Clinical Study to Evaluate the Effects of Macitentan on Exercise Capacity in Subjects With Eisenmenger Syndrome

NCT01743001 | Completed Phase 3 Results DMC

• 1 other identifier: AC-055-305
• Study Type: interventional
• Target: 226
• Locations: 21 countries
• Sites: 55

Brief Summary

Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome.

Conditions

Pulmonary Arterial Hypertension

Keywords

exercise capacity; Eisenmenger Syndrome

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 16 in Exercise Capacity, as Measured by 6-minute Walk Distance (6MWD)

  The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.

  From baseline to Week 16

Secondary Outcomes (3)

• Change From Baseline to Week 16 in WHO Functional Class

  From baseline to Week 16

• Change From Baseline to Week 16 in Dyspnea, Assessed by the Borg Dyspnea Index

  From baseline to Week 16

• Change From Baseline to Week 16 in Quality of Life (QoL), Assessed by the Short Form-36 (SF-36) Questionnaire

  From baseline to Week 16

Study Arms (2)

Macitentan

EXPERIMENTAL

Subjects receive macitentan 10 mg oral tablet once daily

Drug: Macitentan 10 mg

Placebo

PLACEBO COMPARATOR

Subjects receive macitentan-matching placebo oral tablet once daily

Drug: Placebo

Interventions

Macitentan 10 mg DRUG

Macitentan 10 mg oral tablet once daily

Also known as: ACT-064992

Macitentan

Placebo DRUG

Macitentan-matching placebo oral tablet once daily

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects:
• not participating in the hemodynamic sub-study: males or females ≥ 12 years of age.
• participating in the hemodynamic sub-study: males or females ≥ 18 years of age.
• Subjects (including those with Down Syndrome \[DS\]) with confirmed Eisenmenger Syndrome \[ES\] (European Society of Cardiology \[ESC\] and the European Respiratory Society \[ERS\] guidelines):
• Established by echocardiography as:
• Large congenital shunting defect at atrial, ventricular or arterial level\*
• and right to left shunt or bi-directional shunt with prevalent right to left direction.
• Resting peripheral oxygen saturation (SpO2) ≤ 90% and \> 70% (pulse oximetry, room air).
• The lower limit is 65% if a subject is living at an altitude greater than 2500 m above sea level.
• \*Subjects with any of the following open defects are eligible for the study either as an isolated defect or in combination:
• atrial septal defect (ASD)
• ventricular septal defect (VSD)
• partial or complete atrioventricular septal defect (AVSD)
• patent ductus arteriosus (PDA)
• aortopulmonary window (AP window)

You may not qualify if:

• \- Main study and hemodynamic sub-study: Any of the following conditions previously known or identified via cardiac catheterization or echocardiography:
• Pulmonary arterial or venous stenosis \> 25% size of native pulmonary artery (PA) or pulmonary vein
• Severe tricuspid regurgitation in the setting of left to right shunt at the ventricular or atrial level
• Greater than mild tricuspid stenosis
• Intracavitary RV outflow obstruction
• Greater than mild mitral stenosis
• Intracavitary LV outflow obstruction
• Subvalvular or supravalvular aortic stenosis
• Aortic coarctation
• Greater than moderate mitral regurgitation
• Recognized extracardiac systemic venous collaterals to the pulmonary venous circulation
• Recognized hepatic wedge pressure-inferior vena cava pressure gradient \>12 mm Hg
• PCWP "v" waves \>20 mmHg
• Tetralogy of Fallot
• Truncus arteriosus

Sponsors & Collaborators

• Actelion: lead

Study Sites (55)

Ahmanson/UCLA Heart Disease Center

Los Angeles, California, 90095, United States

Location

Stanford Hospital and Clinic

Palo Alto, California, 94304, United States

Location

Emory University Hospital/the Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Barnes-Jewish Hosp/Wash Univ School of Med

St Louis, Missouri, 63110, United States

Location

Children'S Heart Center Nevada

Las Vegas, Nevada, 89109, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43210, United States

Location

Texas Children'S Hosp - Dept of Cardiology

Houston, Texas, 77030-2303, United States

Location

Gen Hosp Univ Vienna Dept Cardiology

Vienna, A-1090, Austria

Location

Mhat Nat Card Hosp - Cardiology Clinic

Sofia, 1309, Bulgaria

Location

Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept

Sofia, 1309, Bulgaria

Location

Mhat Sveta Anna Clin Card

Sofia, 1750, Bulgaria

Location

Inst Nat Torax, Unidad Cardiopatia Congenitas Del Adulto

Providencia, Chile

Location

Clinica Tabancura - Cardio Unit

Santiago, 7650018, Chile

Location

Guangdong General Hospital, Cardiology Dpt

Guangzhou, Guangdong, 510080, China

Location

Wu Han Asia Heart Hosp

Wuhan, Hubei, 430022, China

Location

The General Hosp of Shenyang Military Region

Shenyang, Liaoning, 110016, China

Location

Beijing Anzhen Hospital, Cardiology Dpt

Beijing, 100029, China

Location

Cardiovascular Institute&Fuwai Hospital

Beijing, 100037, China

Location

Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation

Shanghai, 200433, China

Location

Hosp La Timone - Dept Pediatric Cardiology

Marseille, 13385, France

Location

Hosp Laennec - Dept Cardiology

Nantes, 44093, France

Location

Hosp Pompidou - Dept Congenital Cardiac Diseases

Paris, 75908, France

Location

Hosp Cardiology Haut Leveque - Dept Congenital Diseases

Pessac, 33604, France

Location

Herzzentrum Berlin, Ped Cardiology

Berlin, 13353, Germany

Location

Universitätsklinikum Giessen - Pediatric Heart Center

Giessen, 35392, Germany

Location

Uni Heidelberg - Kinderkardiologie

Heidelberg, D-69120, Germany

Location

Ahepa University General Hospital

Thessaloniki, 54636, Greece

Location

Rabin Medical Centre - Pulmonology

Petach Tikvah, 49100, Israel

Location

Institut Jantung Negara

Kuala Lumpur, 50400, Malaysia

Location

Unidad de Investigacion Clin En Med, Sc (Udicem)

Monterrey, Nuevo León, 64718, Mexico

Location

Instituto Nacional de Cardiologia (Inc) Ignacio Chavez

Mexico City, 14080, Mexico

Location

Instituto de Corazon de Querètaro

Querétaro, Mexico

Location

PHC, MAB

Manila, Philippines

Location

Cardiology Gdańsk Univ

Gdansk, 80-952, Poland

Location

Cardiology Kraków Univ

Krakow, 31-202, Poland

Location

Cardiology Wrocław

Wroclaw, 51-124, Poland

Location

Hosp Univ Coimbra - Dpt Cardiology

Coimbra, 3000-075, Portugal

Location

Hosp Sta Marta - Dept Cardiology

Lisbon, 1169-024, Portugal

Location

Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii

Bucharest, 022328, Romania

Location

Cardio Med Srl

Târgu Mureş, 540136, Romania

Location

Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm

Timișoara, 300312, Romania

Location

Sci Institute Systemic Problems Cardio Diseases Kemerovo

Kemerovo, 650002, Russia

Location

Russian Cardiology Scientific and Production Complex

Moscow, 121552, Russia

Location

V. A. Almazov Institute of Cardiology

Saint Petersburg, 197341, Russia

Location

Dedinje Cardiovasc Inst - Cardiovasc Research Ctr

Belgrade, 11040, Serbia

Location

Mother and Child Health Care Inst "Dr Vukan Cupic"

Belgrade, 11070, Serbia

Location

Clin Hosp Ctr Zemun - Cardiology Dept

Belgrade, 11080, Serbia

Location

Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult

Barcelona, 08035, Spain

Location

Hosp Univ Virgen Macarena - Dpt Cardiology

Seville, 41007, Spain

Location

Hosp Universitario La Fe Dpt Cardiology

Valencia, 46009, Spain

Location

Omu Pediatry

Samsun, 55139, Turkey (Türkiye)

Location

Bristol Univ Hosp Congenital Heart Centre

Bristol, BS2 8BJ, United Kingdom

Location

Hanoi Medical University Hospital

Hanoi, Vietnam

Location

Children's Hospital, Ho Chi Minh

Ho Chi Minh City, Vietnam

Location

Tam Duc Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• Gatzoulis MA, Landzberg M, Beghetti M, Berger RM, Efficace M, Gesang S, He J, Papadakis K, Pulido T, Galie N; MAESTRO Study Investigators. Evaluation of Macitentan in Patients With Eisenmenger Syndrome. Circulation. 2019 Jan 2;139(1):51-63. doi: 10.1161/CIRCULATIONAHA.118.033575.

  PMID: 30586694 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Eisenmenger Complex

Interventions

macitentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Clinical Trial Disclosure Desk
• Organization: Actelion Pharmaceuticals Ltd

clinical-trials-disclosure@actelion.com

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 6, 2012
• Study Start: May 21, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 23, 2018
• Results First Posted: January 30, 2018

Record last verified: 2018-01

Locations

US (7); AU (1); CL (2); FR (4); ME (3); DE (3); BU (3); IL (1); RU (3); VN (3); PT (2); SE (3); RO (3); GR (1); PL (3); GB (1); ES (3); CN (6); TU (1); PH (1); MY (1)