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

NCT02554903 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AC-055-205
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 50

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

Keywords

LVAD

Outcome Measures

Primary Outcomes (1)

• Pulmonary Vascular Resistance (PVR) Ratio of Week 12 to Baseline

  PVR ratio equals to Week 12 PVR / Baseline PVR. PVR represents the resistance against which the right ventricle needs to pump. PVR was calculated using the following formula: mean pulmonary arterial pressure (mPAP) - pulmonary artery wedge pressure (PAWP)/cardiac output (CO); where mPAP and PAWP were measured at end-expiration and CO was measured in triplicate using the thermodilution method.

  Baseline to Week 12

Secondary Outcomes (8)

• Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)

  Baseline to Week 12

• Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)

  Baseline to Week 12

• Change From Baseline to Week 12 in Pulmonary Arterial Wedge Pressure (PAWP)

  Baseline to Week 12

• Change From Baseline to Week 12 in Cardiac Index (CI)

  Baseline to Week 12

• Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR)

  Baseline to Week 12

Study Arms (2)

Macitentan 10 mg po

EXPERIMENTAL

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

Placebo sugar pill

PLACEBO COMPARATOR

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

Interventions

Macitentan 10mg DRUG

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

Also known as: Active drug

Macitentan 10 mg po

Placebo sugar pill DRUG

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

Also known as: placebo comparator

Placebo sugar pill

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent prior to initiation of any study-mandated procedure.
• Males or females ≥ 18 years of age.
• Surgical implantation of LVAD within 90 days prior to Randomization.
• 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:
• Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
• Pulmonary artery wedge pressure (PAWP) ≤ 18 mmHg and
• PVR \> 3 Wood units.
• Stabilization of the patient for 48 h prior to the Baseline RHC, defined as:
• No LVAD pump speed/flow rate changes and
• Stable dose of oral diuretics and
• No intravenous (i.v.) inotropes or vasopressors and
• Patient able to ambulate.
• A woman of childbearing potential is eligible only if she has:
• A negative serum pregnancy test result during the Screening period (Visit 1) and Randomization (Visit 2) and
• Agreement to undertake monthly serum pregnancy tests during the study and up to 30 days after study treatment discontinuation and

You may not qualify if:

• 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.
• 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, i.v., subcutaneous (s.c.), or oral prostanoids, or guanylate cyclase stimulators within 7 days prior to Baseline RHC or study treatment initiation.
• Treatment with inhaled prostanoids (e.g., iloprost, epoprostenol) or nitric oxide within 24 h prior to Baseline RHC or study treatment initiation.
• 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).

Sponsors & Collaborators

• Actelion: lead

Study Sites (50)

#125_Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

#144_University of Arizona

Tucson, Arizona, 85724, United States

Location

#106_Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

#154_University of California San Diego

La Jolla, California, 92037, United States

Location

#110_Sutter Heart Institute

Sacramento, California, 95819, United States

Location

#132_University of California San Francisco

San Francisco, California, 94143, United States

Location

#123_MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

#126_Florida Hospital

Orlando, Florida, 32804, United States

Location

#135_University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

#113_Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

#108_Indiana University Health Physicians Cardiology

Indianapolis, Indiana, 46202, United States

Location

#112_St. Vincent Medical Group, Inc

Indianapolis, Indiana, 46260, United States

Location

#120_University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

#117_University of Louisville

Louisville, Kentucky, 40202, United States

Location

#105_Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

#129_John Hopkins University Medical Center

Baltimore, Maryland, 21287, United States

Location

#143_Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

#138_Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

#119_Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

#115_Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

#102_Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

#150_Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

#104_Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

#131_University of Nebraska Medical Center

Omaha, Nebraska, 68918, United States

Location

#103_Weill Cornell Medical College

New York, New York, 10021, United States

Location

#139_Icahn School of Medicine at Mount Sinai

New York, New York, 94080, United States

Location

#133_Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

#147_Westchester Medical Center

Valhalla, New York, 10595, United States

Location

#148_University of Cincinnati Medical Center

Cincinnati, Ohio, 45242, United States

Location

#153_Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

#101_The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

#145_The University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

#121_Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

#142_Penn State Heart and Vascular Institute

Hershey, Pennsylvania, 17033, United States

Location

#140_Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

#134_Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

#130_University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

#141_Palmetto Health / Palmetto Heart

Columbia, South Carolina, 29203, United States

Location

#151_Stern Cardiovascular Foundation

Memphis, Tennessee, 38120, United States

Location

#146_Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

#149_Seton Heart Institute

Austin, Texas, 78705, United States

Location

#136_Baylor Health - Baylor University Medical Center

Dallas, Texas, 75226, United States

Location

#107_Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

#122_Advanced Heart Failure Clinic - HCM

San Antonio, Texas, 78229, United States

Location

#127_The University of Utah

Salt Lake City, Utah, 84112, United States

Location

#114_University of Virginia

Charlottesville, Virginia, 22905, United States

Location

#111_Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

#116_Virginia Commonwealth University (VCU) Medical Center

Richmond, Virginia, 23298, United States

Location

#155_University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 39635465 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

macitentan; Bulk Drugs

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Limitations and Caveats

A limitation of this study was its slow enrollment and a final sample size that was less than the predefined target.

Results Point of Contact

• Title: Medical Affairs Associate Director
• Organization: Actelion Pharmaceuticals US, Inc

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Mark Rocco

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 18, 2015
• Study Start: March 28, 2016
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: March 30, 2025
• Results First Posted: April 1, 2021

Record last verified: 2025-03

Locations

US (50)