Clinical Trial Results:
A Randomised Controlled Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis in patients with Pseudomonas Aeruginosa (Atorvastatin 1)
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Summary
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EudraCT number |
2010-022042-24 |
Trial protocol |
GB |
Global end of trial date |
31 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Aug 2020
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First version publication date |
01 Aug 2020
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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 |
Atorvastatin 1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01299194 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
ACCORD (University of Edinburgh & Lothian Healthboard)
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Sponsor organisation address |
47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ
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Public contact |
Dr Pallavi Bedi, University of Edinburgh, +44 01312426662, drpallavibedi@gmail.com
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Scientific contact |
Prof Adam Hill, NHS Lothian, +44 01312421921, adam.hill318@nhs.net
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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 |
10 Aug 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Dec 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
31 May 2017
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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 |
The aim of this randomised, double-blind controlled cross over study is to evaluate the efficacy of a 3 months treatment with atorvastatin versus placebo in patients with clinically significant bronchiectasis with colonisation with Pseudomonas aeruginosa.
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Protection of trial subjects |
The study was conducted in accordance with all relevant data protection, ethical and regulatory requirements to ensure the privacy and security of patient information and to ensure the rights, safety and well-being of the patients and the quality of the research data.
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Background therapy |
Excluded patients on a statin therapy. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Mar 2011
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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: 32
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Worldwide total number of subjects |
32
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EEA total number of subjects |
32
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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) |
13
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From 65 to 84 years |
19
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited from a meeting that they were invited to in the Royal Infirmary of Edinburgh, where information regarding the trial was provided. | |||||||||||||||
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Pre-assignment
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Screening details |
44 patients were screened for eligibility according to the protocol inclusion and exclusion criteria. 12 patients were excluded pre-randomisation: not meeting inclusion criteria (n = 9); declined to participate (n = 3); other reasons (n = 0). | |||||||||||||||
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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 | |||||||||||||||
Blinding implementation details |
Unmatched placebo
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Atorvastatin | |||||||||||||||
Arm description |
Atorvastatin | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Atorvastatin
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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 |
1 tablet daily at night
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Arm title
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Placebo | |||||||||||||||
Arm description |
Placebo | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet daily at night
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Atorvastatin
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Reporting group description |
Atorvastatin | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo | ||
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End point title |
Cough severity | |||||||||
End point description |
Cough severity measured by Leicester Cough Questionnaire (LCQ). LCQ scores from 3 till 21, where a lower score means worse quality of life.
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End point type |
Primary
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End point timeframe |
At the end of study - 3 months.
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Statistical analysis title |
Primary Outcome | |||||||||
Statistical analysis description |
We used a two-sided paired test with a 5% level of significance, 80% power, and a mean of difference of 1.3. The sample size was 26 subjects. To account for an approximate 20% dropout rate, we recruited 32 patients. We analyzed the study with a modified intention-to-treat model. We did not take the washout period into account. To compare the proportion of patients with either clinical improvement (measured by the LCQ) or quality of life gains (measured by the SGRQ), we used a McNemar test.
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Comparison groups |
Atorvastatin v Placebo
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Number of subjects included in analysis |
32
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
= 0.125 [2] | |||||||||
Method |
t-test, 2-sided | |||||||||
Confidence interval |
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| Notes [1] - We analyzed the study with a modified intention-to-treat model. For demographic and clinical variables, we presented data as mean (SD) for continuous variables and number (%) for categorical variables, unless otherwise stated. To examine continuous variables, we calculated the change during the atorvastatin period (either baseline-3 months or 4-7 months) and compared this to the change during the placebo period (either 4-7 months or baseline-3 months] by a paired t test. [2] - There was no evidence of a difference in the mean LCQ change in patients treated with atorvastatin compared with those treated with placebo (mean difference, 1.92; 95% CI, –0.57-4.41; P = .125). |
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Adverse events information
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Timeframe for reporting adverse events |
Within one week of the incident.
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Adverse event reporting additional description |
Adverse events were reported to the sponsor on the sponsors SAE reporting form.
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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 |
18.0
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Reporting groups
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Reporting group title |
Atorvastatin
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Mar 2011 |
Protocol v3 |
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21 Oct 2011 |
Protocol v4 |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29406231 |
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