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

Eur Respir J. 2012 Aug;40(2):306-12. doi: 10.1183/09031936.00161911. Epub 2012 Jan 26.


Palovarotene is an oral γ-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 α(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 α(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 end-point; 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 α(1)-antitrypsin deficiency.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Animals
  • Double-Blind Method
  • Emphysema / drug therapy*
  • Emphysema / metabolism
  • Female
  • Forced Expiratory Volume
  • Gases
  • Genotype
  • Humans
  • Inflammation
  • Least-Squares Analysis
  • Male
  • Middle Aged
  • Placebos
  • Pyrazoles / therapeutic use
  • Receptors, Retinoic Acid / agonists*
  • Smoking
  • Stilbenes / therapeutic use
  • Tomography, X-Ray Computed


  • Gases
  • Placebos
  • Pyrazoles
  • Receptors, Retinoic Acid
  • Stilbenes
  • retinoic acid receptor gamma
  • Palovarotene