Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptor

J. Stolk, R.A. Stockley, B C. Stoel, B.G. Cooper, E. Piitulainen, N. Seersholm, K.R. Chapman, J.G. Burdon, M. Decramer, R.T. Abboud, G.P. Mannes, E.F.M. Wouters, J.E. Garrett, J.C. Barros Tizon, E.W. Russi, D.A. Lomas, W.A. Macnee, A. Rames

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Palovarotene is an oral gamma-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement.

REPAIR (Retinoid treatment of Emphysema in Patients on the alpha(1)-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg.day(-1) palovarotene given for 1 year to 262 patients with severe alpha(1)-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary endpoint; functional end-points were also regularly assessed.

We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene.

Palovarotene 5 mg.day(-1) over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe alpha(1)-antitrypsin deficiency.

Original languageEnglish
Pages (from-to)306-312
Number of pages7
JournalEuropean Respiratory Journal
Volume40
Issue number2
DOIs
Publication statusPublished - Aug 2012

Keywords

  • alpha(1)-antitrypsin
  • chronic obstructive pulmonary disease treatment
  • clinical trials
  • densitometry
  • emphysema
  • retinoids
  • COMPUTED-TOMOGRAPHY DENSITOMETRY
  • OBSTRUCTIVE PULMONARY-DISEASE
  • AUGMENTATION THERAPY
  • CT DENSITOMETRY
  • LUNG-FUNCTION
  • PROGRESSION
  • EXACERBATIONS
  • ELASTASE

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