Clinical trial NCT00855465: A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH.
Official title: Randomized, Double-blind, Placebo-controlled, Multi-centre, Multi-national Study to Evaluate the Efficacy and Safety of Oral BAY63-2521 (1 mg, 1.5 mg, 2 mg, or 2.5 mg Tid) in Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Hypertension
Keywords: Chronic thromboembolic pulmonary hypertension
PH
soluble Guanylate Cyclase Stimulator
sGC
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-03-04
Enrollment: 262
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521, given orally for 16 weeks, in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Detailed description: Adverse event data will be covered in Adverse events section.

Eligibility criteria: Inclusion Criteria:

* Male and female patients with CTEPH either inoperable or with persistent or recurrent PH after surgery.

Exclusion Criteria:

* All types of pulmonary hypertension except subtypes 4.1 and 4.2 of the Venice Clinical Classification of Pulmonary Hypertension.

Primary outcomes:
measure: 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
Secondary outcomes:
measure: Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: World Health Organization (WHO) Functional Class - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Percentage of Participants With Clinical Worsening
timeFrame: At week 16
measure: Borg CR 10 Scale - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: EQ-5D Utility Score - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16
timeFrame: Baseline and week 16
Other outcomes:
measure: All Caused Mortality
timeFrame: At visit 6 (week 16)
measure: Mean Pulmonary Artery Pressure (PAPmean) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Cardiac Index (CI) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Systolic Blood Pressure (SBP) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Diastolic Blood Pressure (DBP) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Heart Rate (HR) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Alanine Aminotransferase (ALT) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Aspartate Aminotransferase (AST) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Alkaline Phosphatase (AP) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Bilirubin - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Creatinine - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Creatinine Clearance - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Creatine Kinase (CK) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Erythrocytes (RBC) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Leukocytes (WBC) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Lymphocytes - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Neutrophils - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Hemoglobin - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Hematocrit - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Potassium - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Urate - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Urea (BUN) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Cystatin C - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Triacylglycerol Lipase - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Arterial Partial Pressure of Carbon Dioxide (PaCO2) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Arterial Partial Oxygen Pressure (PaO2) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Oxygen Saturation (SaO2) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean PR Duration (PRmean) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean QRS Duration (QRSmean) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean QT Duration (QTmean) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean RR Duration (RRmean) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Mean Ventricular Rate (VRmean) - Change From Baseline to Week 16
timeFrame: Baseline and week 16
Locations:
city: La Jolla
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Iowa City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Dallas
country: United States
state: Texas
city: Corrientes
country: Argentina
city: Prahran
country: Australia
state: Victoria
city: Innsbruck
country: Austria
city: Wien
country: Austria
city: Bruxelles - Brussel
country: Belgium
city: Leuven
country: Belgium
city: Porto Alegre
country: Brazil
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Qingdao
country: China
state: Shandong
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Shanghai
country: China
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice
city: Aarhus N
country: Denmark
city: Brest
country: France
city: Caen
country: France
city: Clamart Cedex
country: France
facility: Hopital Antoine Beclere
city: Lille Cedex
country: France
city: Nice
country: France
city: Pessac
country: France
city: Rouen
country: France
city: Vandoeuvre Les Nancy
country: France
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Gießen
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
state: Niedersachsen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Homburg
country: Germany
state: Saarland
city: Dresden
country: Germany
state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Hamburg
country: Germany
city: Pavia
country: Italy
state: Lombardia
city: Nagoya
country: Japan
state: Aichi
city: Seto
country: Japan
state: Aichi
city: Kitakyushu
country: Japan
state: Fukuoka
city: Komatsu
country: Japan
state: Ishikawa
city: Fujisawa
country: Japan
state: Kanagawa
city: Kawasaki
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Suwa
country: Japan
state: Nagano
city: Suita
country: Japan
state: Osaka
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Mitaka
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Mexico D.F.
country: Mexico
city: Querétaro
country: Mexico
city: Amsterdam
country: Netherlands
city: Krakow
country: Poland
city: Otwock
country: Poland
city: Coimbra
country: Portugal
city: Novosibirsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Bratislava 37
country: Slovakia
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Zürich
country: Switzerland
city: Taipei
country: Taiwan
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Glasgow
country: United Kingdom
state: West Dunbartonshire
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013 Jul 25;369(4):319-29. doi: 10.1056/NEJMoa1209657.
citation: Archer SL. Riociguat for pulmonary hypertension--a glass half full. N Engl J Med. 2013 Jul 25;369(4):386-8. doi: 10.1056/NEJMe1306684. No abstract available.
citation: Simonneau G, D'Armini AM, Ghofrani HA, Grimminger F, Jansa P, Kim NH, Mayer E, Pulido T, Wang C, Colorado P, Fritsch A, Meier C, Nikkho S, Hoeper MM. Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016 May;4(5):372-80. doi: 10.1016/S2213-2600(16)30022-4. Epub 2016 Apr 8.
citation: Wang C, Jing ZC, Huang YG, Zhou DX, Liu ZH, Meier C, Nikkho S, Curram J, Zhang P, He JG. Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison. Heart Asia. 2016 May 17;8(1):74-82. doi: 10.1136/heartasia-2015-010712. eCollection 2016.
citation: Ghofrani HA, Humbert M, Langleben D, Schermuly R, Stasch JP, Wilkins MR, Klinger JR. Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension. Chest. 2017 Feb;151(2):468-480. doi: 10.1016/j.chest.2016.05.024. Epub 2016 Jun 2.
citation: Kim DY, Kim HJ, Han KH, Han SY, Heo J, Woo HY, Um SH, Kim YH, Kweon YO, Lim HY, Yoon JH, Lee WS, Lee BS, Lee HC, Ryoo BY, Yoon SK. Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data. Cancer Res Treat. 2016 Oct;48(4):1243-1252. doi: 10.4143/crt.2015.278. Epub 2016 Feb 24.
citation: Kudo M, Ikeda M, Takayama T, Numata K, Izumi N, Furuse J, Okusaka T, Kadoya M, Yamashita S, Ito Y, Kokudo N. Safety and efficacy of sorafenib in Japanese patients with hepatocellular carcinoma in clinical practice: a subgroup analysis of GIDEON. J Gastroenterol. 2016 Dec;51(12):1150-1160. doi: 10.1007/s00535-016-1204-2. Epub 2016 Apr 22.
citation: Benza RL, Boucly A, Farber HW, Frost AE, Ghofrani HA, Hoeper MM, Lambelet M, Rahner C, Bansilal S, Nikkho S, Meier C, Sitbon O. Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study. J Heart Lung Transplant. 2022 Mar;41(3):411-420. doi: 10.1016/j.healun.2021.10.013. Epub 2021 Oct 28.
citation: Benza RL, Farber HW, Frost AE, Ghofrani HA, Corris PA, Lambelet M, Nikkho S, Meier C, Hoeper MM. Application of the REVEAL risk score calculator 2.0 in the CHEST study. Respir Med. 2022 Apr-May;195:106783. doi: 10.1016/j.rmed.2022.106783. Epub 2022 Mar 1.
citation: Kim NH, D'Armini AM, Grimminger F, Grunig E, Hoeper MM, Jansa P, Mayer E, Neurohr C, Simonneau G, Torbicki A, Wang C, Fritsch A, Davie N, Ghofrani HA. Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension. Heart. 2017 Apr;103(8):599-606. doi: 10.1136/heartjnl-2016-309621. Epub 2016 Dec 23.
citation: Saleh S, Becker C, Frey R, Muck W. Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulm Circ. 2016 Mar;6(Suppl 1):S86-96. doi: 10.1086/685404.