Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: A randomised controlled trial

Jane Davies, Helen Sheridan, Nicholas Bell, Steve Cunningham, Stephanie Davis, J. Stuart Elborn, Carlos E. Milla, Timothy D. Starner, Daniel J. Weiner, Po Shun Lee, Felix Ratjen

Research output: Contribution to journalArticle

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Abstract

Background: Ivacaftor has shown a clinical benefit in patients with cystic fibrosis who have the G551D-CFTR mutation and reduced lung function. Lung clearance index (LCI) using multiple-breath washout might be an alternative to and more sensitive method than forced expiratory volume in 1 s (FEV1) to assess treatment response in the growing number of children and young adults with cystic fibrosis who have normal spirometry. The aim of the study was to assess the treatment effects of ivacaftor on LCI in patients with cystic fibrosis, a G551D-CFTR mutation, and an FEV1 >90% predicted. Methods: This phase 2, multicentre, placebo-controlled, double-blind 2×2 crossover study of ivacaftor treatment was conducted in patients with cystic fibrosis, at least one G551D-CFTR allele, and an FEV1 >90% predicted. Patients also had to have an LCI higher than 7·4 at screening, age of 6 years or older, and a weight higher than or equal to 15 kg. Eligible patients were randomly allocated to receive one of two treatment sequences (placebo first followed by ivacaftor 150 mg twice daily [sequence 1] or ivacaftor 150 mg twice daily first followed by placebo [sequence 2]) of 28 days' treatment in each period, with a 28-day washout between the two treatment periods. Randomisation (ratio 1:1) was done with block sizes of 4, and all site personnel including the investigator, the study monitor, and the Vertex study team were masked to treatment assignment. The primary outcome measure was change from baseline in LCI. The study is registered at ClinicalTrials.gov, NCT01262352. Findings: Between February and November, 2011, 21 patients were enrolled, of which 11 were assigned to the sequence 1 group, and 10 to the sequence 2 group. 20 of these patients received treatment and 17 completed the trial (eight in sequence 1 group and 9 in sequence 2 group). Treatment with ivacaftor led to significant improvements compared with placebo in LCI (difference between groups in the average of mean changes from baseline at days 15 and 29 was -2·16 [95% CI -2·88 to -1·44]; p1 in detecting response to intervention in these patients with mild lung disease. Funding: Vertex Pharmaceuticals Incorporated.

Original languageEnglish (US)
Pages (from-to)630-638
Number of pages9
JournalThe Lancet Respiratory Medicine
Volume1
Issue number8
DOIs
StatePublished - Oct 2013
Externally publishedYes

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Spirometry
Cystic Fibrosis
Randomized Controlled Trials
Lung
Mutation
Forced Expiratory Volume
Placebos
Therapeutics
ivacaftor
Random Allocation
Cross-Over Studies
Lung Diseases
Young Adult
Alleles
Research Personnel
Outcome Assessment (Health Care)
Weights and Measures

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry : A randomised controlled trial. / Davies, Jane; Sheridan, Helen; Bell, Nicholas; Cunningham, Steve; Davis, Stephanie; Elborn, J. Stuart; Milla, Carlos E.; Starner, Timothy D.; Weiner, Daniel J.; Lee, Po Shun; Ratjen, Felix.

In: The Lancet Respiratory Medicine, Vol. 1, No. 8, 10.2013, p. 630-638.

Research output: Contribution to journalArticle

Davies, Jane ; Sheridan, Helen ; Bell, Nicholas ; Cunningham, Steve ; Davis, Stephanie ; Elborn, J. Stuart ; Milla, Carlos E. ; Starner, Timothy D. ; Weiner, Daniel J. ; Lee, Po Shun ; Ratjen, Felix. / Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry : A randomised controlled trial. In: The Lancet Respiratory Medicine. 2013 ; Vol. 1, No. 8. pp. 630-638.
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AU - Cunningham, Steve

AU - Davis, Stephanie

AU - Elborn, J. Stuart

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AU - Ratjen, Felix

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