Clinical trial NCT06922240: Riociguat-Discontinue Effects on Right HEART in CTEPH (RED-HEART)
Official title: Effect of Discontinuation of Riociguat on Right Heart Function in Patients With CTEPH After Combination Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Thromboembolic Pulmonary Hypertension
Keywords: Chronic Thromboembolic Pulmonary Hypertension
Riociguat
Right heart function
Lead sponsor: Beijing Chao Yang Hospital
Sponsor class: OTHER
Collaborators: name: China-Japan Friendship Hospital
name: Beijing Anzhen Hospital
First posted: 2025-04-10
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Riociguat and balloon pulmonary angioplasty (BPA) are established standard-of-care interventions for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) with comparable evidence levels. However, the optimal combined treatment strategy remains unclear. Specifically, there is no consensus on whether riociguat should be continued long-term after achieving hemodynamic stability with BPA. Additionally, the long-term effects of riociguat discontinuation on right ventricular (RV) structure and function remain poorly characterized, particularly due to the lack of comprehensive noninvasive evaluations integrating cardiac magnetic resonance (CMR) and echocardiography. This prospective study aims to determine the hemodynamic impact of riociguat discontinuation in inoperable CTEPH patients who have achieved BPA treatment endpoints using right heart catheterization (RHC). Evaluate RV remodeling and functional changes after riociguat cessation through multimodal noninvasive imaging (CMR, echocardiography). Assess safety outcomes and identify potential rebound pulmonary hypertension or decompensated RV dysfunction associated with riociguat withdrawal.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years old
* CTEPH was diagnosed and one of the following three factors was met: Pulmonary endarterectomy was technically impossible; Pulmonary endarterectomy is technically feasible, but the risk-benefit ratio is poor; Residual/recurrent pulmonary hypertension after pulmonary endarterectomy
* Subjects had been treated with BPA and had received a stable dose of riociguat for ≥12 weeks
* mPAP \< 30mmHg
* Male subjects and female subjects of reproductive age are required to use effective contraception for at least 28 days after signing the informed consent form. Male subjects are not allowed to donate sperm and female subjects are not allowed to breastfeed.
* Subjects voluntarily sign written informed consent

Exclusion Criteria:

* Severe hepatic and renal insufficiency (Child-Pugh Grade C/creatinine clearance \< 30ml/min·1.73m²)
* The presence of severe infectious disease or severe bleeding tendency
* Combined with pulmonary hypertension of other types than CTEPH
* Other pulmonary hypertension targeting drugs are being used
* The expected survival time with cancer or other diseases is less than 6 months
* Pregnancy, lactation
* Subjects are currently participating in an interventional clinical trial
* In the investigator's judgment, a subject's medical abnormality, physical condition, or medical history may affect his or her ability to participate in or complete the study

Primary outcomes:
measure: Change from Baseline in the Cardiac Output at 6 Months.
timeFrame: Baseline and 6-month follow-up
Secondary outcomes:
measure: Change from Baseline in the Pulmonary Vascular Resistance at 6 Months.
timeFrame: Baseline and 6-month follow-up
measure: Change from Baseline in the concentration of NT-proBNP at 6 Months.
timeFrame: Baseline and 6-month follow-up
measure: Change from Baseline in the 6-minute walking distance at 6 Months.
timeFrame: Baseline, 3-month follow-up, and 6-month follow-up
measure: All-cause mortality
timeFrame: From the baseline to the completion follow-up,an average of 6 months
measure: Combined incidence of all-cause death, re-hospitalization or disability/incapacity events due to clinical exacerbation of pulmonary hypertension
timeFrame: From the baseline to the completion follow-up,an average of 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Beijing Anzhen Hospital
Study officials:
References: