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 (SERENADE)

Actelion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Heart Failure With Preserved Ejection Fraction

Treatments: Drug: Macitentan; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03153111

AC-055G202

2016-003653-15 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 143 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)
• Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
• Elevated NT-proBNP
• Pulmonary vascular disease or right ventricular dysfunction

Exclusion criteria

• Any prior valid measurement of LVEF < 40%. An echocardiogram is considered valid if its quality is sufficient to allow accurate assessment of LVEF and if it is reflective of the true status of the subject
• Cardiovascular co-morbidities (e.g., significant unrepaired structural valvular heart disease; acute coronary syndrome, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of Screening; uncontrolled heart rate from atrial fibrillation or atrial flutter, history of serious life-threatening or hemodynamically significant arrhythmia; history of or anticipated heart transplant or ventricular assist device implantation, etc)
• Systolic blood pressure (SBP) ≥ 180 mmHg, or diastolic blood pressure (DBP) ≥ 110 mmHg during Screening
• Hemoglobin < 100g/L (< 10 g/dl) at Screening
• Significant parenchymal lung disease (e.g., severe COPD, moderate or severe restrictive lung disease, diffuse interstitial fibrosis or alveolitis, pulmonary thromboembolism)
• Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min per 1.73 m2
• Severe hepatic impairment, e.g., Child Pugh Class C

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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143 participants in 2 patient groups, including a placebo group

Macitentan

Active Comparator group

Description:

Subjects randomized to the macitentan arm receives one tablet of macitentan 10 mg every day for at least 24 to maximum 52 weeks.

Treatment:

Drug: Macitentan

Placebo

Placebo Comparator group

Description:

Subjects randomized to the placebo arm received one tablet of placebo every day for at least 24 to maximum 52 weeks.

Treatment:

Drug: Placebo