Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study

Andrea M. D'Armini, Hossein Ardeschir Ghofrani, Nick H. Kim, Eckhard Mayer, Marco Morsolini, Tomás Pulido-Zamudio, Gerald Simonneau, Martin R. Wilkins, John Curram, Neil Davie, Marius M. Hoeper

Research output: Contribution to journalArticle

Abstract

Background In the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase - Stimulator Trial 1 (CHEST-1) study, riociguat improved 6-minute walking distance (6MWD) vs placebo in patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. In this study, the proportion of patients who achieved responder thresholds that correlate with improved outcome in patients with pulmonary arterial hypertension was determined at baseline and at the end of CHEST-1. Methods Patients received placebo or riociguat individually adjusted up to 2.5 mg 3 times a day for 16 weeks. Response criteria were defined as follows: 6MWD increase ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liters/min/m2, pulmonary vascular resistance -5, mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide -5 from 37%, 34%, and 25% at baseline to 58%, 57%, and 50% at Week 16, whereas there was little change in placebo-treated patients (6MWD ≥380 m, 43% vs 44%; World Health Organization functional class I/II, 29% vs 38%; pulmonary vascular resistance -5, 27% vs 26%). Similar changes were observed for thresholds for cardiac index, mixed venous oxygen saturation, N-terminal pro-brain natriuretic peptide, and right atrial pressure. Conclusions In this exploratory analysis, riociguat increased the proportion of patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy achieving criteria defining a positive response to therapy.

Original languageEnglish
Pages (from-to)348-355
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • chronic thromboembolic pulmonary hypertension
  • responder threshold criteria
  • riociguat
  • soluble guanylate cyclase stimulator
  • treatment response

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery
  • Medicine(all)

Fingerprint Dive into the research topics of 'Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study'. Together they form a unique fingerprint.

  • Cite this

    D'Armini, A. M., Ghofrani, H. A., Kim, N. H., Mayer, E., Morsolini, M., Pulido-Zamudio, T., Simonneau, G., Wilkins, M. R., Curram, J., Davie, N., & Hoeper, M. M. (2015). Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study. Journal of Heart and Lung Transplantation, 34(3), 348-355. https://doi.org/10.1016/j.healun.2015.02.003