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

NCT ID: NCT02554903

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-28
• Study Completion Date: 2020-03-13

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.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Macitentan 10mg

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo sugar pill

Intervention Type: DRUG

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

Interventions

Macitentan 10mg

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Active drug; placebo comparator

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Rocco

Role: STUDY_DIRECTOR

Actelion

Locations

#125_Mayo Clinic Arizona

Phoenix, Arizona, United States

#144_University of Arizona

Tucson, Arizona, United States

#106_Cedars-Sinai Medical Center

Beverly Hills, California, United States

#154_University of California San Diego

La Jolla, California, United States

#110_Sutter Heart Institute

Sacramento, California, United States

#132_University of California San Francisco

San Francisco, California, United States

#123_MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

#126_Florida Hospital

Orlando, Florida, United States

#135_University of Chicago Medical Center

Chicago, Illinois, United States

#113_Advocate Christ Medical Center

Oak Lawn, Illinois, United States

#108_Indiana University Health Physicians Cardiology

Indianapolis, Indiana, United States

#112_St. Vincent Medical Group, Inc

Indianapolis, Indiana, United States

#120_University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

#117_University of Louisville

Louisville, Kentucky, United States

#105_Ochsner Medical Center

New Orleans, Louisiana, United States

#129_John Hopkins University Medical Center

Baltimore, Maryland, United States

#143_Tufts Medical Center

Boston, Massachusetts, United States

#138_Massachusetts General Hospital

Boston, Massachusetts, United States

#119_Brigham and Women's Hospital

Boston, Massachusetts, United States

#115_Henry Ford Hospital

Detroit, Michigan, United States

#102_Mayo Clinic

Rochester, Minnesota, United States

#150_Saint Luke's Hospital

Kansas City, Missouri, United States

#104_Washington University School of Medicine

St Louis, Missouri, United States

#131_University of Nebraska Medical Center

Omaha, Nebraska, United States

#103_Weill Cornell Medical College

New York, New York, United States

#139_Icahn School of Medicine at Mount Sinai

New York, New York, United States

#133_Montefiore Medical Center

The Bronx, New York, United States

#147_Westchester Medical Center

Valhalla, New York, United States

#148_University of Cincinnati Medical Center

Cincinnati, Ohio, United States

#153_Cleveland Clinic

Cleveland, Ohio, United States

#101_The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

#145_The University of Toledo Medical Center

Toledo, Ohio, United States

#121_Integris Baptist Medical Center

Oklahoma City, Oklahoma, United States

#142_Penn State Heart and Vascular Institute

Hershey, Pennsylvania, United States

#140_Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

#134_Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

#130_University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

#141_Palmetto Health / Palmetto Heart

Columbia, South Carolina, United States

#151_Stern Cardiovascular Foundation

Memphis, Tennessee, United States

#146_Vanderbilt University Medical Center

Nashville, Tennessee, United States

#149_Seton Heart Institute

Austin, Texas, United States

#136_Baylor Health - Baylor University Medical Center

Dallas, Texas, United States

#107_Houston Methodist Hospital

Houston, Texas, United States

#122_Advanced Heart Failure Clinic - HCM

San Antonio, Texas, United States

#127_The University of Utah

Salt Lake City, Utah, United States

#114_University of Virginia

Charlottesville, Virginia, United States

#111_Inova Fairfax Hospital

Falls Church, Virginia, United States

#116_Virginia Commonwealth University (VCU) Medical Center

Richmond, Virginia, United States

#155_University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

Frantz RP, Desai SS, Ewald G, Franco V, Hage A, Horn EM, LaRue SJ, Mathier MA, Mandras S, Park MH, Ravichandran AK, Schilling JD, Wang IW, Zolty R, Rendon GG, Rocco MA, Selej M, Zhao C, Rame JE. SOPRANO: Macitentan in patients with pulmonary hypertension following left ventricular assist device implantation. Pulm Circ. 2024 Dec 4;14(4):e12446. doi: 10.1002/pul2.12446. eCollection 2024 Oct.

Reference Type: DERIVED

PMID: 39635465 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-055-205

Identifier Type: -

Identifier Source: org_study_id