Prednisolone or Dexamethasone in Acute Adult Asthma

Clinical Question: Is a single dose of dexamethasone not inferior to 5 days of prednisolone to treat mild to moderate asthma exacerbation in adults?

Title of the Paper: A Randomized Controlled Noninferiority Trial of Single Dose of Oral Dexamethasone Versus 5 Days of Oral Prednisolone in Acute Adult Asthma

Authors: Rehrer, M.W. et al

Published: Annals of Emergency Medicine, Nov 2016

Population: Adults 18-55yrs requiring nebulisers in ED but able to be discharged home (with exclusions)

Intervention: 12mg dexamethasone in ED and 4 additional placebo capsules

Comparator: 60mg prednisolone OD for 5 days

Outcome: Relapse within 14 days

Summary: This is a single centre study. The authors hypothesised that because there is an association between poor adherence and poor outcomes in asthma, a dose of dexamethasone, known to have a duration of action of 72 hours, could improve outcomes compared to normal standard of care, which requires 5 days of adherence.

The ED staff, patients, and analysers were all blinded to treatment allocation. Anyone who received a nebuliser was screened for possible eligibility. Relapse was detected by telephone follow-up at 2 weeks.

The authors chose a noninferiority margin on 8%. This is because national records and previous studies find a 16% relapse rate for normal standard of care, and a 33% relapse rate for placebo. They state that 50% of the difference between these two relapse rates is 8%. Choosing 8% as a non-inferiority margin also ensures the intervention is >50% superior to placebo.

This study included 376 adults, 173 in dexamethasone group and 203 in prednisolone controls. Relapse occurred for 12.1% taking dexamethasone, and 9.8% taking prednisolone. 95% confidence interval -4.1% to 8.6%. They state that because this is very slightly greater than their pre-planned noninferiority margin of 8%, a single dose of dexamethasone does not demonstrate noninferiority to prednisolone for 5 days.


Strengths, weaknesses, and clinical relevance

I think the paper is very clearly written and methods thoroughly described.

This study relies on noninferiority methodology. They are testing that the new intervention is ‘not unacceptably worse’ than current care, by an arbitrarily chosen margin. By falling outside of their planned margin, the authors can only say that statistically dexamethasone is “not ‘not unacceptably worse'” than prednisolone.

The authors do not describe their local population. It could be presumed that in a context where patients are  less likely to engage with counting out 8 x 5mg prednisolone tablets for 5 days, there would be higher rate of relapse in the control group.

The confidence interval crosses 0 so ignoring the non-inferiority margin it could be considered that there is statistically no difference between the two groups.

The sample size was recalculated when the interim analysis found an overall relapse rate of 11%. The authors do not offer a breakdown of this between the two groups. They did not go on to redefine their noninferiority margin based on a greater difference between this relapse rate and historical placebo relapse rate, because this would have meant changing their outcomes mid-trial; however, should they have done so the noninferiority margin would have been ((33-11)/2=) 11% which would have meant their overall result of 8.6% would have demonstrated noninferiority.

Could the results be different in a UK context prescribing 30-40mg prednisolone instead of 60mg OD?

Is this relevant for the COPD population as well?

Could or should this study change practice here?

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2 thoughts on “Prednisolone or Dexamethasone in Acute Adult Asthma

  1. Thanks for an interesting paper. Some thoughts I have on this one.
    Well designed trial at outset with relevant clinical outcome. However –
    Significant loss to follow up of 20%
    I’m not an stats expert but changing the sample size calculation mid-trial doesn’t seem to be correct although I’m sure that recruitment was tricky.
    Interesting that the baseline overall relapse rate for the hospital was 16% but during the trial period was only 11%. Were other aspects of asthma management different during the study period?

    The results did breach their own defined threshold of 8% by a tiny amount.
    The population is different to our local ED population – most of the study group are black/latino, most not on inhaled steroids and 10-12% intubated in the past.
    Steroid dosage is different to UK.

    Overall not sure we can change our practice yet. Needs to be further work

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  2. Interesting – I haven’t read a ‘non-inferiority’ paper before (the link was helpful Nicola).

    It certainly doesn’t encourage you to change practice in the normal setting – but I wonder with someone who admits to poor compliance whether this would be a more appropriate treatment? I have never given more than 8mg stat mind.

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