Clinical Study to Assess the Efficacy and Safety of Macitentan in Patients With Pulmonary Hypertension After Left Ventricular Assist Device Implantation

Study Purpose

STUDY OBJECTIVES Primary objective To evaluate the effect of macitentan 10 mg on pulmonary vascular resistance (PVR) as compared to placebo in subjects with pulmonary hypertension (PH) after left ventricular assist device (LVAD) implantation. Secondary objectives To evaluate the effect of macitentan 10 mg as compared to placebo on cardio-pulmonary hemodynamics and disease severity in subjects with PH after LVAD implantation. To evaluate the safety and tolerability of macitentan 10 mg in subjects with PH after LVAD implantation. Exploratory objectives To explore the potential effect of macitentan 10 mg as compared to placebo on right ventricular function in subjects with PH after LVAD implantation. To explore the potential effect of macitentan 10 mg as compared to placebo on selected clinical events in subjects with PH after LVAD implantation. To explore the potential effect of macitentan 10 mg as compared to placebo on renal function as measured by glomerular filtration rate (GFR) in subjects with PH after LVAD implantation.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Written Informed Consent prior to initiation of any study-mandated procedure. 2. Males or females ≥ 18 years of age. 3. Surgical implantation of LVAD within 90 days prior to Randomization. 4. Hemodynamic evidence of PH on Baseline right heart catheterization (RHC) by the thermodilution method. Baseline RHC is defined as the last hemodynamic measurements after LVAD implantation and prior to the first dose of study treatment. PH is defined as: 1. Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and 2. Pulmonary artery wedge pressure (PAWP) ≤ 18 mmHg and 3. PVR > 3 Wood units. 5. Stabilization of the patient for 48 h prior to the Baseline RHC, defined as: 1. No LVAD pump speed/flow rate changes and 2. Stable dose of oral diuretics and 3. No intravenous (i.v.) inotropes or vasopressors and 4. Patient able to ambulate. 6. A woman of childbearing potential is eligible only if she has: 1. A negative serum pregnancy test result during the Screening period (Visit 1) and Randomization (Visit 2) and 2. Agreement to undertake monthly serum pregnancy tests during the study and up to 30 days after study treatment discontinuation and 3. Agreement to use one of the methods of contraception / follow the contraception scheme described in Section 4.5 from Screening and up to at least 30 days after study treatment discontinuation. 7. Patient must be randomized within 14 days of Baseline RHC.

Exclusion Criteria:

1. Documented severe obstructive lung disease defined as: forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) < 0.7 associated with FEV1 < 50% of predicted value after bronchodilator administration. 2. Documented moderate to severe restrictive lung disease defined as: total lung capacity < 60% of predicted value. 3. Documented pulmonary veno-occlusive disease. 4. Patients undergoing dialysis. 5. Hemoglobin < 8.5 g/dL at Randomization. 6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) at Randomization. 7. Severe hepatic impairment, e.g., Child-Pugh Class C liver disease. 8. Body weight < 40 kg at Randomization. 9. Doppler mean blood pressure < 65 mmHg at Randomization. 10. GFR < 30 mL/min at Randomization. 11. Pregnant, planning to become pregnant during the study period, or breastfeeding. 12. Treatment with endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE5) inhibitors, i.v., subcutaneous (s.c.), or oral prostanoids, or guanylate cyclase stimulators within 7 days prior to Baseline RHC or study treatment initiation. 13. Treatment with inhaled prostanoids (e.g., iloprost, epoprostenol) or nitric oxide within 24 h prior to Baseline RHC or study treatment initiation. 14. 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). 15. 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). 16. Treatment with another investigational drug (planned, or taken) within 28 days prior to study treatment initiation. 17. Known hypersensitivity to ERAs, or to any of the study treatment excipients. 18. Any condition that prevents compliance with the protocol or adherence to therapy. 19. Known concomitant life-threatening disease with a life expectancy < 12 months.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02554903
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Actelion
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Mark Rocco
Principal Investigator Affiliation Actelion
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Active, not recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary Hypertension
Arms & Interventions

Arms

Experimental: Macitentan 10 mg po

Approximately 78 adult subjects with PH post-LVAD implantation will be randomized (1:1) to receive either macitentan 10 mg, or matching placebo, once daily orally.

Placebo Comparator: Placebo sugar pill

Approximately 78 adult subjects with PH post-LVAD implantation will be randomized (1:1) to receive either macitentan 10 mg, or matching placebo, once daily orally.

Interventions

Drug: - Macitentan 10mg

2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo

Drug: - Placebo sugar pill

2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

#125_Mayo Clinic Arizona, Phoenix, Arizona

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Address

#125_Mayo Clinic Arizona

Phoenix, Arizona, 85054

#144_University of Arizona, Tucson, Arizona

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#144_University of Arizona

Tucson, Arizona, 85724

#106_Cedars-Sinai Medical Center, Beverly Hills, California

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#106_Cedars-Sinai Medical Center

Beverly Hills, California, 90211

#154_University of California San Diego, La Jolla, California

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#154_University of California San Diego

La Jolla, California, 92037

#110_Sutter Heart Institute, Sacramento, California

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#110_Sutter Heart Institute

Sacramento, California, 95819

San Francisco, California

Status

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#132_University of California San Francisco

San Francisco, California, 94143

#123_MedStar Washington Hospital Center, Washington, District of Columbia

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#123_MedStar Washington Hospital Center

Washington, District of Columbia, 20010

#126_Florida Hospital, Orlando, Florida

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#126_Florida Hospital

Orlando, Florida, 32804

Chicago, Illinois

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#135_University of Chicago Medical Center

Chicago, Illinois, 60637

#113_Advocate Christ Medical Center, Oak Lawn, Illinois

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#113_Advocate Christ Medical Center

Oak Lawn, Illinois, 60453

Indianapolis, Indiana

Status

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#108_Indiana University Health Physicians Cardiology

Indianapolis, Indiana, 46202

#112_St. Vincent Medical Group, Inc, Indianapolis, Indiana

Status

Address

#112_St. Vincent Medical Group, Inc

Indianapolis, Indiana, 46260

Iowa City, Iowa

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#120_University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

#117_University of Louisville, Louisville, Kentucky

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#117_University of Louisville

Louisville, Kentucky, 40202

#105_Ochsner Medical Center, New Orleans, Louisiana

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#105_Ochsner Medical Center

New Orleans, Louisiana, 70121

Baltimore, Maryland

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#129_John Hopkins University Medical Center

Baltimore, Maryland, 21287

#143_Tufts Medical Center, Boston, Massachusetts

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#143_Tufts Medical Center

Boston, Massachusetts, 02111

#138_Massachusetts General Hospital, Boston, Massachusetts

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Address

#138_Massachusetts General Hospital

Boston, Massachusetts, 02114

#119_Brigham and Women's Hospital, Boston, Massachusetts

Status

Address

#119_Brigham and Women's Hospital

Boston, Massachusetts, 02115

#115_Henry Ford Hospital, Detroit, Michigan

Status

Address

#115_Henry Ford Hospital

Detroit, Michigan, 48202

#102_Mayo Clinic, Rochester, Minnesota

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Address

#102_Mayo Clinic

Rochester, Minnesota, 55905

#150_Saint Luke's Hospital, Kansas City, Missouri

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#150_Saint Luke's Hospital

Kansas City, Missouri, 64111

Saint Louis, Missouri

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Address

#104_Washington University School of Medicine

Saint Louis, Missouri, 63110

Omaha, Nebraska

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#131_University of Nebraska Medical Center

Omaha, Nebraska, 68918

#133_Montefiore Medical Center, Bronx, New York

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Address

#133_Montefiore Medical Center

Bronx, New York, 10467

#103_Weill Cornell Medical College, New York, New York

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#103_Weill Cornell Medical College

New York, New York, 10021

New York, New York

Status

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#139_Icahn School of Medicine at Mount Sinai

New York, New York, 94080

#147_Westchester Medical Center, Valhalla, New York

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#147_Westchester Medical Center

Valhalla, New York, 10595

Cincinnati, Ohio

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#148_University of Cincinnati Medical Center

Cincinnati, Ohio, 45242

#153_Cleveland Clinic, Cleveland, Ohio

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#153_Cleveland Clinic

Cleveland, Ohio, 44195

Columbus, Ohio

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Address

#101_The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210

Toledo, Ohio

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Address

#145_The University of Toledo Medical Center

Toledo, Ohio, 43614

#121_Integris Baptist Medical Center, Oklahoma City, Oklahoma

Status

Address

#121_Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112

Hershey, Pennsylvania

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#142_Penn State Heart and Vascular Institute

Hershey, Pennsylvania, 17033

Philadelphia, Pennsylvania

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#140_Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

#134_Allegheny General Hospital, Pittsburgh, Pennsylvania

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#134_Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212

Pittsburgh, Pennsylvania

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#130_University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213

Medical University of South Carolina, Charleston, South Carolina

Status

Address

Medical University of South Carolina

Charleston, South Carolina, 29425

#141_Palmetto Health / Palmetto Heart, Columbia, South Carolina

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Address

#141_Palmetto Health / Palmetto Heart

Columbia, South Carolina, 29203

#151_Stern Cardiovascular Foundation, Memphis, Tennessee

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#151_Stern Cardiovascular Foundation

Memphis, Tennessee, 38120

Nashville, Tennessee

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Address

#146_Vanderbilt University Medical Center

Nashville, Tennessee, 37232

#149_Seton Heart Institute, Austin, Texas

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#149_Seton Heart Institute

Austin, Texas, 78705

Dallas, Texas

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#136_Baylor Health - Baylor University Medical Center

Dallas, Texas, 75226

#107_Houston Methodist Hospital, Houston, Texas

Status

Address

#107_Houston Methodist Hospital

Houston, Texas, 77030

#122_Advanced Heart Failure Clinic - HCM, San Antonio, Texas

Status

Address

#122_Advanced Heart Failure Clinic - HCM

San Antonio, Texas, 78229

#127_The University of Utah, Salt Lake City, Utah

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Address

#127_The University of Utah

Salt Lake City, Utah, 84112

#114_University of Virginia, Charlottesville, Virginia

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Address

#114_University of Virginia

Charlottesville, Virginia, 22905

#111_Inova Fairfax Hospital, Falls Church, Virginia

Status

Address

#111_Inova Fairfax Hospital

Falls Church, Virginia, 22042

Richmond, Virginia

Status

Address

#116_Virginia Commonwealth University (VCU) Medical Center

Richmond, Virginia, 23298

Madison, Wisconsin

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#155_University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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