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Original research
Single dose of budesonide/formoterol turbuhaler compared to salbutamol pMDI for speed of bronchodilator onset in asthma: a randomised cross-over trial
  1. Nethmi Kearns1,
  2. Mathew Williams1,
  3. Pepa Bruce1,
  4. Melissa Black1,
  5. Ciléin Kearns1,
  6. Jenny Sparks1,
  7. Irene Braithwaite1,2,
  8. Mark Weatherall1,3,
  9. Richard Beasley1,2
  1. 1Medical Research Institute of New Zealand, Wellington, New Zealand
  2. 2School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand
  3. 3Medicine, University of Otago Wellington, Wellington, New Zealand
  1. Correspondence to Dr Nethmi Kearns, Medical Research Institute of New Zealand, Wellington, New Zealand; nethmi.kearns{at}mrinz.ac.nz

Abstract

Objective To compare bronchodilator response after to salbutamol and budesonide/formoterol in adults with stable asthma.

Methods A double-blind, cross-over, single-centre, placebo-controlled, non-inferiority trial. Adults with stable asthma were randomised to different orders of two treatment regimens: two actuations of placebo via MDI and one actuation of budesonide/formoterol 200/6 µg via turbuhaler; and one actuation of placebo turbuhaler and two actuations of salbutamol 100 µg via MDI. The primary outcome measure was FEV1 after 2 min. Secondary outcome measures included FEV1, mBorg Dyspnoea Scale score and visual analogue score for breathlessness over 30 min.

Results Forty-nine of 50 potential participants were randomised. One participant withdrew following the first intervention visit and another could not be randomised due to COVID-19 restrictions. The mean (SD) change from baseline FEV1 2 min after treatment administration for budesonide/formoterol and salbutamol was 0.08 (0.14) L, n=49, and 0.17 (0.18) L, n=48, respectively, mean (95% CI) paired difference of −0.097 L (−0.147 to −0.047), p=0.07, against a non-inferiority bound of −0.06 L. In the secondary analysis, FEV1 over 30 min was lower for budesonide/formoterol compared with salbutamol, difference (95% CI): −0.10 (−0.12 to −0.08) L, p<0.001. There were no differences in Visual Analogue Scale score or mBorg Dyspnoea Scale score between treatments.

Conclusion The results do not support the primary hypothesis of non-inferiority at the boundary of −0.06 L for the difference between budesonide/formoterol 200/6 µg compared with salbutamol 200 µg for FEV1 at 2 min, and could be consistent with inferiority with a p value of 0.07. For the secondary analysis of FEV1 measurements over time, the FEV1 was higher with salbutamol.

Trial registration number Australian and New Zealand Clinical Trials Registry (ACTRN 12619001387112).

  • inhaler devices
  • asthma

Data availability statement

Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices) will be available one year after publication until a minimum of 5 years after publication. It will be available to researchers who provide a methodologically sound proposal that has been approved by the study steering committee to achieve the aims outlined in the approved proposal. Data can be obtained through a signed data access agreement. The agreement can be obtained by emailing the Principal Investigator: richard.beasley@mrinz.ac.nz. The study protocol is available publicly on the ANZCTR website.

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Data availability statement

Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices) will be available one year after publication until a minimum of 5 years after publication. It will be available to researchers who provide a methodologically sound proposal that has been approved by the study steering committee to achieve the aims outlined in the approved proposal. Data can be obtained through a signed data access agreement. The agreement can be obtained by emailing the Principal Investigator: richard.beasley@mrinz.ac.nz. The study protocol is available publicly on the ANZCTR website.

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Footnotes

  • Contributors NK, MathewW, RB and IB were involved in the conception and design of the study. NK drafted the manuscript. NK, RB and MarkW contributed to the interpretation of data. NK, MathewW, PB, MB, CK and JS contributed to the acquisition of data. NK, MathewW, PB, MB, CK, JS, IB and RB were involved in the conduct of the study. MarkW was the study statistician. All authors contributed to the revision of the manuscript. NK and RB are guarantors for the manuscript.

  • Funding This trial was supported by Health Research Council of New Zealand Independent Research Organisation grant IRO [18/002].

  • Competing interests RB has received research funding from Genentech, AstraZeneca and Health Research Council New Zealand and CureKids (NZ) and personal fees from AstraZeneca, Cipla, Avillion and Theravance all outside the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.