Hypertension, PulmonaryPhase 2NCT04600492
THERAPY-HYBRID-BPA Trial
A Phase 2 study testing Riociguat Oral Tablet in people with Hypertension, Pulmonary, run by National Hospital Organization Okayama Medical Center at 1 site in Japan.
Trial summary
Riociguat could improve the exercise capacity and residual symptoms in patients with chronic thromboembolic pulmonary hypertension (CTEPH) even after normalization of pulmonary arterial pressure by balloon pulmonary angioplasty (BPA). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hypertension, Pulmonary
- What is being tested?
- Riociguat Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteJapan
- Study dates
- 16 Oct 2020to 28 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who meet CTEPH diagnostic criteria (complying with 2017 Japanese Cardiovascular Society Guidelines diagnostic criteria)
- Patients with diagnosed as a contraindication of pulmonary endarterectomy by an experienced surgeon in the central diagnosis
- Patients who were adjusted to reach the appropriate dose of riociguat within 8 weeks and were able to continue riociguat thereafter
- Patients who underwent BPA once or more after the dose adjustment of riociguat
- Patients who have been able to continue taking the same dose of riociguat for more than 3 months
- Patients who can obtain written informed consent from the patients and legal representatives
Show all 10Show fewer
- Patients with WHO functional class II or III at the time of the allocation
- Over the age of 18 and under 85 at the time of obtaining informed consent
- Patients with the resting CI value of less than 3.0 L/min/m2 in the right heart catheterization test immediately before the allocation
- Patients with the mean pulmonary artery pressure less than 25 mmHg in a right heart catheterization test immediately before the allocation
Who cannot join
- Patients who are eligible for pulmonary endarterectomy (PEA)
- Patients with pulmonary hypertension other than class 4 by NICE classification
- Patients having difficulty in performing cardiopulmonary exercise test (CPET)
- Patients with severe right heart failure requiring cardiotonic drugs
- Patients with severe heart disease
- Patients with severe liver damage
Show all 15Show fewer
- Patients with systolic blood pressure less than 90 mmHg at the screening
- Patients with shunt disease
- Patients with severe renal dysfunction (CCr < 15 mL/min) requiring hemodialysis
- Patients with life expectancy less than 2 years
- Being pregnant or lactating
- Patients who are contraindicated for riociguat
- Patients using other unlicensed drugs
- Patients who used pulmonary vasodilators within 4 weeks after obtaining the informed consent of the right heart catheterization test.
- Patients whom the investigator determines that the participation in this study is inappropriate
Trial locations and contacts
1 site in 1 country.
Japan1 site, 1 recruiting
- Recruiting
National Hospital Org anization Okayama Medical Center
Okayama, 701-1192
Hiroto Shimokawahara, MD,PhD, +81-86-294-9911, hiroto.shimokk@gmail.com
Miki Yanagihara, +81-86-294-9911, okmc-iec@nifty.com
About this study
Official title: The Effect of Riociguat for Peak Cardiac Index on Cardiopulmonary Exercise Test in CTEPH Patients After Normalization of Pulmonary Artery Pressure by Combination Treatment of Riociguat and Balloon Pulmonary Angioplasty
Riociguat could improve the exercise capacity and residual symptoms in patients with chronic thromboembolic pulmonary hypertension (CTEPH) even after normalization of pulmonary arterial pressure by balloon pulmonary angioplasty (BPA). This randomized controlled trial study aimed to clarify whether the improvement of peak cardiac index (CI) during exercise maintains or not between the riociguat continued group and the riociguat discontinued group.
Read the detailed description
CTEPH is a disease that causes progressive pulmonary hypertension due to stenoses or occlusions in the pulmonary artery due to an organized thrombus. And this is a disease that results in right heart failure and death unless early diagnosis and appropriate treatment are performed. Pulmonary endarterectomy (PEA), which surgically removes the intimal thrombus, has been established as the treatment of choice for CTEPH. In the AHA/ACC guideline and ESC guideline, PEA for CTEPH is class IC (1). In 2014, a soluble guanylate cyclase stimulant (generic name: riociguat), which is one of the therapeutic agents for pulmonary hypertension, was approved for patients with CTEPH who are ineligible for PEA, and residual pulmonary hypertension after PEA (2). In addition, it has been reported that BPA, which is a catheter interventional treatment, is also effective to improve hemodynamics in inoperable patients with CTEPH (3, 4). However, some patients have residual symptoms such as dyspnea on exertion even after normalization in hemodynamics by BPA. A randomized control study should be done to confirm the necessary of continuation of riociguat for such patients.
- Conditions
- Hypertension, Pulmonary
- Being tested
- Riociguat Oral Tablet
- Keywords
- Chronic Thromboembolic Pulmonary Hypertension
- 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 Oral TabletDrug
Take any dose of Riociguat from 0.5mg to 2.5mg, or placebo
| Study group | Role | What they receive |
|---|---|---|
| Active Comparator: Active drug group Riociguat | Active comparator | Riociguat 0.5mg、1.0mg、2.5mg Receives: Drug: Riociguat Oral Tablet |
| Placebo group | Placebo comparator | Placebo 0.5mg、1.0mg、2.5mg Receives: Drug: Riociguat Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak CI change
Change in Peak CI during the cardiopulmonary exercise test (CPET)
Measured: from baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2020
- Study start16 Oct 2020 (estimated)
- Primary completion30 Sep 2023 (estimated)
- Study completion28 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A double-blind, placebo-controlled study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Hospital Organization Okayama Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer Yakuhin, Ltd.
- Responsible party
- Sponsor
- Investigators
- Yutaka Ito, Study director, National Hospital Organization Nagoya Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04600492
- Sponsor's protocol ID
- Riociguat-CTEPH
- Status last verified
- Oct 2020
- First submitted
- 19 Oct 2020
- Last updated
- 23 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M; ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. No abstract available.
PubMed 26320113Ghofrani 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 23883377Mizoguchi H, Ogawa A, Munemasa M, Mikouchi H, Ito H, Matsubara H. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv. 2012 Dec;5(6):748-55. doi: 10.1161/CIRCINTERVENTIONS.112.971077. Epub 2012 Nov 27.
PubMed 23192917Kataoka M, Inami T, Hayashida K, Shimura N, Ishiguro H, Abe T, Tamura Y, Ando M, Fukuda K, Yoshino H, Satoh T. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv. 2012 Dec;5(6):756-62. doi: 10.1161/CIRCINTERVENTIONS.112.971390. Epub 2012 Nov 6.
PubMed 23132237Shimokawahara H, Nishizaki M, Inami T, Kubota K, Taniguchi Y, Miyagi A, Kikuchi H, Goda A, Miyanaga S, Hashimoto H, Saito AM, Sekimizu M, Matsubara H. Effect of riociguat on exercise following balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension in Japan (THERAPY-HYBRID-BPA): a multicentre, double-blind, randomised, controlled, phase 4 trial. Lancet Respir Med. 2025 Sep;13(9):789-799. doi: 10.1016/S2213-2600(25)00127-4. Epub 2025 Jul 23.
PubMed 40714010Shimokawahara H, Inami T, Kubota K, Taniguchi Y, Hashimoto H, Saito AM, Sekimizu M, Matsubara H. Protocol for a multicentre, double-blind, randomised, placebo-controlled trial of riociguat on peak cardiac index during exercise in patients with chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty (THERAPY-HYBRID-BPA trial). BMJ Open. 2023 Jul 5;13(7):e072241. doi: 10.1136/bmjopen-2023-072241.
PubMed 37407055Shimokawahara H, Ogawa A, Matsubara H. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: advances in patient and lesion selection. Curr Opin Pulm Med. 2021 Sep 1;27(5):303-310. doi: 10.1097/MCP.0000000000000797.
PubMed 34224432
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Riociguat for Peak Cardiac Index on Cardiopulmonary Exercise Test in CTEPH Patients After Normalization of Pulmonary Artery Pressure by Combination Treatment of Riociguat and Balloon Pulmonary Angioplasty
- ClinicalTrials.gov ID
- NCT04600492
- Acronym / sponsor ID
- Riociguat-CTEPH
- Conditions
- Hypertension, Pulmonary
- Keywords
- Chronic Thromboembolic Pulmonary Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- National Hospital Organization Okayama Medical CenterUniversity, hospital or other
- Collaborators
- Bayer Yakuhin, Ltd.
- Study start
- 16 Oct 2020 (estimated)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 28 Jan 2025 (estimated)
- First posted
- 23 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Riociguat could improve the exercise capacity and residual symptoms in patients with chronic thromboembolic pulmonary hypertension (CTEPH) even after normalization of pulmonary arterial pressure by balloon pulmonary angioplasty (BPA). This randomized controlled trial study aimed to clarify whether the improvement of peak cardiac index (CI) during exercise maintains or not between the riociguat continued group and the riociguat discontinued group.
Detailed description
CTEPH is a disease that causes progressive pulmonary hypertension due to stenoses or occlusions in the pulmonary artery due to an organized thrombus. And this is a disease that results in right heart failure and death unless early diagnosis and appropriate treatment are performed. Pulmonary endarterectomy (PEA), which surgically removes the intimal thrombus, has been established as the treatment of choice for CTEPH. In the AHA/ACC guideline and ESC guideline, PEA for CTEPH is class IC (1). In 2014, a soluble guanylate cyclase stimulant (generic name: riociguat), which is one of the therapeutic agents for pulmonary hypertension, was approved for patients with CTEPH who are ineligible for PEA, and residual pulmonary hypertension after PEA (2). In addition, it has been reported that BPA, which is a catheter interventional treatment, is also effective to improve hemodynamics in inoperable patients with CTEPH (3, 4). However, some patients have residual symptoms such as dyspnea on exertion even after normalization in hemodynamics by BPA. A randomized control study should be done to confirm the necessary of continuation of riociguat for such patients.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A double-blind, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| Active Comparator: Active drug group Riociguat | Active comparator | Drug: Riociguat Oral TabletRiociguat 0.5mg、1.0mg、2.5mg |
| Placebo group | Placebo comparator | Drug: Riociguat Oral TabletPlacebo 0.5mg、1.0mg、2.5mg |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients who meet CTEPH diagnostic criteria (complying with 2017 Japanese Cardiovascular Society Guidelines diagnostic criteria)
- Patients with diagnosed as a contraindication of pulmonary endarterectomy by an experienced surgeon in the central diagnosis
- Patients who were adjusted to reach the appropriate dose of riociguat within 8 weeks and were able to continue riociguat thereafter
- Patients who underwent BPA once or more after the dose adjustment of riociguat
- Patients who have been able to continue taking the same dose of riociguat for more than 3 months
Key exclusion criteria (15 listed)
- Patients who are eligible for pulmonary endarterectomy (PEA)
- Patients with pulmonary hypertension other than class 4 by NICE classification
- Patients having difficulty in performing cardiopulmonary exercise test (CPET)
- Patients with severe right heart failure requiring cardiotonic drugs
- Patients with severe heart disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riociguat Oral TabletTake any dose of Riociguat from 0.5mg to 2.5mg, or placebo | Drug | Active Comparator: Active drug group Riociguat, Placebo group |
Primary outcome
Peak CI change
Time frame: from baseline to 16 weeks
Change in Peak CI during the cardiopulmonary exercise test (CPET)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2020.
- Background: PubMed 26320113Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M; ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. No abstract available.
- Background: PubMed 23883377Ghofrani 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.
- Background: PubMed 23192917Mizoguchi H, Ogawa A, Munemasa M, Mikouchi H, Ito H, Matsubara H. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv. 2012 Dec;5(6):748-55. doi: 10.1161/CIRCINTERVENTIONS.112.971077. Epub 2012 Nov 27.
- Background: PubMed 23132237Kataoka M, Inami T, Hayashida K, Shimura N, Ishiguro H, Abe T, Tamura Y, Ando M, Fukuda K, Yoshino H, Satoh T. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv. 2012 Dec;5(6):756-62. doi: 10.1161/CIRCINTERVENTIONS.112.971390. Epub 2012 Nov 6.
- Derived from this study: PubMed 40714010Shimokawahara H, Nishizaki M, Inami T, Kubota K, Taniguchi Y, Miyagi A, Kikuchi H, Goda A, Miyanaga S, Hashimoto H, Saito AM, Sekimizu M, Matsubara H. Effect of riociguat on exercise following balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension in Japan (THERAPY-HYBRID-BPA): a multicentre, double-blind, randomised, controlled, phase 4 trial. Lancet Respir Med. 2025 Sep;13(9):789-799. doi: 10.1016/S2213-2600(25)00127-4. Epub 2025 Jul 23.
- Derived from this study: PubMed 37407055Shimokawahara H, Inami T, Kubota K, Taniguchi Y, Hashimoto H, Saito AM, Sekimizu M, Matsubara H. Protocol for a multicentre, double-blind, randomised, placebo-controlled trial of riociguat on peak cardiac index during exercise in patients with chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty (THERAPY-HYBRID-BPA trial). BMJ Open. 2023 Jul 5;13(7):e072241. doi: 10.1136/bmjopen-2023-072241.
- Derived from this study: PubMed 34224432Shimokawahara H, Ogawa A, Matsubara H. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: advances in patient and lesion selection. Curr Opin Pulm Med. 2021 Sep 1;27(5):303-310. doi: 10.1097/MCP.0000000000000797.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yutaka Ito study director
National Hospital Organization Nagoya Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riociguat Oral Tablet in people with Hypertension, Pulmonary, run by National Hospital Organization Okayama Medical Center at 1 site in Japan.
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 10 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hiroto Shimokawahara, MD,PhD (+81-86-294-9911, hiroto.shimokk@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak CI change (time frame: from baseline to 16 weeks). 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 NCT04600492, which also lists 7 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 23 Oct 2020.