Riociguat-Discontinue Effects on Right HEART in CTEPH (RED-HEART) (RED-HEART)

Effect of Discontinuation of Riociguat on Right Heart Function in Patients With CTEPH After Combination Therapy

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Drug: Riociguat; Drug: Routine Treatment

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Suqiao Yang; Phone Number: 010-85231217; Email: yangsuqiao@126.com

Study Locations

• China
  • Beijing, China, 100029
    • Recruiting
    • China-Japan Friendship Hospital
    • Contact: Shuai Zhang, Dr.; Phone Number: ＋8618501259164; Email: shuaizhang2012@126.com
    • Principal Investigator: Wanmu Xie, Professor
  • Beijing, China, 100020
    • Recruiting
    • Beijing Chao-Yang Hospital
    • Contact: Guangxu Liu, Dr.; Phone Number: +861085231129; Email: bjcyh_yjxbf@163.com
    • Principal Investigator: Suqiao Yang, Professor
  • Beijing, China, 101118
    • Recruiting
    • Beijing Anzhen Hospital
    • Contact: Meng Zhang, Dr.; Phone Number: +8613552325192; Email: mmzhang0423@163.com
    • Principal Investigator: Jun Wan, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: riociguat group; The subject was given comprehensive treatment in accordance with the guidelines and oral riociguat.	Drug: Riociguat; On the basis of the comprehensive treatment in line with the guidelines, including conventional diuresis, anticoagulation, oxygen inhalation, etc., continue oral administration of riociguat for treatment.
Experimental: routine treatment group; The subject was given comprehensive treatment in accordance with the guidelines.	Drug: Routine Treatment; On the basis of the comprehensive treatment in line with the guidelines, including conventional diuresis, anticoagulation, oxygen inhalation, etc, and stop taking riociguat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Cardiac Output at 6 Months.	Cardiac Output was measured by right heart catheterization.	Baseline and 6-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Pulmonary Vascular Resistance at 6 Months.	Pulmonary Vascular Resistance was measured by right heart catheterization.	Baseline and 6-month follow-up
Change from Baseline in the concentration of NT-proBNP at 6 Months.	The concentration of NTproBNP in serum was detected in pg/ml	Baseline and 6-month follow-up
Change from Baseline in the 6-minute walking distance at 6 Months.	6-minute walking distance was measured by 6-minute walking test	Baseline, 3-month follow-up, and 6-month follow-up
All-cause mortality	Observe and record All-cause mortality	From the baseline to the completion follow-up,an average of 6 months
Combined incidence of all-cause death, re-hospitalization or disability/incapacity events due to clinical exacerbation of pulmonary hypertension	Observe and record All-cause mortality, clinical exacerbation of pulmonary hypertension leading to re-hospitalization or disability/incapacity	From the baseline to the completion follow-up,an average of 6 months

Collaborators and Investigators

• Sponsor: Suqiao Yang
• Collaborators: Beijing Anzhen Hospital; China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: March 23, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 27, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Right heart function; Chronic Thromboembolic Pulmonary Hypertension; Riociguat
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Enzyme Activators; Riociguat
• Other Study ID Numbers: BRWEP2024W112030108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No