A Study of Macitentan in Pulmonary Hypertension After Left Ventricular Assist Device Implantation


About this study

The purpose of this study is to evaluate the effect of macitentan 10 mg on pulmonary vascular resistance as compared to placebo in subjects with pulmonary hypertension after left ventricular assist device (LVAD) implantation


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

  • Written informed consent prior to initiation of any study-mandated procedure
  • Males or females ≥ 18 years of age
  • Surgical implantation of LVAD (e.g., HeartMate II or HeartWare) within 45 days prior to randomization
  • Hemodynamic evidence of PH on Baseline right heart catheterization.
    • Baseline RHC is defined as the last hemodynamic measurements after LVAD implantation and prior to screening. Baseline RHC can be obtained via routine RHC
    • PH is defined as: Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and Pulmonary artery wedge pressure (PAWP) ≤ 18 mmHg
  • PVR > 3 Wood units
  • Stabilization of the patient defined as
    • No LVAD pump speed/flow rate changes for 48 h prior to baseline RHC
    • Stable dose of oral diuretics for 48 h prior to baseline RHC
    • No intravenous (i.v.) inotropes or vasopressors for 48 hours (h) prior to baseline RHC
    • Patient able to ambulate 48 h prior to baseline RHC
  • A woman of childbearing potential is eligible if she has
    • A negative serum pregnancy test at screening and a negative serum pregnancy test at baseline
    • Agreed to undertake monthly serum pregnancy tests during the study and up to 30 days after study drug discontinuation
    • Agreed to use one of the methods of contraception / follow the contraception scheme described in the protocol from screening up to at least 30 days after study treatment discontinuation
  • Randomization (visit 2) must be within 14 days of baseline RHC

Exclusion Criteria

  • Documented severe obstructive lung disease defined as
    • Forced expiratory volume (FEV) in 1 second / forced vital capacity (FEV1/FVC) < 0.7 associated with FEV1 < 50% of predicted value after bronchodilator administration
  • Documented moderate to severe restrictive lung disease defined as
    • total lung capacity < 60% of predicted value
  • Documented pulmonary veno-occlusive disease
  • Patients undergoing dialysis
  • Hemoglobin < 8.5 g/dL at randomization
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) at randomization
  • Severe hepatic impairment, e.g., Child-Pugh Class C liver disease
  • Body weight < 40 kg at randomization
  • Doppler mean blood pressure < 65 mmHg at randomization
  • GFR < 30 mL/min at randomization
  • Pregnant, planning to become pregnant during the study period, or breastfeeding
  • Treatment with endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE5) inhibitors, intravenous (i.v)., subcutaneous (s.c.), or oral prostanoids, or guanylate cyclase stimulators within 7 days prior to baseline RHC, or planned treatment during the study period
  • Treatment with inhaled prostanoids (e.g., iloprost, epoprostenol) or nitric oxide within 24 h prior to baseline RHC, or planned treatment during the study period
  • Treatment with strong inducers of cytochrome P450 isozyme 3A4 (CYP3A4) within 28 days prior to study treatment initiation (e.g., carbamazepine, rifampicin, rifabutin, phenytoin and St. John's Wort)
  • Treatment with strong inhibitors of CYP3A4 within 28 days prior to study treatment initiation (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, saquinavir, boceprevir, telaprevir, iopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, and idinavir)
  • Treatment with another investigational drug within 28 days prior to study treatment initiation
  • Known hypersensitivity to ERAs, or to any of the study treatment excipients
  • Any condition that prevents compliance with the protocol or adherence to therapy
  • Known concomitant life-threatening disease with a life expectancy < 12 months

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 are currently not available

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