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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
64
Macitentan 10mg, Dapagliflozin 10mg or 5mg po tablet q.d. in 24 weeks
Macitentan placebo, Dapagliflozin 10mg or 5mg po tablet q.d. in 24 weeks
Pusan National University Hospital
Busan, South Korea
Chungbuk National University Hospital
Chungju, South Korea
Keimyung University Dongsan Hospital
Daegu, South Korea
Chungnam National University Hospital
Daejeon, South Korea
Chonnam National University Hospital
Gwangju, South Korea
Incheon Sejong Hospital
Incheon, South Korea
Gachon University Gil Hospital
Incheon, South Korea
Seoul National University Hospital
Seoul, South Korea
Yonsei University Health System, Severance Hospital
Seoul, South Korea
Asan Medical Center
Seoul, South Korea
...and 5 more locations
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.
Time frame: Baseline, 24 week
Change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 24
PVR (Wood Units, WU) is measured by Right Heart Catheterization (RHC).
Time frame: Baseline, 24 week
Change in Mean Pulmonary Arterial Pressure (mPAP) from Baseline to Week 24
mPAP (mmHg) is measured by RHC.
Time frame: Baseline, 24 week
Change in Pulmonary Arterial Wedge Pressure (PAWP) from Baseline to Week 24
PAWP (mmHg) is measured by RHC.
Time frame: Baseline, 24 week
Change in 6-Minute Walk Distance from Baseline to Week 24
Distance (meters) measured by 6-minute walk test.
Time frame: Baseline, 24 week
Change in Oxygen Saturation (SpO2) Difference Before and After 6-Minute Walk Test from Baseline to Week 24
Oxygen saturation (%) difference before and after the 6-minute walk test.
Time frame: Baseline, 24 week
Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from Baseline to Week 24
NT-proBNP (pg/mL) measured by clinical laboratory tests.
Time frame: Baseline, 24 week
Change in Tricuspid Regurgitation Velocity (TRV) from Baseline to Week 24
TRV (m/s) measured by echocardiography.
Time frame: Baseline, 24 week
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) from Baseline to Week 24
TAPSE (mm) measured by echocardiography.
Time frame: Baseline, 24 week
Use of Intravenous Diuretics During Treatment Period (Visit 2 to Visit 4)
The number of intravenous diuretic administrations collected via concomitant medication records.
Time frame: Baseline, 24 week
Rate of Hospitalization Due to Heart Failure During Treatment Period (Visit 2 to Visit 4)
Number of hospitalizations for heart failure compared between groups during treatment period.
Time frame: Baseline, 24 week
Number of Days Hospitalized for Heart Failure During Treatment Period (Visit 2 to Visit 4)
Total days of hospitalization for heart failure compared between groups during treatment.
Time frame: Baseline, 24 week
Number of Deaths (Cardiovascular and All-Cause) During Treatment Period (Visit 2 to Visit 4)
Cardiovascular and all-cause mortality events compared between groups.
Time frame: Baseline, 24 week
Change in Mean Right Atrial Pressure (mRAP) from Baseline to Week 24
mRAP (mmHg) measured by RHC.
Time frame: Baseline, 24 week
Change in Cardiac Index (CI) from Baseline to Week 24
Cardiac Index (L/min/m²) measured by RHC.
Time frame: Baseline, 24 week
Change in Mixed Venous Oxygen Saturation (SvO2) from Baseline to Week 24
SvO2 (%) measured by RHC.
Time frame: Baseline, 24 week
Change in Left Atrial Volume Index (LAVI) from Baseline to Week 24
LAVI (mL/m²) measured by echocardiography and body measurements.
Time frame: Baseline, 24 week
Change in Tricuspid Valve Systolic Tissue Velocity (TV S' velocity) from Baseline to Week 24
TV S' velocity (cm/s) measured by echocardiography.
Time frame: Baseline, 24 week
Change in Right Atrial Area (RA area) from Baseline to Week 24
RA area (cm²) measured by echocardiography.
Time frame: Baseline, 24 week
Change in Presence of Pericardial Effusion from Baseline to Week 24
Presence or absence of pericardial effusion evaluated by echocardiography.
Time frame: Baseline, 24 week
Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) from Baseline to Week 24
KCCQ-OSS measured by questionnaire.
Time frame: Baseline, 24 week
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