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

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

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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.
Original languageEnglish
Pages (from-to)306-312
JournalEuropean Respiratory Journal
Issue number2
Publication statusPublished - 2012

Subject classification (UKÄ)

  • Respiratory Medicine and Allergy

Free keywords

  • alpha(1)-antitrypsin
  • chronic obstructive pulmonary disease treatment
  • clinical trials
  • densitometry
  • emphysema
  • retinoids


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