Randomised controlled trial for emphysema with a selective agonist of the γ-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

75 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftEuropean Respiratory Journal
Vol/bind40
Udgave nummer2
Sider (fra-til)306-12
Antal sider7
ISSN0903-1936
DOI
StatusUdgivet - aug. 2012

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