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

NCT ID: NCT03714815

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-07
• Study Completion Date: 2021-10-12

Brief 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). 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.

Conditions

Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open-label treatment period

oral administration of 10 mg macitentan once daily

Group Type: EXPERIMENTAL

macitentan 10 mg

Intervention Type: DRUG

macitentan 10 mg, film-coated tablet, oral use

Interventions

macitentan 10 mg

macitentan 10 mg, film-coated tablet, oral use

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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)

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

Sponsors

Almac Clinical Technologies

INDUSTRY

Sponsor Role: collaborator

Frontier Science & Technology Research Foundation, Inc.

INDUSTRY

Sponsor Role: collaborator

Covance

INDUSTRY

Sponsor Role: collaborator

Chiltern International Ltd.

INDUSTRY

Sponsor Role: collaborator

WorldCare Clinical, LLC

INDUSTRY

Sponsor Role: collaborator

AcitGraph

OTHER

Sponsor Role: collaborator

Medidata Solutions

INDUSTRY

Sponsor Role: collaborator

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Byra, MD

Role: STUDY_DIRECTOR

Actelion

Locations

South Denver Cardiology Associates PC

Littleton, Colorado, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

University Of Iowa - Hospitals & Clinics

Iowa City, Iowa, United States

University of Maryland

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University School Of Medicine

St Louis, Missouri, United States

Allegheny

Pittsburgh, Pennsylvania, United States

North Dallas Research Associates

McKinney, Texas, United States

Inova Heart and Vascular Institute

Falls Church, Virginia, United States

MultiCare Health System

Tacoma, Washington, United States

Aurora Saint Lukes Medical Center

Milwaukee, Wisconsin, United States

Instituto de Investigaciones Clinicas Mar del Plata

Mar del Plata, , Argentina

Medizinische Universitaet Wien

Vienna, , Austria

Maestri E Kormann Consultoria Médico- Científica Ltda

Blumenau, , Brazil

Instituto do Coracao de Marília

Marília, , Brazil

Diagnostic Consulting Center I Sliven

Sliven, , Bulgaria

Medical Centre Synexus

Sofia, , Bulgaria

Bispebjerg Og Frederiksberg Hospital

Copenhagen, , Denmark

CHU de Grenoble Hopital Albert Michallon

Grenoble, , France

Hopital de Bicetre

Le Kremlin-Bicêtre, , France

CHU Rouen Hopital Charles Nicolle

Rouen, , France

Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie

Dresden, , Germany

Universitaetsklinikum Giessen

Giessen, , Germany

Universitaetsklinikum Schleswig Holstein Campus Kiel

Kiel, , Germany

Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika

Budapest, , Hungary

Barzilai Medical Center

Ashkelon, , Israel

Hillel Yaffe Medical Center

Hadera, , Israel

Bnai Zion Medical Center

Haifa, , Israel

Galilee Medical Center

Nahariya, , Israel

Rabin Medical Center Beilinson Campus

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

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

Krakow, , Poland

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ

Lublin, , Poland

4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ

Wroclaw, , Poland

Cardiomed

Craiova, , Romania

SAL MED Pitesti

Piteşti, , Romania

Cmi Dr Podoleanu Cristian

Târgu Mureş, , Romania

Federal State Budget Scientific Institution

Kemerovo, , Russia

Moscow City Clinical Hospital No.51

Moscow, , Russia

Federal State Budgetary Institution

Saint Petersburg, , Russia

Ekaterinburg City Clinical Hospital #14

Yekaterinburg, , Russia

Sahlgrenska Universitetsjukhuset

Gothenburg, , Sweden

Royal Free Hospital

London, , United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United States; Argentina; Austria; Brazil; Bulgaria; Denmark; France; Germany; Hungary; Israel; Poland; Romania; Russia; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40066571 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001603-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-055G203

Identifier Type: -

Identifier Source: org_study_id