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Signs and Symptoms of Chest Diseases |

Riociguat for the Treatment of Inoperable Chronic Thromboembolic Pulmonary Hypertension: A Randomized, Double-Blind, Placebo-Controlled Study (CHEST-1)

Hossein Ghofrani*, MD; Friedrich Grimminger, MD; Marius Hoeper, MD; Nick Kim, MD; Eckhard Mayer, MD; Dieter Neuser, MD; Janethe Pena, MD; Gerald Simonneau, MD; Martin Wilkins, MD
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Department of Internal Medicine, University Hospital Giessen and Marburg, Giessen, Germany


Chest. 2012;142(4_MeetingAbstracts):1023A. doi:10.1378/chest.1462924
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Abstract

SESSION TYPE: Late-Breaking Abstracts

PRESENTED ON: Tuesday, October 23, 2012 at 04:30 PM - 05:45 PM

PURPOSE: Riociguat is the first member of a novel class of compounds, the soluble guanylate cyclase (sGC) stimulators. With a dual mode of action, it synergizes with endogenous nitric oxide (NO) and also directly stimulates sGC independent of NO availability. Riociguat restores the NO-sGC-cGMP pathway resulting in a significant improvement in pulmonary vascular hemodynamics and an increase in exercise ability. Here, we present results from the Phase III, multicenter, randomized, double-blind, placebo-controlled CHEST-1 study, which investigated the efficacy and safety of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

METHODS: Patients with inoperable CTEPH (as assessed by an independent adjudication committee) or with persisting or recurrent pulmonary hypertension (PH) after pulmonary endarterectomy (PEA), and a mean pulmonary vascular resistance (PVR) >480 dyn·s/cm5 were enrolled in the trial. Treatment with supportive PH therapies was permitted but patients were treatment naïve with regards to pulmonary arterial hypertension-specific therapies. Patients were randomized to either placebo or oral riociguat, which was titrated from a starting dose of 1 mg three times daily (t.i.d.) according to systolic blood pressure (range 0.5-2.5 mg t.i.d.). The primary outcome measure was the change from baseline in 6-minute walking distance after 16 weeks of treatment. Secondary endpoints included change from baseline in PVR, functional class, time to clinical worsening, and safety and tolerability.

RESULTS: The study has enrolled a total of 263 patients. Results will be available and presented at the time of the congress.

CONCLUSIONS: The CHEST-1 study is the largest placebo-controlled trial to date in CTEPH and will assess the therapeutic benefit of the sGC stimulator riociguat.

CLINICAL IMPLICATIONS: At present, no approved pharmacologic therapy exists for CTEPH and as a result there is an urgent unmet need in patients who are not eligible for PEA, or who have persistent or recurrent PH after PEA.

DISCLOSURE: Hossein Ghofrani: Grant monies (from sources other than industry): Hossein A. Ghofrani has received sponsored grants over the past 3 years from the German Research Foundation, Excellence Cluster Cardiopulmonary Research and Germany Ministry for Education and Research, Grant monies (from industry related sources): Hossein A. Ghofrani has received industry-sponsored grants over the past 3 years from Bayer HealthCare AG, Aires, Encysive/Pfizer and Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Hossein A. Ghofrani has relationships with the following drug companies: Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Novartis and GlaxoSmithKline

Friedrich Grimminger: Consultant fee, speaker bureau, advisory committee, etc.: Friedrich Grimminger has relationships with Bayer AG

Marius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: Marius Hoeper has relationships with the following drug companies: Actelion, Bayer, Gilead, GlaxoSmithKline, Lilly, Novartis and Pfizer

Nick Kim: Grant monies (from industry related sources): Nick H. Kim has received industry related grant monies from the following drug companies: Actelion, Gilead and United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Nick H. Kim has relationships with the following drug companies: Bayer (consultant), Gilead, United Therapeutics (advisory meeting)

Eckhard Mayer: Consultant fee, speaker bureau, advisory committee, etc.: Eckhard Mayer has relationships with the following drug companies: Bayer Schering, Pfizer, Actelion

Dieter Neuser: Employee: Dieter Neuser is an employee of Bayer Pharma AG

Janethe Pena: Employee: Janethe Pena is an employee of Bayer HealthCare

Gerald Simonneau: University grant monies: Gerald Simonneau has received university grant monies from the following drug companies: Actelion, Bayer, GlaxoSmithKline, Lilly, Novartis and Pfizer, Grant monies (from industry related sources): Gerald Simonneau has received industry related grant monies from the following drug companies: Actelion, Bayer, GlaxoSmithKline, Lilly, Novartis and Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Gerald Simonneau has relationships with the following drug companies: Actelion, Bayer, GlaxoSmithKline, Lilly, Novartis and Pfizer

Martin Wilkins: Grant monies (from industry related sources): Martin Wilkins has received grant monies from Bayer, Consultant fee, speaker bureau, advisory committee, etc.: Martin Wilkins is a Chair on a research abstract panel for Bayer

Riociguat is an investigational new drug currently in process for registration submission to health authorities, after successful finalisation of an RCT in patients with PAH.

Department of Internal Medicine, University Hospital Giessen and Marburg, Giessen, Germany

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