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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00855465




Registration number
NCT00855465
Ethics application status
Date submitted
15/12/2008
Date registered
4/03/2009
Date last updated
21/11/2023

Titles & IDs
Public title
A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH.
Scientific 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)
Secondary ID [1] 0 0
2007-000072-16
Secondary ID [2] 0 0
11348
Universal Trial Number (UTN)
Trial acronym
CHEST-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Placebo

Experimental: Riociguat (Adempas, BAY63-2521)_individual dose titration - Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks

Placebo comparator: Placebo - Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks


Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
BAY63-2521: 1 mg tid - 2,5 mg tid orally for 16 weeks.

Treatment: Drugs: Placebo
Matching Placebo tid orally for 16 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16
Timepoint [1] 0 0
Baseline and week 16
Secondary outcome [1] 0 0
Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16
Timepoint [1] 0 0
Baseline and week 16
Secondary outcome [2] 0 0
N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16
Timepoint [2] 0 0
Baseline and week 16
Secondary outcome [3] 0 0
World Health Organization (WHO) Functional Class - Change From Baseline to Week 16
Timepoint [3] 0 0
Baseline and week 16
Secondary outcome [4] 0 0
Percentage of Participants With Clinical Worsening
Timepoint [4] 0 0
At week 16
Secondary outcome [5] 0 0
Borg CR 10 Scale - Change From Baseline to Week 16
Timepoint [5] 0 0
Baseline and week 16
Secondary outcome [6] 0 0
EQ-5D Utility Score - Change From Baseline to Week 16
Timepoint [6] 0 0
Baseline and week 16
Secondary outcome [7] 0 0
Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16
Timepoint [7] 0 0
Baseline and week 16

Eligibility
Key inclusion criteria
* Male and female patients with CTEPH either inoperable or with persistent or recurrent PH after surgery.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* All types of pulmonary hypertension except subtypes 4.1 and 4.2 of the Venice Clinical Classification of Pulmonary Hypertension.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/02/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/06/2012
Sample size
Target
Accrual to date
Final
262
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
- Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Corrientes
Country [9] 0 0
Austria
State/province [9] 0 0
Innsbruck
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles - Brussel
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Brazil
State/province [13] 0 0
Rio Grande Do Sul
Country [14] 0 0
Brazil
State/province [14] 0 0
Sao Paulo
Country [15] 0 0
Brazil
State/province [15] 0 0
Rio de Janeiro
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
China
State/province [19] 0 0
Shandong
Country [20] 0 0
China
State/province [20] 0 0
Beijing
Country [21] 0 0
China
State/province [21] 0 0
Shanghai
Country [22] 0 0
Czechia
State/province [22] 0 0
Praha 2
Country [23] 0 0
Denmark
State/province [23] 0 0
Aarhus N
Country [24] 0 0
France
State/province [24] 0 0
Brest
Country [25] 0 0
France
State/province [25] 0 0
Caen
Country [26] 0 0
France
State/province [26] 0 0
Clamart Cedex
Country [27] 0 0
France
State/province [27] 0 0
Lille Cedex
Country [28] 0 0
France
State/province [28] 0 0
Nice
Country [29] 0 0
France
State/province [29] 0 0
Pessac
Country [30] 0 0
France
State/province [30] 0 0
Rouen
Country [31] 0 0
France
State/province [31] 0 0
Vandoeuvre Les Nancy
Country [32] 0 0
Germany
State/province [32] 0 0
Baden-Württemberg
Country [33] 0 0
Germany
State/province [33] 0 0
Bayern
Country [34] 0 0
Germany
State/province [34] 0 0
Hessen
Country [35] 0 0
Germany
State/province [35] 0 0
Mecklenburg-Vorpommern
Country [36] 0 0
Germany
State/province [36] 0 0
Niedersachsen
Country [37] 0 0
Germany
State/province [37] 0 0
Nordrhein-Westfalen
Country [38] 0 0
Germany
State/province [38] 0 0
Saarland
Country [39] 0 0
Germany
State/province [39] 0 0
Sachsen
Country [40] 0 0
Germany
State/province [40] 0 0
Hamburg
Country [41] 0 0
Italy
State/province [41] 0 0
Lombardia
Country [42] 0 0
Japan
State/province [42] 0 0
Aichi
Country [43] 0 0
Japan
State/province [43] 0 0
Fukuoka
Country [44] 0 0
Japan
State/province [44] 0 0
Ishikawa
Country [45] 0 0
Japan
State/province [45] 0 0
Kanagawa
Country [46] 0 0
Japan
State/province [46] 0 0
Miyagi
Country [47] 0 0
Japan
State/province [47] 0 0
Nagano
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Japan
State/province [50] 0 0
Chiba
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul
Country [52] 0 0
Mexico
State/province [52] 0 0
Nuevo Leon
Country [53] 0 0
Mexico
State/province [53] 0 0
Mexico D.F.
Country [54] 0 0
Mexico
State/province [54] 0 0
Querétaro
Country [55] 0 0
Netherlands
State/province [55] 0 0
Amsterdam
Country [56] 0 0
Poland
State/province [56] 0 0
Krakow
Country [57] 0 0
Poland
State/province [57] 0 0
Otwock
Country [58] 0 0
Portugal
State/province [58] 0 0
Coimbra
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Novosibirsk
Country [60] 0 0
Russian Federation
State/province [60] 0 0
St. Petersburg
Country [61] 0 0
Slovakia
State/province [61] 0 0
Bratislava 37
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Switzerland
State/province [64] 0 0
Zürich
Country [65] 0 0
Taiwan
State/province [65] 0 0
Taipei
Country [66] 0 0
Turkey
State/province [66] 0 0
Ankara
Country [67] 0 0
Turkey
State/province [67] 0 0
Istanbul
Country [68] 0 0
Turkey
State/province [68] 0 0
Izmir
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Cambridgeshire
Country [70] 0 0
United Kingdom
State/province [70] 0 0
West Dunbartonshire
Country [71] 0 0
United Kingdom
State/province [71] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT00855465
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00855465