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Pulmonary HypertensionPhase 3CHEST-1NCT00855465

A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH.

A Phase 3 study testing Riociguat (Adempas, BAY63-2521) in people with Pulmonary Hypertension, run by Bayer at 89 sites in 26 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Pulmonary Hypertension
What is being tested?
Riociguat (Adempas, BAY63-2521)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
262 participants
Where
89 sitesin 26 countries
Study dates
23 Feb 2009to 27 Jun 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

89 sites in 26 countries.

89 sites in 26 countries

Japan15 sites

  • Study site

    Bunkyo-ku, Tokyo, 113-8655

  • Study site

    Chiba, 260-8677

  • Study site

    Fujisawa, Kanagawa, 251-0041

  • Study site

    Fukuoka, 812-8582

  • Study site

    Kawasaki, Kanagawa, 216-8511

  • Study site

    Kitakyushu, Fukuoka, 802-8555

  • Study site

    Komatsu, Ishikawa-ken, 923-8560

  • Study site

    Mitaka, Tokyo, 181-8611

  • Study site

    Nagoya, Aichi-ken, 467-8602

  • Study site

    Sendai, Miyagi, 980-8574

  • Study site

    Seto, Aichi-ken, 489-8642

  • Study site

    Shinjuku-ku, Tokyo, 160-8582

  • Study site

    Shinjuku-ku, Tokyo, 162-8655

  • Study site

    Suita, Osaka, 565-8565

  • Study site

    Suwa, Nagano, 392-8510

Other trials in Japan

Germany12 sites

  • Study site

    Cologne, North Rhine-Westphalia, 50924

  • Study site

    Dresden, Saxony, 01307

  • Study site

    Giessen, Hesse, 35392

  • Study site

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Study site

    Hamburg, 20251

  • Study site

    Hanover, Lower Saxony, 30625

  • Study site

    Heidelberg, Baden-Wurttemberg, 69120

  • Study site

    Heidelberg, Baden-Wurttemberg, 69126

  • Study site

    Homburg, Saarland, 66421

  • Study site

    Leipzig, Saxony, 04103

  • Study site

    München, Bavaria, 81377

  • Study site

    Würzburg, Bavaria, 97074

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United States9 sites

  • Study site

    Baltimore, Maryland, 21205

  • Study site

    Boston, Massachusetts, 02118

  • Study site

    Cleveland, Ohio, 44195

  • Study site

    Columbus, Ohio, 43221

  • Study site

    Dallas, Texas, 75390

  • Study site

    Iowa City, Iowa, 52242

  • Study site

    La Jolla, California, 92093

  • Study site

    Miami, Florida, 33136

  • Study site

    Sacramento, California, 95817

Other trials in United States

France8 sites

  • Study site

    Brest, F-29609

  • Study site

    Caen, 14033

  • Hopital Antoine Beclere

    Clamart, 92141

  • Study site

    Lille, 59037

  • Study site

    Nice, 06200

  • Study site

    Pessac, 33604

  • Study site

    Rouen, 76031

  • Study site

    Vandœuvre-lès-Nancy, F-54500

Other trials in France

Canada5 sites

  • Study site

    Calgary, Alberta, T1Y 6J4

  • Study site

    London, Ontario, N6A 4G5

  • Study site

    Montreal, Quebec, H3T 1E2

  • Study site

    Ottawa, Ontario, K1Y 4W7

  • Study site

    Toronto, Ontario, M5G 2N2

Other trials in Canada

China5 sites

  • Study site

    Beijing, 100020

  • Study site

    Beijing, 100037

  • Study site

    Beijing, 100038

  • Study site

    Qingdao, Shandong, 266003

  • Study site

    Shanghai, 200433

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Mexico4 sites

  • Study site

    Mexico City, 14080

  • Study site

    Monterrey, Nuevo León, 64020

  • Study site

    Monterrey, Nuevo León, 64460

  • Study site

    Querétaro, 38000

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Brazil3 sites

  • Study site

    Porto Alegre, Rio Grande do Sul, 90020 090

  • Study site

    Rio de Janeiro, 21941-913

  • Study site

    São Paulo, São Paulo, 04020-050

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Turkey (Türkiye)3 sites

  • Study site

    Ankara

  • Study site

    Istanbul, 34093

  • Study site

    Izmir, 35040

Other trials in Turkey (Türkiye)

United Kingdom3 sites

  • Study site

    Cambridge, Cambridgeshire, CB23 3RE

  • Study site

    Glasgow, West Dunbartonshire, G81 4DY

  • Study site

    London, W12 0HS

Other trials in United Kingdom

Austria2 sites

  • Study site

    Innsbruck, 6020

  • Study site

    Vienna, 1090

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Belgium2 sites

  • Study site

    Bruxelles - Brussel, 1070

  • Study site

    Leuven, 3000

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Poland2 sites

  • Study site

    Krakow, 31-202

  • Study site

    Otwock, 05-400

Other trials in Poland

Russia2 sites

  • Study site

    Novosibirsk, 630055

  • Study site

    Saint Petersburg, 197341

Other trials in Russia

South Korea2 sites

  • Study site

    Seoul, 06351

  • Study site

    Seoul, 138-736

Other trials in South Korea

Spain2 sites

  • Study site

    Barcelona, 08036

  • Study site

    Madrid, 28041

Other trials in Spain

Argentina1 site

  • Study site

    Corrientes, 3400

Other trials in Argentina

Australia1 site

  • Study site

    Prahran, Victoria, 3181

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Czechia1 site

  • Vseobecna fakultni nemocnice

    Prague, 12808

Other trials in Czechia

Denmark1 site

  • Study site

    Aarhus N, 8200

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Italy1 site

  • Study site

    Pavia, Lombardy, 27100

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Netherlands1 site

  • Study site

    Amsterdam, 1081 HV

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Portugal1 site

  • Study site

    Coimbra, 3000-075

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Slovakia1 site

  • Study site

    Bratislava, 833 48

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Switzerland1 site

  • Study site

    Zurich, 8091

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Taiwan1 site

  • Study site

    Taipei, 100

Other trials in Taiwan

About this study

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)

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).

Read the detailed description

Adverse event data will be covered in Adverse events section.

Being tested
Riociguat (Adempas, BAY63-2521), Placebo
Keywords
Chronic thromboembolic pulmonary hypertension, PH, soluble Guanylate Cyclase Stimulator, sGC
Medical subject headings
Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Riociguat (Adempas, BAY63-2521)Drug

    BAY63-2521: 1 mg tid - 2,5 mg tid orally for 16 weeks.

  • PlaceboDrug

    Matching Placebo tid orally for 16 weeks

Study groups in NCT00855465
Study groupRoleWhat they receive
Riociguat (Adempas, BAY63-2521)_individual dose titrationExperimentalParticipants 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
Receives: Drug: Riociguat (Adempas, BAY63-2521)
PlaceboPlacebo comparatorParticipants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16

    6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.

    Measured: Baseline and week 16

Secondary outcomes (7)

  1. Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16

    The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80*(PAPmean - PCWP)/CO

    Measured: Baseline and week 16

  2. N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16

    N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.

    Measured: Baseline and week 16

  3. World Health Organization (WHO) Functional Class - Change From Baseline to Week 16

    The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH.

    Measured: Baseline and week 16

  4. Percentage of Participants With Clinical Worsening

    The combined endpoint "time to clinical worsening", made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; rescue endarterectomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH.

    Measured: At week 16

  5. Borg CR 10 Scale - Change From Baseline to Week 16

    The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal").

    Measured: Baseline and week 16

  6. EQ-5D Utility Score - Change From Baseline to Week 16

    EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).

    Measured: Baseline and week 16

  7. Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16

    The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst).

    Measured: Baseline and week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2009 (estimated)
  2. Study start23 Feb 2009
  3. Primary completion27 Jun 2012
  4. Study completion27 Jun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
262 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00855465
Sponsor's protocol ID
11348
Other IDs
2007-000072-16
Acronym
CHEST-1
Status last verified
Nov 2023
First submitted
15 Dec 2008
Last updated
21 Nov 2023
Data monitoring committee
Yes

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.

    PubMed 23883377

  • 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.

    PubMed 23883383

  • 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.

    PubMed 27067478

  • 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.

    PubMed 27326239

  • 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.

    PubMed 27263466

  • 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.

    PubMed 26910470

  • 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.

    PubMed 27106231

  • 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.

    PubMed 34848133

  • 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.

    PubMed 35256218

  • 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.

    PubMed 28011757

  • 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.

    PubMed 27162632

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Riociguat (Adempas, BAY63-2521) in people with Pulmonary Hypertension, run by Bayer at 89 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 89 sites in Japan, Germany, United States, France, Canada and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16 (time frame: Baseline and week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00855465, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2023; AzTrials last refreshed its copy on 8 Nov 2026.

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