THERAPY-HYBRID-BPA Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Riociguat Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A double-blind, placebo-controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: Active drug group Riociguat<br>Riociguat 0.5mg、1.0mg、2.5mg | Drug: Riociguat Oral Tablet<br>* Take any dose of Riociguat from 0.5mg to 2.5mg, or placebo<br>|
| Placebo Comparator: Placebo group<br>Placebo 0.5mg、1.0mg、2.5mg | Drug: Riociguat Oral Tablet<br>* Take any dose of Riociguat from 0.5mg to 2.5mg, or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak CI change | Change in Peak CI during the cardiopulmonary exercise test (CPET) | from baseline to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Thromboembolic Pulmonary Hypertension