Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments

Ther Adv Respir Dis. 2010 Dec;4(6):319-32. doi: 10.1177/1753465810379617. Epub 2010 Oct 6.

Abstract

Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene©, an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population. This article describes the study design as well as the effectiveness of the quality control that was implemented on the key efficacy endpoints, based on data derived from the placebo-treated subjects. In this multicentre, multinational study the implementation of standardized procedures included: careful site selection, use of trained staff, regular monitoring and machine calibration, use of biological controls and regular feedback to sites by an independent quality control centre. All of these procedures resulted in high-quality measurements of lung density, spirometry, static lung volumes and gas transfer. It was also confirmed that CT lung density was the most sensitive endpoint followed by TLco, FEV(1) and RV measured by body box.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Double-Blind Method
  • Emphysema
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Emphysema / drug therapy*
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / physiopathology
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Quality Control
  • Receptors, Retinoic Acid / agonists*
  • Research Design
  • Respiratory Function Tests
  • Retinoic Acid Receptor gamma
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • alpha 1-Antitrypsin Deficiency / complications*

Substances

  • Pyrazoles
  • Receptors, Retinoic Acid
  • Stilbenes
  • Palovarotene