A Study to Evaluate Whether Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

Overview

About this study

This is a study to evaluate whether macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary vascular disease. The primary objective is to evaluate whether macitentan 10 mg reduces N-terminal pro-brain natriuretic peptide (NT-pro-BNP) as compared to placebo in these patients.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Signed informed consent prior to any study-mandated procedure 
  • Signs or symptoms of Heart Failure (HF) (NYHA FC I I and II I ) requiring treatment with at least one oral diuretic (any type)
  • Left ventricular ejection fraction (LVEF) ≥ 40% (by echocardiography at Screening)
  • New York Heart Association (NYHA) functional class (FC) II to III 
  • Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
  • Patients with HFpEF defined as either one of the following by echocardiography at Screening:
    • a. Left atrial (LA) enlargement:
      • Left atrial volume > 58 mL (male) / > 52 mL (female) or
      • Left atrial volume index ≥ 28 mL/m2, or 
      • LA area > 20 cm2, or
      • LA diameter > 4.0 cm (male) / > 3.8 cm (female)
    • Left ventricular septal thickness or posterior wall thickness ≥ 1.1 cm 8. Elevated NT-proBNP / BNP ≥ 200 / 60 pg/mL for subjects in sinus rhythm or ≥ 500 / 150 pg/mL for subjects with atrial fibrillation (AF) at any time within 3 months prior to Screening or at Screening
  • Elevated NT-proBNP / BNP ≥ 200 / 60 pg/mL for subjects in sinus rhythm or ≥ 500 / 150 pg/mL for subjects with atrial fibrillation (AF) at any time within 3 months prior to Screening or at Screening 
  • Pulmonary vascular disease or right ventricular (RV) dysfunction meeting at least one of the following echocardiographic (at Screening) and/or right heart catheterization (RHC) parameters (at Screening or from any RHC previously performed): 
    • Echocardiographic peak TR velocity > 2.8 m/s or invasive mean pulmonary artery pressure ≥ 25 mmHg (RHC) or PASP > 40 mmHg and evidence of RV dysfunction (TAPSE < 17 mm or RV fractional area change < 35% or RV tissue Doppler s’ velocity < 9.5 cm/s)
    • Diastolic Pulmonary Vascular Pressure Gradient (DPG) > 5 mmHg (RHC) 
    • Pulmonary vascular resistance (PVR) > 3 Wood Units (RHC)
  • A woman of childbearing potential must have a negative pre-treatment serum pregnancy test, agree to use reliable contraception from at least 30 days prior to Visit 2 up to at least 30 days after study treatment discontinuation, and agree to undertake monthly pregnancy tests from Screening up to at least 30 days after study treatment discontinuation.

Exclusion Criteria:

  • Any prior measurement of LVEF < 40%.
  • Significant unrepaired structural valvular heart disease (i.e., greater than mild aortic or mitral stenosis, and greater than moderate aortic or mitral regurgitation)
  • Hypertrophic, restrictive, and infiltrative cardiomyopathies
  • Pericardial disease
  • Acute coronary syndrome, including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable coronary artery disease or has undergone coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of screening.
  • Known indication for PCI or CABG
  • Uncontrolled heart rate (HR) from atrial fibrillation or atrial flutter (> 110 beats per minute) as assessed by ECG
  • History of serious life-threatening or hemodynamically significant arrhythmias, including symptomatic or sustained ventricular tachycardia or defibrillator shock within 12 month(s) of Screening
  • History of or anticipated heart transplant or anticipated/implanted ventricular assist device
  • Transient ischemic attack (TIA) or stroke within 3 months of Screening
  • Systolic blood pressure (SBP) ≥ 180 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Robert Scott, M.D., Ph.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Additional contact information

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