This study evaluated the effects of atorvastatin for treating asthma patients through a double-blind randomized clinical trial. 62 patients with mild to moderate persistent asthma were alternately allocated to receive either atorvastatin or a placebo for 8 weeks. Asthma control was assessed before and after treatment using the Asthma Control Test questionnaire. The study found no significant differences in asthma control between the atorvastatin and placebo groups, indicating that atorvastatin was not effective for treating mild to moderate asthma over the study period based on the measures used. The summary discusses some limitations of the study related to sensitivity of outcome measures and potential bias from the alternating allocation method used.

1. Dr. Priyamadhaba Behera
Junior Resident
ARTICLE PRESENTATION ON
CLINICAL TRIAL
12/04/2013
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2. Evaluation of Atorvastatin for the Treatment of
Patients With Asthma: A Double-Blind Randomized
Clinical Trial
Abdollatif Moini, Ghasem Azimi, Abdolhay Farivar
Impact Factor 1.913

3. Outline of presentation
1.Summary of article (1-18)
–introduction
– objectives
– Methodology
– Results
– Discussion
2.Epidemiology and biostatics concepts related to
article (19-22)
3.Critical appraisal (23-30)

4. Introduction
• Asthma is a global health problem. Despite the
availability of effective treatment, some
patients develop a type of asthma that is
insensitive to corticosteroid
• The anti-inflammatory and immunomodulatory
effects of satins are well-documented

5. Objective
• the potential therapeutic effects of
atorvastatin were investigated in asthmatic
patients

6. METHODLOGY
Study Setting Hospital -based
Study site asthma clinics of Arak University of
Medical Sciences , Rahahan, Arak,
Iran
Type of Study Randomised clinical trial
Sample Size 62
Study Subjects 18-70 years(grade2/grade3)
asthmatic patients
Scales used Asthma Control Test Questionnaire
(For primary out-come) 6

7. Geographical location of study site

8. • Inclusion criteria –mild persistent/moderate
persistent asthmatic (grade 2/grade 3) aged in
between 18 to 70 years
• Exclusion criteria
1. taking satins at the time of study
2. h/o of sensitive to satins
3. severe asthma leading to hospitalization within a month
prior to study
4. Smoking
5. hepatitis or active liver disease, myopathy or myositis,
6. pregnancy

9. Methodology
mild persistent to moderate persistent asthma (grades 2 and 3 of severity criteria
for asthma) aged 18 to 70 years who presented at asthma clinics of Arak
University of Medical Sciences from 24 October 2010 to 10 April 2011
73 agreed to participate
Volunteer patients were alternately allocated to the intervention
and control group based on timing of entering study

10. Control group=6,intervention group=5

11. ASTHMA CONTROL TEST
• The ACT is a 5-item patient-administered survey for
assessing asthma control
• Each of the 5 questions is given a score from 1 to 5.
• Responses from the ACT are summed to yield a score
that ranges from 5 (poor control) to 25 (complete
control).
• A cut-off score of 19 or less identifies patients with
poorly controlled asthma.

12. Ethical clearance
• The research protocol was approved by the
Scientific Ethics Committee of Arak University
of Medical Sciences, and written informed
consent was obtained from the volunteers

13. STATISTICAL ANALYSIS
• Statistical analysis carried out with software SPSS 16.0
• Chi-squared test and student t-test were used to compare
the treatment and control group
• independent and dependent t-test were used for the
comparison of groups and subgroups
13

14. RESULT-1

15. RESULT-1 cont.
• Table 1.Demographic information continued

16. Result-2

17. DISCUSSION
 One probable reason for the lack of a significant clinical
response to satins in this study, as well as in other
human studies, is that the therapeutic effects observed
in vitro and in mice do not necessarily occur in humans
 Favourable clinical response requires a higher drug
dosage or a longer period of treatment, or that the
variables selected in this study were insufficiently
sensitive to show improved asthma control
 atorvastatin is not effective for the treatment of mild to
moderate asthma 17

18. Limitations
• Did not have access to more sensitive
quantitative methods for evaluating airway
hyper-responsiveness and inflammation.
eg: using a peak flow meter, methacholine
challenge test, CRP assay, number of saliva
eosinophils, the fraction of exhaled nitric oxide,
or alveolar nitric oxide.
18

19. Randomization
Randomization gives each participant a known (usually equal)
chance of being assigned to any of the groups. Successful
randomization requires that group assignment cannot be
predicted in advance.
Basic Benefits of Randomization
• Eliminates assignment basis
• Tends to produce comparable groups
• Produces valid statistical tests (valid false positive error
rates)

20. Why Randomize?
• If, at the end of a clinical trial, a difference in outcomes
occurs between two treatment groups (say, intervention
and control) possible explanations for this difference
would include:
• the intervention exhibits a real effect;
• the outcome difference is solely due to chance
• there is a systematic difference (or bias) between the
groups due to factors other than the intervention.
Randomization aims to obviate the third possibility.

21. Forms of Randomization
• Simple Randomization
• Permuted Block Randomization
• Stratified Block Randomization
• Dynamic (adaptive) random allocation

22. Alternative allocation vs.
Randomisation
• Some investigators incorrectly believe that an
alternating assignment of participants to the
intervention and the control groups (eg-ABABAB…..)
is a randomization
• No random components exits in this type of
allocation except the first participant
• A single-blind or unblinded study, the investigators
know the next assignment that lead to bias
• In double-blind study, if the the blind is broken at
one participant then entire sequence of assignment
is known

23. CRITICAL APPRAISAL
CONSORT (CONsolidated Standards of Reporting
Trials)

24. CRITICAL APPRAISAL-1
• Title and abstract are clear with study design,
balanced summary of what was found
• Background explains the scientific rationale for the
study
• In objectives they mention that the study, the
potential therapeutic effects of atorvastatin were
investigated in asthmatic patients ,but they have
only considered grade-2/3 asthmatic patients in the
study
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25. CRITICAL APPRAISAL-2
• Inclusion and exclusion criteria for participants are clear
• Settings and locations where the data were collected are
mentioned
• The interventions for each group with sufficient details to
allow replication, including how and when they were actually
administered
• Completely defined pre-specified primary and secondary
outcome measures, including how and when they were
assessed
How sample size was determined is explained

26. CRITICAL APPRAISAL-3
• Detail description of randomisation is not given
• Alternately allocation doesn't survey the purpose of
randomisation
• Statistical methods used to compare groups for
primary and secondary outcomes are mentioned
• A table showing baseline demographic and clinical
characteristics for each group
• Participant flow diagram is given but steps of
randomisation and voluntary data missing is not
clear

27. CRITICAL APPRAISAL-4
• Silent about possible bias
• Internal validity is questionable d/o selection
bais
• Generalisability of this result is not possible to
all asthmatic patient as it uses grade-2/3
asthma in sampling
• Silent about funding
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THANK YOU
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