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

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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.


  • Jan Stolk
  • Robert A. Stockley
  • Berend C. Stoel
  • Brendan G. Cooper
  • Eeva Piitulainen
  • Niels Seersholm
  • Kenneth R. Chapman
  • Jonathan G. W. Burdon
  • Marc Decramer
  • Raja T. Abboud
  • Gregorius P. M. Mannes
  • Emiel F. Wouters
  • Jeffrey E. Garrett
  • Juan C. Barros-Tizon
  • Erich W. Russi
  • David A. Lomas
  • William A. MacNee
  • Alexis Rames
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Respiratory Medicine and Allergy


  • alpha(1)-antitrypsin, chronic obstructive pulmonary disease treatment, clinical trials, densitometry, emphysema, retinoids
Original languageEnglish
Pages (from-to)306-312
JournalEuropean Respiratory Journal
Issue number2
Publication statusPublished - 2012
Publication categoryResearch