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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 15-008912
    NCT ID: NCT02554903
    Sponsor Protocol Number: AC-055-205

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. If you need assistance understanding the eligibility criteria, please contact the study team.

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 us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

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

Open for enrollment

Contact information:

Leena Abraham R.N.

(480)342-6750

Abraham.Leena@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20190920

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