THERAPY-HYBRID-BPA trial

JRCT ID: jRCTs041200052

Registered date:22/10/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: chronic thromboembolic pulmonary hypertension
• Date of first enrollment: 22/10/2020
• Target sample size: 72
• Study type: Interventional
• Intervention(s): In this study, we will perform continuous verification by allocating the Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients whose hemodynamics were normalized after Balloon Pulmonary Angioplasty (BPA) to the the riociguat active group and placebo group for 16 weeks.

Outcome(s)

• Primary Outcome: Change in Peak CI during cardiopulmonary exercise test (CPET) from baseline to 16 weeks

Secondary Outcome

1. Change in hemodynamic index during CPET from baseline to 16 weeks (Peak, 20W).
Cardiac output (CO), Pulmonary artery pressure (PAP), Pulmonary artery wedge pressure (PAWP), Right atrial pressure (RAP) Pulmonary vascular resistance (PVR), Total pulmonary resistance (TPR), Heart Rate (HR), Stroke volume (SV), Mixed venous oxygen saturation (SvO2), Percutaneous oxygen saturation (SpO2), Arterial oxygen saturation (SaO2), Arterial oxygen partial pressure (PaO2), PA compliance, Anaerobic threshold (AT), Mean PAP/CO slope, Peak VO2, Non-invasive blood pressure (NIBP), Arterial Blood Pressure (ABP), VE/VCO2, VE/VCO2 slope, End-tidal carbon dioxide partial pressure (PETCO2), Ratio of dead space to tidal volume (Vd/Vt)
2. Change in hemodynamic index at rest from baseline to 16 weeks.
(PAP, PAWP, CO, CI, RAP, PVR, TPR, HR, SV, SvO2, SpO2, PA compliance, NIBP)
3. Change in WHO functional classification from baseline to 16 weeks.
4. Change in 6-minute walking distance and modified Borg scale from baseline to 16 weeks.
5. Change in BNP value from baseline to 16 weeks.
6. Adverse events (AE)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 85age old
• Gender: Both

Include criteria

(1)Patients who meet CTEPH diagnostic criteria (complying with 2017 Japanese Cardiovascular Society Guidelines diagnostic criteria)
(2)Diagnosed as a contraindication of pulmonary endarterectomy by centraldiagnosis
(3)Patients who were adjusted to reach the appropriate dose of riociguat within 8weeks and were able to continueoral administration thereafter
(4)Patients who received BPA once or more after the dose adjustment of riociguat
(5)Patients who have been able to continue taking the same dose for more than 3months
(6)Patients who can obtain written informed consent from the patients and legal representatives
(7)Patients with WHO functional class II or III at the time of allocation
(8)Over the age of 18 and under 85 at the time of obtaining consent
(9)Patients with a resting CI value of less than 5.0 L/min/m2 in theright heart catheterization test immediatelybefore allocation
(10)Patients with a mean pulmonary artery pressure less than 25 mmHg in a rightheart catheterization test immediately before allocation

Exclude criteria

(1) Patients who are eligible for pulmonary endarterectomy (PEA)
(2) Patients With pulmonary hypertension other than class 4 by NICE classification
(3) Patients having difficulty in performing cardiopulmonary exercise test (CPET)
(4) Patients with severe right heart failure requiring cardiotonic drugs
(5) Patients with severe heart disease
(6) Patients with severe liver damage
(7) Patients with systolic blood pressure less than 90 mmHg at screening
(8) Patients with shunt disease
(9) (Contraindications) Patients with severe renal dysfunction (CCr <15 mL/min) or on dialysis
(10) Patients with life expectancy less than 2 years
(11) Being pregnant or lactating
(12) Patients who are contraindicated for riociguat
(13) Using other unlicensed drugs
(14) Patients who used a pulmonary vasodilator within 4 weeks after the consent of the right heart catheter test.
(15) Investigator determines that whose participation in this study is not appropriate

Related Information

• Primary Sponsor: Shimokawahara Hiroto
• Source(s) of Monetary Support: Bayer Yakuhin, Ltd.