Clinical trial NCT00910429: BAY63-2521 - Long-term Extension Study in Patients With Chronic Thromboembolic Pulmonary Hypertension
Official title: Long-term Extension, Multicentre, Multi-international Study to Evaluate the Safety and Tolerability of Oral BAY63-2521 (1mg, 1.5 mg, 2.0 mg, 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 Hypertension
PH
soluble Guanylate Cyclase Stimulator
sGC
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-05-29
Enrollment: 237
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients who have completed the 16 weeks treatment of the CHEST-1 trial (study number 11348) will be asked to participate in this long term extension study with BAY63-2521. The aim of the long term study is to collect additional information to evaluate the safety and tolerability of BAY63-2521. Patients will be treated with open label medication on their individual optimal dose between 0,5 mg - 2,5 mg tid.


Eligibility criteria: Inclusion Criteria:

* Patients who have completed 16 weeks of treatment in the double blind trial CHEST 1

Exclusion Criteria:

* Patients who have an ongoing serious adverse event from CHEST 1 that is assessed as related to BAY63-2521 are not allowed to participate in the extension trial

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years
measure: Number of Participants With Death
timeFrame: From baseline to end of safety follow-up visit, up to 10 years (1 month more than End of study visit)
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
timeFrame: From baseline to Termination visit, up to 10 years
measure: Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change From Baseline of Hemoglobin in Hematology and Coagulation
timeFrame: From baseline to Termination visit, up to 10 years
measure: Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
timeFrame: From baseline to Termination visit, up to 10 years
measure: Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change From Baseline of Urate in Clinical Chemistry
timeFrame: From baseline to Termination visit, up to 10 years
Other outcomes:
measure: Change of Systolic Blood Pressure (SBP)
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of Diastolic Blood Pressure (DBP)
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of Heart Rate
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of Weight
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of Oxygen Saturation (SaO2)
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of Arterial Partial Oxygen Pressure (PaO2)
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
timeFrame: From baseline to Termination visit, up to 10 years
measure: Change of RR Duration From Electrocardiogram (ECG)
timeFrame: From baseline to Month 48
measure: Change of PR Duration From ECG
timeFrame: From baseline to Month 48
measure: Change of QRS Duration From ECG
timeFrame: From baseline to Month 48
measure: Change of QT Duration in ECG
timeFrame: From baseline to Month 48
measure: Change in Six-minute Walking Distance (6MWD) Test
timeFrame: From baseline to End of study visit, up to 10 years
measure: Change in Pulmonary Vascular Resistance (PVR)
timeFrame: From baseline to Month 45 and Month 48
measure: Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
timeFrame: From baseline to End of study visit, up to 10 years
measure: Change in World Health Organization (WHO) Functional Class
timeFrame: From baseline to End of study visit, up to 10 years
measure: Number of Participants With Clinical Worsening
timeFrame: From baseline to End of study visit, up to 10 years
measure: Incidence of Clinical Worsening Events Per 100 Person Years
timeFrame: From baseline to End of study visit, up to 10 years
measure: Change From Baseline in Borg CR 10 Scale
timeFrame: From baseline to Week 12
measure: Change in Score of EQ-5D Questionnaire
timeFrame: From baseline to End of study visit, up to 10 years
measure: Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire
timeFrame: From baseline to End of study visit, up to 10 years
Locations:
city: La Jolla
country: United States
state: California
city: Sacramento
country: United States
state: California
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: 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: Beijing
country: China
city: Beijing
country: China
city: Shanghai
country: China
city: Praha 2
country: Czechia
city: Aarhus N
country: Denmark
city: Brest
country: France
city: Le Kremlin Bicetre Cedex
country: France
city: Rouen
country: France
city: Vandoeuvre Les Nancy
country: France
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: 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: Petach Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus
city: Pavia
country: Italy
state: Lombardia
city: Nagoya
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: Bunkyo-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: Mexico D.F.
country: Mexico
city: Querétaro
country: Mexico
city: Krakow
country: Poland
city: Otwock
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte - Hospital Santa Maria
city: Novosibirsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Bratislava 37
country: Slovakia
city: Barcelona
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
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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: Benza RL, Ghofrani HA, Grunig E, Hoeper MM, Jansa P, Jing ZC, Kim NH, Langleben D, Simonneau G, Wang C, Busse D, Meier C, Ghio S. Effect of riociguat on right ventricular function in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant. 2021 Oct;40(10):1172-1180. doi: 10.1016/j.healun.2021.06.020. Epub 2021 Jul 10.
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.
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: 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.