ||||||||||||
upper limit |
1.52 | ||||||||||||
|
||||||||||||||||
End point title |
Antibiotic use (up to 7 days) | |||||||||||||||
End point description |
||||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From baseline up to 7 days. Patients were counted if they reported consuming antibiotics on any of the 7 days.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Odds ratio for the antibiotic consumption (0-7) | |||||||||||||||
Statistical analysis description |
Adjusted for centre and whether the patient was given a delayed antibiotic script at baseline
|
|||||||||||||||
Comparison groups |
Prednisolone v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
373
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.96 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
0.98
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.42 | |||||||||||||||
upper limit |
2.28 | |||||||||||||||
|
||||||||||||||||
End point title |
Antibiotic use (up to 28 days) | |||||||||||||||
End point description |
||||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From baseline up to 28 days. Patients were counted if they reported consuming antibiotics on any of the 28 days.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Odds ratio for the antibiotic consumption (0-28) | |||||||||||||||
Statistical analysis description |
Adjusted for centre and whether the patients was given a delayed antibiotic script at baseline
|
|||||||||||||||
Comparison groups |
Prednisolone v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
373
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.39 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
0.78
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.44 | |||||||||||||||
upper limit |
1.39 | |||||||||||||||
|
||||||||||||||||
End point title |
Patient satisfaction (feel better) | |||||||||||||||
End point description |
On day 28, patients were asked if they agreed or disagreed with "my OSAC trial tablets helped me to feel better from my cough". The proportions of participants responding 'agree' (as opposed to 'neither agree or disagree' and 'disagree') were compared between the groups.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
None. Asked at the end of the symptom diary (day 28).
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Odds ratio for patient satisfaction (feel better) | |||||||||||||||
Statistical analysis description |
Adjusted for centre
|
|||||||||||||||
Comparison groups |
Prednisolone v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
349
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.11 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
1.46
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.92 | |||||||||||||||
upper limit |
2.34 | |||||||||||||||
|
||||||||||||||||
End point title |
Patient satisfaction (future use) | |||||||||||||||
End point description |
On day 28, patients were asked if they agreed or disagreed with "my OSAC trial tablets helped me to feel better from my cough". The proportions of participants responding 'agree' (as opposed to 'neither agree or disagree' and 'disagree') were compared between the groups.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
None. Asked at the end of the symptom diary (day 28).
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Odds ratio for patient satisfaction (future use) | |||||||||||||||
Statistical analysis description |
Adjusted for centre
|
|||||||||||||||
Comparison groups |
Prednisolone v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
349
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.16 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
1.36
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.89 | |||||||||||||||
upper limit |
2.08 | |||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Serious adverse events were collected throughout the 28 day follow up period. Non-serious adverse events were collected for the first 7 days only (treatment course=5 days).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events were then categorised as expected, unexpected or related to cough.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
SPC and/or BNF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
Latest
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prednisolone
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participant packs containing ten 20-mg oral prednisolone tablets (Galen Pharma GmbH). Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participant packs containing ten 20-mg placebo tablets matched on dimension, appearance and taste (Piramal Healthcare Ltd) to oral prednisolone tablets. Participants were asked to take 2 tablets once daily for 5 days, starting on the day of consultation, if possible before starting any antibiotics (if receiving a "delayed" prescription). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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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/28829884 |
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