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THERAPY-HYBRID-BPA Trial

Primary Purpose

Hypertension, Pulmonary

Status

Recruiting

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Riociguat Oral Tablet

About this trial

This is an interventional supportive care trial for Hypertension, Pulmonary focused on measuring Chronic Thromboembolic Pulmonary Hypertension

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

National Hospital Org anization Okayama Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Comparator: Active drug group Riociguat

Placebo group

Arm Description

Riociguat 0.5mg、1.0mg、2.5mg

Placebo 0.5mg、1.0mg、2.5mg

Outcomes

Primary Outcome Measures

Peak CI change

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

Secondary Outcome Measures

Full Information

NCT ID

NCT04600492

First Posted

October 19, 2020

Last Updated

October 22, 2020

Sponsor

National Hospital Organization Okayama Medical Center

Collaborators

Bayer Yakuhin, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04600492

Brief Title

THERAPY-HYBRID-BPA Trial

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Recruiting

Study Start Date

October 16, 2020 (Anticipated)

Primary Completion Date

September 30, 2023 (Anticipated)

Study Completion Date

January 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Hospital Organization Okayama Medical Center

Collaborators

Bayer Yakuhin, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension, Pulmonary

Keywords

Chronic Thromboembolic Pulmonary Hypertension

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

A double-blind, placebo-controlled study

Masking

ParticipantInvestigator

Masking Description

A double-blind, placebo-controlled study

Allocation

Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active Comparator: Active drug group Riociguat

Arm Type

Active Comparator

Arm Description

Riociguat 0.5mg、1.0mg、2.5mg

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Placebo 0.5mg、1.0mg、2.5mg

Intervention Type

Drug

Intervention Name(s)

Riociguat Oral Tablet

Intervention Description

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

Primary Outcome Measure Information:

Title

Peak CI change

Description

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

Time Frame

from baseline to 16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hiroto Shimokawahara, MD,PhD

Phone

+81-86-294-9911

hiroto.shimokk@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yutaka Ito

Phone

+81-52-951-1111

Ext

2493

study.office@nnh.go.jp

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yutaka Ito

Organizational Affiliation

National Hospital Organization Nagoya Medical Center

Official's Role

Study Director

Facility Information:

Facility Name

National Hospital Org anization Okayama Medical Center

City

Okayama

ZIP/Postal Code

701-1192

Country

Japan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hiroto Shimokawahara, MD,PhD

Phone

+81-86-294-9911

hiroto.shimokk@gmail.com

First Name & Middle Initial & Last Name & Degree

Miki Yanagihara

Phone

+81-86-294-9911

okmc-iec@nifty.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

26320113

Citation

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.

Results Reference

background

PubMed Identifier

23883377

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.

Results Reference

background

PubMed Identifier

23192917

Citation

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.

Results Reference

background

PubMed Identifier

23132237

Citation

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.

Results Reference

background

PubMed Identifier

34224432

Citation

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.

Results Reference

derived

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THERAPY-HYBRID-BPA Trial

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