Clinical trial NCT03714815: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease
Keywords: pulmonary vascular disease
macitentan
heart failure with preserved ejection fraction
Lead sponsor: Actelion
Sponsor class: INDUSTRY
Collaborators: name: Almac Clinical Technologies
name: Frontier Science & Technology Research Foundation, Inc.
name: Covance
name: Chiltern International Ltd.
name: WorldCare Clinical, LLC
name: AcitGraph
name: Medidata Solutions
First posted: 2018-10-22
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Number of Participants With All-cause Deaths up to 30 Days After Study Treatment Discontinuation
timeFrame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)
measure: Number of Participants With All-cause Hospital Admissions up to 30 Days After Study Treatment Discontinuation
timeFrame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) up to 30 Days After Study Treatment Discontinuation
timeFrame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)
measure: Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
timeFrame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)
measure: Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Pulse Rate at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Pulse Rate at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Body Weight at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Body Weight at Week 52
timeFrame: Baseline and Week 52
measure: Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation
timeFrame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)
measure: Change From Baseline in Hemoglobin at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Hemoglobin at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Leukocytes and Platelets at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Leukocytes and Platelets at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Bilirubin at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Bilirubin at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
timeFrame: Baseline and Week 52
Secondary outcomes:
Other outcomes:
Locations:
city: Littleton
country: United States
facility: South Denver Cardiology Associates PC
state: Colorado
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University Of Iowa - Hospitals & Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Pittsburgh
country: United States
facility: Allegheny
state: Pennsylvania
city: McKinney
country: United States
facility: North Dallas Research Associates
state: Texas
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
city: Milwaukee
country: United States
facility: Aurora Saint Lukes Medical Center
state: Wisconsin
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
city: Vienna
country: Austria
facility: Medizinische Universitaet Wien
city: Blumenau
country: Brazil
facility: Maestri E Kormann Consultoria Médico- Científica Ltda
city: Marilia
country: Brazil
facility: Instituto do Coracao de Marília
city: Sliven
country: Bulgaria
facility: Diagnostic Consulting Center I Sliven
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus
city: Copenhagen
country: Denmark
facility: Bispebjerg Og Frederiksberg Hospital
city: Grenoble Cedex 9
country: France
facility: CHU de Grenoble Hopital Albert Michallon
city: Le Kremlin Bicetre
country: France
facility: Hopital de Bicetre
city: Rouen Cedex
country: France
facility: CHU Rouen Hopital Charles Nicolle
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig Holstein Campus Kiel
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center Beilinson Campus
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
city: Wroclaw
country: Poland
facility: 4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ
city: Craiova
country: Romania
facility: Cardiomed
city: Pitesti
country: Romania
facility: SAL MED Pitesti
city: Targu-Mures
country: Romania
facility: Cmi Dr Podoleanu Cristian
city: Ekaterinburg
country: Russian Federation
facility: Ekaterinburg City Clinical Hospital #14
city: Kemerovo
country: Russian Federation
facility: Federal State Budget Scientific Institution
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital No.51
city: St Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetsjukhuset
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Study officials:
affiliation: Actelion
name: William Byra, MD
role: STUDY_DIRECTOR
References: