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Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular DiseasePhase 2SERENADE OLNCT03714815

A Long Term Study to Find Out if Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

A Phase 2 study testing macitentan 10 mg in people with Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease, run by Actelion at 44 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The aim of this open-label (OL) extension trial is to study the long-term safety and efficacy of macitentan in subjects with heart failure with preserved ejection fraction (HFpEF) and pulmonary vascular disease (PVD) beyond the treatment in the double-blind parent SERENADE study (AC-055G202, NCT03153111). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
macitentan 10 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
44 sitesin 15 countries
Study dates
7 Dec 2018to 12 Oct 2021
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

  • Signed and dated Informed Consent Form (ICF).
  • Participant remained in the main study (SERENADE/AC-055G202, NCT03153111) for: a) 52 weeks after randomization if entered this Open-label (OL) extension study prior to protocol Version 4, b) At least 24 weeks after randomization if entering this OL extension study under protocol Version 4
  • A woman of childbearing potential is eligible only if: (1) Negative pre-treatment serum pregnancy test; (2) Agreement to undertake monthly pregnancy tests from the enrollment visit up to at least 30 days after study treatment discontinuation; and (2) Agreement to use reliable contraception from at least 30 days prior to the enrollment visit up to at least 30 days after study treatment discontinuation.

Who cannot join

  • Premature discontinuation of study treatment in the main study (SERENADE/AC-055G202, NCT03153111) due to an adverse event related to: (1) Edema or fluid retention; (2) Worsening of heart failure; (3) Liver aminotransferase elevation; and (4) Study treatment, based on investigators' discretion
  • Liver aminotransferase elevations, at the enrollment visit, fulfilling the following criteria: (1) Alanine amino transferase (ALT) / aspartate aminotransferase (AST) greater than or equal to (>=) 8 * the upper limit of normal (ULN); (2) ALT/AST >= 3 * ULN and associated clinical symptoms of liver injury, for example: nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue, flu-like syndrome (arthralgia, myalgia, fever); and (3) ALT/AST >= 3 * ULN and associated increase in total bilirubin to >= 2 * ULN
  • Treatment with the following forbidden medications within 1 month prior to the enrollment visit: (1) Treatments that may interfere with the assessment of efficacy (that is, endothelin receptor antagonists, prostanoids, phosphodiesterase-5 inhibitors, guanylate cyclase stimulators); (2) Strong cytochrome P-450 3A4 (CYP3A4) inducers such as rifabutin, rifampin, rifampicin, rifapentin, carbamazepine, phenobarbital, phenytoin, or St. John's wort; (3) Strong CYP3A4 inhibitors such as ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir or a moderate dual CYP3A4/CYP2C9 inhibitor (for example, fluconazole or amiodarone) or co-administration of a combination of moderate CYP3A4 (for example, ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitors (for example, miconazole, piperine), in the 1-month period prior to baseline. This will not necessarily apply to participants who are already well-managed on such an ongoing combination; and (4) any other investigational treatment
  • Pregnant, planning to be become pregnant or lactating.
  • Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
  • Known hypersensitivity to macitentan or drugs of the same class, or any of the study drug excipients (for example, soy lecithin, lactose)

Trial locations and contacts

44 sites in 15 countries.

44 sites in 15 countries

United States11 sites

  • University of Maryland

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

  • Inova Heart and Vascular Institute

    Falls Church, Virginia, 22042

  • University Of Iowa - Hospitals & Clinics

    Iowa City, Iowa, 52242-1081

  • South Denver Cardiology Associates PC

    Littleton, Colorado, 80120

  • North Dallas Research Associates

    McKinney, Texas, 75069

  • Aurora Saint Lukes Medical Center

    Milwaukee, Wisconsin, 53215

  • Allegheny

    Pittsburgh, Pennsylvania, 15212

  • Washington University School Of Medicine

    St Louis, Missouri, 63110

  • MultiCare Health System

    Tacoma, Washington, 98405

Other trials in United States

Israel6 sites

  • Barzilai Medical Center

    Ashkelon

  • Hillel Yaffe Medical Center

    Hadera, 3810101

  • Bnai Zion Medical Center

    Haifa, 3339419

  • Galilee Medical Center

    Nahariya, 2210001

  • Rabin Medical Center Beilinson Campus

    Petah Tikva, 4941492

  • Kaplan Medical Center

    Rehovot, 7610001

Other trials in Israel

Russia4 sites

  • Federal State Budget Scientific Institution

    Kemerovo, 650002

  • Moscow City Clinical Hospital No.51

    Moscow, 121309

  • Federal State Budgetary Institution

    Saint Petersburg, 197341

  • Ekaterinburg City Clinical Hospital #14

    Yekaterinburg, 620039

Other trials in Russia

France3 sites

  • CHU de Grenoble Hopital Albert Michallon

    Grenoble

  • Hopital de Bicetre

    Le Kremlin-Bicêtre, 94270

  • CHU Rouen Hopital Charles Nicolle

    Rouen, 76031

Other trials in France

Germany3 sites

  • Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie

    Dresden, 01307

  • Universitaetsklinikum Giessen

    Giessen, 35392

  • Universitaetsklinikum Schleswig Holstein Campus Kiel

    Kiel, 24105

Other trials in Germany

Poland3 sites

  • Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn

    Krakow, 31 202

  • Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ

    Lublin, 20 718

  • 4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ

    Wroclaw, 50 513

Other trials in Poland

Romania3 sites

  • Cardiomed

    Craiova, 200505

  • SAL MED Pitesti

    Piteşti, 110437

  • Cmi Dr Podoleanu Cristian

    Târgu Mureş, 540503

Other trials in Romania

Brazil2 sites

  • Maestri E Kormann Consultoria Médico- Científica Ltda

    Blumenau, 89020-430

  • Instituto do Coracao de Marília

    Marília, 17515-000

Other trials in Brazil

Bulgaria2 sites

  • Diagnostic Consulting Center I Sliven

    Sliven, 8800

  • Medical Centre Synexus

    Sofia, 1784

Other trials in Bulgaria

United Kingdom2 sites

  • Royal Free Hospital

    London, NW3 2QG

  • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

    Sheffield, S10 2RX

Other trials in United Kingdom

Argentina1 site

  • Instituto de Investigaciones Clinicas Mar del Plata

    Mar del Plata, B7600FZN

Other trials in Argentina

Austria1 site

  • Medizinische Universitaet Wien

    Vienna, 1090

Other trials in Austria

Denmark1 site

  • Bispebjerg Og Frederiksberg Hospital

    Copenhagen, 2400

Other trials in Denmark

Hungary1 site

  • Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika

    Budapest, 1122

Other trials in Hungary

Sweden1 site

  • Sahlgrenska Universitetsjukhuset

    Gothenburg, 413 45

Other trials in Sweden

About this study

Official title: A Long-term, Multicenter, Single-arm, Open-label Extension of the SERENADE Study, to Assess the Safety and Efficacy of Macitentan in Subjects With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

The aim of this open-label (OL) extension trial is to study the long-term safety and efficacy of macitentan in subjects with heart failure with preserved ejection fraction (HFpEF) and pulmonary vascular disease (PVD) beyond the treatment in the double-blind parent SERENADE study (AC-055G202, NCT03153111). Furthermore, this OL extension study will give eligible subjects of the main study (SERENADE/AC-055G202, NCT03153111) an opportunity to continue or start receiving macitentan.

Being tested
macitentan 10 mg
Keywords
pulmonary vascular disease, macitentan, heart failure with preserved ejection fraction

What participants receive

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

  • macitentan 10 mgDrug

    macitentan 10 mg, film-coated tablet, oral use

Study groups in NCT03714815
Study groupRoleWhat they receive
Open-label treatment periodExperimentaloral administration of 10 mg macitentan once daily
Receives: Drug: macitentan 10 mg

What is being measured

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

  1. Number of Participants With All-cause Deaths up to 30 Days After Study Treatment Discontinuation

    Number of participants with all-cause deaths up to 30 days after study treatment discontinuation were reported. All-cause deaths are defined as all anticipated and unanticipated deaths due to any cause.

    Measured: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

  2. Number of Participants With All-cause Hospital Admissions up to 30 Days After Study Treatment Discontinuation

    Number of participants with all-cause hospital admissions up to 30 days after study treatment discontinuation were reported.

    Measured: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

  3. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) up to 30 Days After Study Treatment Discontinuation

    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is a suspected transmission of any infectious agent via a medicinal product, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any AE and SAE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) within the analysis set was considered to be treatment-emergent.

    Measured: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

  4. Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment

    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT within the analysis set was considered to be treatment-emergent.

    Measured: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

  5. Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 24

    Change from baseline in systolic and diastolic arterial BP at Week 24 was reported.

    Measured: Baseline and Week 24

  6. Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 52

    Change from baseline in systolic and diastolic arterial BP at Week 52 was reported.

    Measured: Baseline and Week 52

  7. Change From Baseline in Pulse Rate at Week 24

    Change from baseline in pulse rate at Week 24 was reported.

    Measured: Baseline and Week 24

  8. Change From Baseline in Pulse Rate at Week 52

    Change from baseline in pulse rate at Week 52 was reported.

    Measured: Baseline and Week 52

  9. Change From Baseline in Body Weight at Week 24

    Change from baseline in body weight at Week 24 was reported.

    Measured: Baseline and Week 24

  10. Change From Baseline in Body Weight at Week 52

    Change from baseline in body weight at Week 52 was reported.

    Measured: Baseline and Week 52

  11. Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation

    Number of participants with treatment-emergent MLAs (Hemoglobin [grams/Liter{L}], Hematocrit [L/L], Leukocytes [10^9cells/L], Lymphocytes [10^9cells/L], Alanine Aminotransferase [Units/L {U/L}], Aspartate Aminotransferase [U/L], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Creatinine [mcmol/L], Urea Nitrogen [mmol/L], Urate [mcmol/L], Potassium [mmol/L], Sodium [mmol/L], Magnesium [mmol/L], Calcium [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Here, > signifies greater than; < signifies less than; ULN signifies upper limit of normal; and L=Low, H=High, LL=low/low, HH=high/high, LLL=lower/worse than LL, HHH=higher/worse than HH.

    Measured: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

  12. Change From Baseline in Hemoglobin at Week 24

    Change from baseline in hemoglobin at Week 24 was reported.

    Measured: Baseline and Week 24

  13. Change From Baseline in Hemoglobin at Week 52

    Change from baseline in hemoglobin at Week 52 was reported.

    Measured: Baseline and Week 52

  14. Change From Baseline in Leukocytes and Platelets at Week 24

    Change from baseline in leukocytes and platelets at Week 24 was reported.

    Measured: Baseline and Week 24

  15. Change From Baseline in Leukocytes and Platelets at Week 52

    Change from baseline in leukocytes and platelets at Week 52 was reported.

    Measured: Baseline and Week 52

  16. Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 24

    Change from baseline in alanine aminotransferase and aspartate aminotransferase at Week 24 was reported.

    Measured: Baseline and Week 24

  17. Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 52

    Change from baseline in alanine aminotransferase and aspartate aminotransferase at Week 52 was reported.

    Measured: Baseline and Week 52

  18. Change From Baseline in Bilirubin at Week 24

    Change from baseline in bilirubin at Week 24 was reported.

    Measured: Baseline and Week 24

  19. Change From Baseline in Bilirubin at Week 52

    Change from baseline in bilirubin at Week 52 was reported.

    Measured: Baseline and Week 52

  20. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24

    Change from baseline in eGFR rate at Week 24 was reported.

    Measured: Baseline and Week 24

  21. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52

    Change from baseline in eGFR rate at Week 52 was reported.

    Measured: Baseline and Week 52

Timeline

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

  1. First posted22 Oct 2018
  2. Study start7 Dec 2018
  3. Primary completion12 Oct 2021
  4. Study completion12 Oct 2021

Why it stopped: the absence of a positive trend in all efficacy parameters indicates that macitentan 10 mg does not have a beneficial effect in patients with HFpEF and PVD.

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
Not applicable
Intervention model
Single group
Model description
Subjects who remained in main study (SERENADE/AC-055G202, NCT03153111) after randomization and who meet the eligibility criteria described will be eligible to enter this single-arm OL extension study. All enrolled subjects will receive macitentan 10 mg. For this OL extension study no primary efficacy endpoint has been defined and all efficacy endpoints are of exploratory nature. The ones listed below are considered safety endpoints.
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03714815
Sponsor's protocol ID
AC-055G203
Other IDs
2018-001603-37, 2018
Acronym
SERENADE OL
Status last verified
Jan 2025
First submitted
19 Oct 2018
Last updated
4 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials\\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu

Publications

  • Shah SJ, Bonderman D, Borlaug BA, Cleland JGF, Lack G, Lu W, Voors AA, Zannad F, Gladwin MT. Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study. Circ Heart Fail. 2025 Mar;18(3):e011381. doi: 10.1161/CIRCHEARTFAILURE.123.011381. Epub 2025 Mar 11.

    PubMed 40066571

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing macitentan 10 mg in people with Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease, run by Actelion at 44 sites in 15 countries.

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 3 inclusion and 6 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: stopped early, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States, Israel, Russia, France, Germany and 10 more countries. 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. 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 4 Nov 2022). 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?

Number of Participants With All-cause Deaths up to 30 Days After Study Treatment Discontinuation (time frame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)). The study lists 21 primary outcomes in all. 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 NCT03714815, 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 4 Feb 2025.

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