Transcript Budesonide/formoterol as effective as prednisolone plus

Budesonide/formoterol as
effective as prednisolone plus
formoterol
in acute exacerbations of COPD
A double-blind, randomised,
non-inferiority, parallel-group,
multicentre study
Done by:
Khalid Al-Rashdi
R3
Non-inferiority is a kind of similarity within a limit. The limit
is the degree of tolerable inferiority of the new drug
compared with the standard treatment .
if the non-inferiority limit is set at 7·5%, an increase in the incidence of
serious events or deaths—say 7% instead of the 5% currently
established for the comparator—is not seen as large enough to
mark a difference between the new and the control drug. The new
drug will therefore be considered non-inferior to the old drug.
Introduction:
-
Chronic obstructive pulmonary disease (COPD) is a
major health problem and cause of death and disability.
- up to 90% of all COPD patients with exacerbations can be
treated at primary health care centres and thereafter
return home with intensified therapy.
- oral corticosteroids represent standard treatment for
COPD exacerbations.
-
2-week course of inhale budesonide/formoterol would be
equally effective for treatment of acute COPD
exacerbations as standard therapy in patients judged by
the investigator not to require hospitalisation.
- the initial 2-week treatment would influence the rate of
exacerbations during a subsequent 12-week open-label
treatment period with the fixed combination of
budesonide and formoterol at a standard dose of 320/9
μg bid.
-
-Department of Public Health and Caring Sciences,

Family Medicine and Clinical Epidemiology, Uppsala
University, Sweden.
-done in one hospital and 29 health centers. 
Published: 19 February 2009
Respiratory Research 2009, 10:11 doi:10.1186/1465-992110-11
This article is available from: http://respiratoryresearch.com/content/10/1/11
Methods:
-double-blind, randomised, non-inferiority, parallel-group,
multicentre study comparing two treatment strategies.
-two weeks' treatment with inhaled 
budesonide/formoterol (320/9 μg, qid) was compared
with prednisolone (30 mg once daily) plus inhaled
formoterol (9 μg bid) in patients with acute
exacerbations of COPD attending a primary health care
centres.

Inclusion criteria:
- ≥ 10 pack years,aged ≥ 40 years, with moderate COPD
corresponding to GOLD stage IIa or IIb ,COPD for ≥ 6
months prior to study entry.
-dyspnoea for less than one week
-FEV1 30–60% of predicted normal after acute
treatment with a single dose of oral corticosteroid plus
nebulised salbutamol/ipratropium bromide
-no requirement for subsequent immediate hospitalisation.
-subsequent open-label budesonide/formoterol (320/9 
μg bid) for another 12 week.
Exclusion criteria:
- diagnosis of asthma.
- a previous COPD exacerbation within 30 days prior to the
study.
- oxygen saturation < 92% after the initial acute
treatment.
- Requirement for oxygen therapy.
- a need for immediate hospitalisation as judged by the
investigator.
- treatment with any inhaled corticosteroid in doses > 1000
μg/day at study entry.
- use of or need for treatment with a non-selective βreceptor.
Assessments:
- end of weeks one and two, and at the end of the
open follow-up period. 

- The primary efficacy variable → change in FEV1 from
baseline to treatment.

- Other efficacy variables were treatment failures,FEV1 
measured twice daily at home with a Piko-1® electronic
peak flow meter, the number of patients with an
exacerbation and the time to first exacerbation during 
the follow-up period.
-A self administered Clinical COPD Questionnaire
(CCQ)was completed at the start of the study,
after one week and at the end of the double-blind period.
-At all visits serum C-reactive protein (CRP) concentrations.
-Safety was monitored by reporting of adverse events,
serious adverse events and discontinuations due to
adverse events.
Results:
-treatment failure:

2 cases in first group

-Use of reliever medication 
patients in the budesonide/formoterol and 
prednisolone plus formoterol groups used 1.8 and 2.1
inhalations per day of reliever medication, respectively.
Critical appraizal:

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Were the Pts in the two groups similar at
the start of the trial with respect to
prognostic factors?
Were Pts analysed in the groups to which
they were randomized
Blinding :

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Were Pts aware of group allocation?
Were clinicians aware of group allocation?
Were outcome assessors aware of group
allocation?
Were statisticians aware of group
allocation?

Were the follow up of Pts sufficiently long
& complete?
Absolute Risk Reduction (ARR):
The absolute arithmetic difference in events
rate .
ARR= EER – CER
after 1 week
=6.84 % -2.5% = 4.34%
after 2 week
=8.55 % -7.5% = 1.05%
Relative Risk Reduction (RRR):
Proportional reduction in rates of bad events
between experimental & control group in
trial .
RRR =(EER-CER)/CER
first week=(6.84 % -2.5 % ) /2.5% =173%
second =(8.55% -7.50)/7.50 =14%
Number Need to Treat ( NNT ):
The number of Pts who need to be treated
to achieve one additional favourable
outcome.
NNT = 1/ ARR
=1/4.34% = 23.04
=1/1.05%=95.24
Will the results help me in caring for my Pts?
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Were the study Pts similar to Pts in my
care?
Were all clinically important outcomes
considered?
Are the likely benefits worth the potential
harms & costs?
discussion:
- The risk of systemic side effects when using oral 
prednisolone – even short courses – has been well
recognised and the total steroid burden may be heavy in
patients with frequent exacerbations.
- Short-term increases in the doses of inhaled 
budesonide have been found safe and well tolerated
Limitation:
- lack of a placebo.
- this study included only patients who had a deterioration
of their clinical status during the last week prior to entry.
- all treatment effects were due to the initial single dose of
oral steroid plus the nebulisation of bronchodilators.
-duration of the prednisolone course (2 weeks)
-3-month follow-up period to be sufficient to evaluate
the incidence of further exacerbations.
-coast effective.
Conclusion:
- High dose budesonide/formoterol was as effective as
prednisolone plus formoterol for the ambulatory
treatment of acute exacerbations in non-hospitalized
COPD patients.
- An early increase in budesonide/formoterol dose may
therefore be tried before oral corticosteroids are used.
END 