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

7 Citations (Scopus)

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

Fingerprint

Pulmonary Hypertension
Walking
Endarterectomy
Brain Natriuretic Peptide
Placebos
Vascular Resistance
Therapeutics
Oxygen
Lung
Atrial Pressure
riociguat

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)

Cite this

Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study. / D'Armini, Andrea M.; Ghofrani, Hossein Ardeschir; Kim, Nick H.; Mayer, Eckhard; Morsolini, Marco; Pulido-Zamudio, Tomás; Simonneau, Gerald; Wilkins, Martin R.; Curram, John; Davie, Neil; Hoeper, Marius M.

In: Journal of Heart and Lung Transplantation, Vol. 34, No. 3, 01.03.2015, p. 348-355.

Research output: Contribution to journalArticle

D'Armini, AM, Ghofrani, HA, Kim, NH, Mayer, E, Morsolini, M, Pulido-Zamudio, T, Simonneau, G, Wilkins, MR, Curram, J, Davie, N & Hoeper, MM 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, vol. 34, no. 3, pp. 348-355. https://doi.org/10.1016/j.healun.2015.02.003
D'Armini, Andrea M. ; Ghofrani, Hossein Ardeschir ; Kim, Nick H. ; Mayer, Eckhard ; Morsolini, Marco ; Pulido-Zamudio, Tomás ; Simonneau, Gerald ; Wilkins, Martin R. ; Curram, John ; Davie, Neil ; Hoeper, Marius M. / Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study. In: Journal of Heart and Lung Transplantation. 2015 ; Vol. 34, No. 3. pp. 348-355.
@article{e08dcbf9faa9463caa91ca970a2bce5d,
title = "Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study",
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.",
keywords = "chronic thromboembolic pulmonary hypertension, responder threshold criteria, riociguat, soluble guanylate cyclase stimulator, treatment response",
author = "D'Armini, {Andrea M.} and Ghofrani, {Hossein Ardeschir} and Kim, {Nick H.} and Eckhard Mayer and Marco Morsolini and Tom{\'a}s Pulido-Zamudio and Gerald Simonneau and Wilkins, {Martin R.} and John Curram and Neil Davie and Hoeper, {Marius M.}",
year = "2015",
month = "3",
day = "1",
doi = "10.1016/j.healun.2015.02.003",
language = "English",
volume = "34",
pages = "348--355",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study

AU - D'Armini, Andrea M.

AU - Ghofrani, Hossein Ardeschir

AU - Kim, Nick H.

AU - Mayer, Eckhard

AU - Morsolini, Marco

AU - Pulido-Zamudio, Tomás

AU - Simonneau, Gerald

AU - Wilkins, Martin R.

AU - Curram, John

AU - Davie, Neil

AU - Hoeper, Marius M.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

KW - chronic thromboembolic pulmonary hypertension

KW - responder threshold criteria

KW - riociguat

KW - soluble guanylate cyclase stimulator

KW - treatment response

UR - http://www.scopus.com/inward/record.url?scp=84925301583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925301583&partnerID=8YFLogxK

U2 - 10.1016/j.healun.2015.02.003

DO - 10.1016/j.healun.2015.02.003

M3 - Article

C2 - 25813765

AN - SCOPUS:84925301583

VL - 34

SP - 348

EP - 355

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

IS - 3

ER -