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Pulmonary HypertensionPhase 2SOPRANONCT02554903

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

A Phase 2 study testing Macitentan 10mg in people with Pulmonary Hypertension, run by Actelion at 50 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Hypertension
What is being tested?
Macitentan 10mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
57 participants
Where
50 sitesUnited States
Study dates
28 Mar 2016to 13 Mar 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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
  • 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.
  • Patient must be randomized within 14 days of Baseline RHC.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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).
  • Treatment with another investigational drug (planned, or taken) 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.

Trial locations and contacts

50 sites in 1 country.

50 sites in 1 country

United States50 sites
  • #149_Seton Heart Institute

    Austin, Texas, 78705

  • #129_John Hopkins University Medical Center

    Baltimore, Maryland, 21287

  • #106_Cedars-Sinai Medical Center

    Beverly Hills, California, 90211

  • #143_Tufts Medical Center

    Boston, Massachusetts, 02111

  • #138_Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • #119_Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • #114_University of Virginia

    Charlottesville, Virginia, 22905

  • #135_University of Chicago Medical Center

    Chicago, Illinois, 60637

  • #148_University of Cincinnati Medical Center

    Cincinnati, Ohio, 45242

  • #153_Cleveland Clinic

    Cleveland, Ohio, 44195

  • #141_Palmetto Health / Palmetto Heart

    Columbia, South Carolina, 29203

  • #101_The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • #136_Baylor Health - Baylor University Medical Center

    Dallas, Texas, 75226

  • #115_Henry Ford Hospital

    Detroit, Michigan, 48202

  • #111_Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • #142_Penn State Heart and Vascular Institute

    Hershey, Pennsylvania, 17033

  • #107_Houston Methodist Hospital

    Houston, Texas, 77030

  • #108_Indiana University Health Physicians Cardiology

    Indianapolis, Indiana, 46202

  • #112_St. Vincent Medical Group, Inc

    Indianapolis, Indiana, 46260

  • #120_University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • #150_Saint Luke's Hospital

    Kansas City, Missouri, 64111

  • #154_University of California San Diego

    La Jolla, California, 92037

  • #117_University of Louisville

    Louisville, Kentucky, 40202

  • #155_University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • #151_Stern Cardiovascular Foundation

    Memphis, Tennessee, 38120

  • #146_Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • #105_Ochsner Medical Center

    New Orleans, Louisiana, 70121

  • #103_Weill Cornell Medical College

    New York, New York, 10021

  • #139_Icahn School of Medicine at Mount Sinai

    New York, New York, 94080

  • #113_Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • #121_Integris Baptist Medical Center

    Oklahoma City, Oklahoma, 73112

  • #131_University of Nebraska Medical Center

    Omaha, Nebraska, 68918

  • #126_Florida Hospital

    Orlando, Florida, 32804

  • #140_Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • #125_Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • #134_Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • #130_University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • #116_Virginia Commonwealth University (VCU) Medical Center

    Richmond, Virginia, 23298

  • #102_Mayo Clinic

    Rochester, Minnesota, 55905

  • #110_Sutter Heart Institute

    Sacramento, California, 95819

  • #127_The University of Utah

    Salt Lake City, Utah, 84112

  • #122_Advanced Heart Failure Clinic - HCM

    San Antonio, Texas, 78229

  • #132_University of California San Francisco

    San Francisco, California, 94143

  • #104_Washington University School of Medicine

    St Louis, Missouri, 63110

  • #133_Montefiore Medical Center

    The Bronx, New York, 10467

  • #145_The University of Toledo Medical Center

    Toledo, Ohio, 43614

  • #144_University of Arizona

    Tucson, Arizona, 85724

  • #147_Westchester Medical Center

    Valhalla, New York, 10595

  • #123_MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

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

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.

Read more

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.

Being tested
Macitentan 10mg, Placebo sugar pill
Keywords
LVAD
Medical subject headings
Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Macitentan 10mgDrug

    Also called Active drug

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

  • Placebo sugar pillDrug

    Also called placebo comparator

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

Study groups in NCT02554903
Study groupRoleWhat they receive
Macitentan 10 mg poExperimentalApproximately 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.
Receives: Drug: Macitentan 10mg
Placebo sugar pillPlacebo comparatorApproximately 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.
Receives: Drug: Placebo sugar pill

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Week 12

Secondary outcomes (8)
  1. Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)

    mRAP was collected in the eCRF (electronic case record form). Right atrial pressure (RAP) is the blood pressure in the right atrium of the heart. Change from baseline to Week 12 in mRAP was measured at rest and no correction for multiple testing was applied.

    Measured: Baseline to Week 12

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

    mPAP was collected in the eCRF. The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Change from baseline to Week 12 in mPAP was measured at rest and no correction for multiple testing was applied.

    Measured: Baseline to Week 12

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

    PAWP was collected in the eCRF. PAWP is pressure within the pulmonary arterial system when the catheter tip is 'wedged' in the tapering branch of one of the pulmonary arteries. Change from baseline to Week 12 in PAWP was measured at rest and no correction for multiple testing was applied.

    Measured: Baseline to Week 12

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

    CI was calculated as Cardiac Output (CO)/body surface area (BSA), where CO is Thermodilution Cardiac Output (Liters per minute [L/min]) and BSA (m^2) equals to 0.007184*weight^0.425 (kilograms)*height^0.725 (centimeter). CI was represented in liters per minute per square meter (L/min/m^2). Change from baseline to Week 12 in CI was measured at rest and no correction for multiple testing was applied.

    Measured: Baseline to Week 12

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

    TPR was calculated as mPAP/CO where mPAP is mean pulmonary arterial pressure and CO is cardiac output. Change from baseline to Week 12 in TPR was calculated at rest and no correction for multiple testing was applied.

    Measured: Baseline to Week 12

  6. Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SvO2)

    Mixed venous oxygen saturation measures the end result of oxygen consumption and delivery. Change from baseline to Week 12 in SvO2 was reported and measured at rest and no correction for multiple testing was applied.

    Measured: Baseline to Week 12

  7. Change From Baseline to Week 12 in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Levels

    NT-proBNP levels in the blood are used for diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.

    Measured: Baseline to Week 12

  8. Change From Baseline to Week 12 in Participants World Health Organization (WHO) Functional Class (FC)

    WHO FC is a classification which reflects disease severity based on symptoms. WHO Functional Classification of pulmonary hypertension comprises of Class I (participants with pulmonary hypertension but without resulting limitation of physical activity), II (participants with pulmonary hypertension resulting in slight limitation of physical activity), III (participants with pulmonary hypertension resulting in marked limitation of physical activity) and IV (participants with pulmonary hypertension with inability to carry out any physical activity without symptoms). Change from baseline in WHO FC was reported. WHO FC was categorized as worsening (change greater than [>] 0); improvement (change less than [<] 0); or no change (change equals to [=] 0).

    Measured: Baseline to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2015 (estimated)
  2. Study start28 Mar 2016
  3. Primary completion13 Mar 2020
  4. Study completion13 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02554903
Sponsor's protocol ID
AC-055-205
Acronym
SOPRANO
Status last verified
Mar 2025
First submitted
8 Sep 2015
Last updated
30 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 39635465

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Macitentan 10mg in people with Pulmonary Hypertension, run by Actelion at 50 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pulmonary Vascular Resistance (PVR) Ratio of Week 12 to Baseline (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02554903, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.

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