Clinical Trial to Evaluate the Efficacy and Safety in Concomitant Administration of Macitentan and Dapagliflozin in Patients With Heart Failure With Mildly Reduced and Preserved Ejection Fraction (HFmrEF and HFpEF) and Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH)

NCT07147114 | Not Yet Recruiting Phase 4

• 1 other identifier: MD-CpcPH
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 15

Brief Summary

This clinical trial will evaluate whether combination therapy with Dapagliflozin + Macitentan improves outcomes compared to Dapagliflozin + placebo in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH). The study will measure changes in pulmonary vascular resistance, NT-proBNP, 6-minute walk distance, and quality of life (KCCQ scores) over 24 weeks. Participants will be randomly assigned to one of two groups, take study medication for 24 weeks, and undergo regular clinical, laboratory, and safety assessments.

Conditions

Combined Pre- and Post-capillary Pulmonary Hypertension; CpcPH; HFmrEF; HFpEF; Group 2 Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Hierarchical outcome component(Change in PVR, Change in NT-proBNP, Change in 6MWD, Change in KCCQ-CSS)

  The hierarchical composite variable includes the rate of change in Pulmonary Vascular Resistance (PVR), NT-proBNP, change in 6-minute walk distance, and change in KCCQ-CSS score. All possible pairwise comparisons between combination therapy group and monotherapy group subjects (e.g., 2 subjects in combination group and 3 in monotherapy group yield 6 pairs) are classified as Win, Loss, or Tie based on the following definitions. If the subject in the pair meeting the criteria belongs to the combination group, it is evaluated as a Win; if in the monotherapy group, a Loss.

  Baseline, 24 week

Secondary Outcomes (20)

• Change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 24

  Baseline, 24 week

• Change in Mean Pulmonary Arterial Pressure (mPAP) from Baseline to Week 24

  Baseline, 24 week

• Change in Pulmonary Arterial Wedge Pressure (PAWP) from Baseline to Week 24

  Baseline, 24 week

• Change in 6-Minute Walk Distance from Baseline to Week 24

  Baseline, 24 week

• Change in Oxygen Saturation (SpO2) Difference Before and After 6-Minute Walk Test from Baseline to Week 24

  Baseline, 24 week

Study Arms (2)

Combination therapy group

EXPERIMENTAL

Maciten Tab. 10mg

Drug: Combination therapy

Monotherapy group

PLACEBO COMPARATOR

Dapozin Tab. 10mg or 5mg

Drug: Monotherapy

Interventions

Combination therapy DRUG

Macitentan 10mg, Dapagliflozin 10mg or 5mg po tablet q.d. in 24 weeks

Also known as: Maciten Tab. 10mg

Combination therapy group

Monotherapy DRUG

Macitentan placebo, Dapagliflozin 10mg or 5mg po tablet q.d. in 24 weeks

Also known as: Dapozin Tab. 10mg or 5mg

Monotherapy group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \<Screening Visit (Visit 1)\>
• A male or female adults aged 19 years or older in South Korea
• LVEF greater than 40% on echocardiogram performed within 12 weeks prior to screening
• Presence of heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) accompanied by combined pre- and post-capillary pulmonary hypertension (CpcPH)
• Meeting all of the following criteria on RHC performed within 48 weeks prior to screening:
• mPAP \> 20 mmHg
• PVR \> 2 Wood units (WU)
• PAWP \> 15 mmHg
• World Health Organization Functional Class (WHO-FC) II or III at the time of screening
• If taking any of the following medications at the time of screening, the participant must have been on a stable dose for at least 3 months:
• Renin-angiotensin system inhibitors
• Beta-blockers
• Mineralocorticoid receptor antagonists (aldosterone antagonists)
• Sodium-glucose cotransporter-2 (SGLT2) inhibitors
• Ivabradine

You may not qualify if:

• \<Screening Visit (Visit 1)\>
• Known hypersensitivity to the active ingredients (Macitentan, Dapagliflozin) or any excipients of the investigational medicinal product
• Pregnant or breastfeeding women, or those who do not agree to use at least two appropriate contraceptive methods\* (self or partner) during the clinical trial period and for 30 days after the last administration of the investigational medicinal product (for male participants, those who do not agree to refrain from sperm donation)
• \*: a. Surgical sterilization (e.g., vasectomy) or intrauterine device (IUD; copper IUD or hormone-releasing intrauterine system), b. Non-oral hormonal contraceptive or spermicide in combination with a barrier method, c. Cervical cap or diaphragm used in combination with a male condom.
• Participants with type 1 diabetes mellitus or secondary diabetes mellitus
• Participants with metabolic acidosis, such as diabetic ketoacidosis
• Participants diagnosed with pulmonary hypertension other than WHO Group 2 pulmonary hypertension (i.e., WHO Group 1, 3, 4, or 5)
• Group 1: Pulmonary arterial hypertension
• Group 3: Pulmonary hypertension associated with lung diseases and/or hypoxia
• Group 4: Chronic thrombo-embolic pulmonary hypertension
• Group 5: Pulmonary hypertension with unclear and/or multifactorial mechanisms
• Participants who meet the following criteria on RHC performed within 48 weeks prior to screening:
• a. PAWP ≤ 15 mmHg
• History of taking any of the following medications within 4 weeks prior to screening:
• Calcium channel blockers

Sponsors & Collaborators

• Gachon University Gil Medical Center: lead

Study Sites (15)

Pusan National University Hospital

Busan, 49241, South Korea

Location

Chungbuk National University Hospital

Chungju, 28644, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

Incheon Sejong Hospital

Incheon, 21080, South Korea

Location

Gachon University Gil Hospital

Incheon, 405-760, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Yonsei University Health System, Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St.Mary

Seoul, 06591, South Korea

Location

Koera University Guro Hospital

Seoul, 08308, South Korea

Location

Yonsei University, Wonju Severance Christian Hospital

Wŏnju, 26426, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

MeSH Terms

Interventions

Combined Modality Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Wook-Jin Chung, MD, PhD

CONTACT

82-32-460-3663; heart@gilhospital.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 21, 2025
• First Posted: August 28, 2025
• Study Start: October 31, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (15)