THERAPY-HYBRID-BPA Trial

NCT04600492 | Unknown Phase 2 DMC

• 1 other identifier: Riociguat-CTEPH
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Hypertension, Pulmonary

Keywords

Chronic Thromboembolic Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Peak CI change

  Change in Peak CI during the cardiopulmonary exercise test (CPET)

  from baseline to 16 weeks

Study Arms (2)

Active Comparator: Active drug group Riociguat

ACTIVE COMPARATOR

Riociguat 0.5mg、1.0mg、2.5mg

Drug: Riociguat Oral Tablet

Placebo group

PLACEBO COMPARATOR

Placebo 0.5mg、1.0mg、2.5mg

Drug: Riociguat Oral Tablet

Interventions

Riociguat Oral Tablet DRUG

Take any dose of Riociguat from 0.5mg to 2.5mg, or placebo

Active Comparator: Active drug group Riociguat; Placebo group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Hospital Organization Okayama Medical Center: lead
• Bayer Yakuhin, Ltd.: collaborator

Study Sites (1)

National Hospital Org anization Okayama Medical Center

Okayama, 701-1192, Japan

RECRUITING

Related Publications (7)

• 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.

  PMID: 26320113 BACKGROUND

• 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.

  PMID: 23883377 BACKGROUND

• Mizoguchi 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.

  PMID: 23192917 BACKGROUND

• Kataoka 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.

  PMID: 23132237 BACKGROUND

• Shimokawahara 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.

  PMID: 40714010 DERIVED

• Shimokawahara 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.

  PMID: 37407055 DERIVED

• Shimokawahara 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.

  PMID: 34224432 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

riociguat

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Yutaka Ito

  National Hospital Organization Nagoya Medical Center

  STUDY DIRECTOR

Central Study Contacts

Hiroto Shimokawahara, MD,PhD

CONTACT

+81-86-294-9911; hiroto.shimokk@gmail.com

Yutaka Ito

CONTACT

+81-52-951-1111; study.office@nnh.go.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: A double-blind, placebo-controlled study
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A double-blind, placebo-controlled study

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 23, 2020
• Study Start: October 16, 2020
• Primary Completion: September 30, 2023
• Study Completion: January 28, 2025
• Last Updated: October 23, 2020

Record last verified: 2020-10

Locations

JP (1)