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

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ClinicalTrials.gov Identifier: NCT02554903
Recruitment Status : Recruiting
First Posted : September 18, 2015
Last Update Posted : December 21, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: Macitentan 10mg Drug: Placebo sugar pill Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of Macitentan in Patients With Pulmonary Hypertension After Left Ventricular Assist Device Implantation
Actual Study Start Date : March 28, 2016
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Macitentan

Arm Intervention/treatment
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.
Drug: Macitentan 10mg
2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
Other Name: Active drug

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.
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
Other Name: placebo comparator




Primary Outcome Measures :
  1. Pulmonary Vascular Resistance (PVR) ratio of Week 12 to Baseline. [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Change from Baseline to Week 12 in mean right atrial pressure (mPAP) [ Time Frame: 12 weeks ]
  2. Change from Baseline to Week 12 in mean pulmonary arterial pressure (mPAP) [ Time Frame: 12 weeks ]
  3. Change from Baseline to Week 12 in pulmonary arterial wedge pressure (PAWP) [ Time Frame: 12 weeks ]
  4. Change from Baseline to Week 12 in cardiac index (CI) [ Time Frame: 12 weeks ]
  5. Change from Baseline to Week 12 in total pulmonary resistance [ Time Frame: 12 weeks ]
  6. Change from Baseline to Week 12 in mixed venous oxygen saturation [ Time Frame: 12 weeks ]
  7. Change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from Baseline to Week 12. [ Time Frame: 12 weeks ]
  8. Change in World Health Organization (WHO) functional class from Baseline to Week 12 [ Time Frame: 12 weeks ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02554903


Contacts
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Contact: Mona Selej, MD 650-624-6900 mselej@its.jnj.com
Contact: Peter Agron, PhD 650-624-6900 pagron@its.jnj.com

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Locations
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United States, Arizona
#125_Mayo Clinic Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Robert Scott, MD         
#144_University of Arizona Recruiting
Tucson, Arizona, United States, 85724
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jennifer Cook, MD         
United States, California
#106_Cedars-Sinai Medical Center Recruiting
Beverly Hills, California, United States, 90211
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jaime Moriguchi, MD         
#154_University of California San Diego Recruiting
La Jolla, California, United States, 92037
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Eric Adler, MD         
#110_Sutter Heart Institute Recruiting
Sacramento, California, United States, 95819
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: John Chin, MD         
#132_University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Munir Janmohamed, MD         
United States, District of Columbia
#123_MedStar Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: David Majure, MD         
United States, Florida
#126_Florida Hospital Recruiting
Orlando, Florida, United States, 32804
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Scott Silvestry, MD         
United States, Illinois
#135_University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Valluvan Jeevanandam, MD         
#113_Advocate Christ Medical Center Recruiting
Oak Lawn, Illinois, United States, 60453
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Antone Tatooles, MD         
United States, Indiana
#108_Indiana University Health Physicians Cardiology Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Marco Caccamo, DO         
#112_St. Vincent Medical Group, Inc Recruiting
Indianapolis, Indiana, United States, 46260
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Ashwin Ravichandran, MD         
United States, Iowa
#120_University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Vladimir Cotarlan-Nistor, MD         
United States, Kentucky
#152_University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Maya Guglin, MD         
#117_University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Emma Birks, MD         
United States, Louisiana
#105_Ochsner Medical Center Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Stacy Mandra, MD         
United States, Maryland
#129_John Hopkins University Medical Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Ryan Tedford, MD         
United States, Massachusetts
#143_Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Amanda Vest, MD         
#138_Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Greg Lewis, MD         
#119_Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Michael Givertz, MD         
United States, Michigan
#115_Henry Ford Hospital Withdrawn
Detroit, Michigan, United States, 48202
United States, Minnesota
#102_Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: US Med Info US Med Info       usmedinfo@actelion.com   
Principal Investigator: Robert Frantz, MD         
United States, Missouri
#150_Saint Luke's Hospital Recruiting
Kansas City, Missouri, United States, 64111
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Mark Everley, MD         
#104_Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Shane LaRue, MD         
United States, Nebraska
#131_University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68918
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Ronald Zolty, MD         
United States, New York
#133_Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Ulrich Jorde, MD         
#103_Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Evelyn Horn, MD         
#139_Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 94080
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Raymond Bietry, MD         
#147_Westchester Medical Center Recruiting
Valhalla, New York, United States, 10595
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Gregg Lanier, MD         
United States, Ohio
#148_University of Cincinnati Medical Center Recruiting
Cincinnati, Ohio, United States, 45242
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jean Elwing, MD         
#153_Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Miriam Jacob, MD         
#101_The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Veronica Franco, MD         
#145_The University of Toledo Medical Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Mark Bonnell         
United States, Oklahoma
#121_Integris Baptist Medical Center Recruiting
Oklahoma City, Oklahoma, United States, 73112
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Doug Horstmanshof, MD         
United States, Pennsylvania
#142_Penn State Heart and Vascular Institute Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: David Silber, MD         
#140_Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jeremy Mazurek, MD         
#134_Allegheny General Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Richard Agarwal, MD         
#130_University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jeffery Teuteberg, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Brian Houston         
#141_Palmetto Health / Palmetto Heart Recruiting
Columbia, South Carolina, United States, 29203
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Patrick J McCann, MD         
United States, Tennessee
#151_Stern Cardiovascular Foundation Recruiting
Memphis, Tennessee, United States, 38120
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jawwad Yusuf, MD         
#146_Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Mary Keebler, MD         
United States, Texas
#149_Seton Heart Institute Recruiting
Austin, Texas, United States, 78705
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Ernest Haeusslein, MD         
#136_Baylor Health - Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75226
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Shelley Hall, MD         
#107_Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Myung Park, MD         
#122_Advanced Heart Failure Clinic - HCM Recruiting
San Antonio, Texas, United States, 78229
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Chandra Kunavarapu, VM         
United States, Utah
#127_The University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Edward Gilbert, MD         
United States, Virginia
#114_University of Virginia Recruiting
Charlottesville, Virginia, United States, 22905
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Jamie Kennedy, MD         
#111_Inova Fairfax Hospital Recruiting
Falls Church, Virginia, United States, 22042
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Shashank Desai, MD         
#116_Virginia Commonwealth University (VCU) Medical Center Recruiting
Richmond, Virginia, United States, 23298
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Melissa Smallfield, MD         
United States, Wisconsin
#155_University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Med Info       usmedinfo@actelion.com   
Principal Investigator: Ravi Dhingra         
Sponsors and Collaborators
Actelion

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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT02554903     History of Changes
Other Study ID Numbers: AC-055-205
First Posted: September 18, 2015    Key Record Dates
Last Update Posted: December 21, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Actelion:
LVAD

Additional relevant MeSH terms:
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Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Macitentan
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists