Clinical Study to Assess the Long-term Safety, Tolerability, and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Phase 3

Terminated

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Macitentan 10 mg tablet, once daily.

• Registration Number: NCT01739400
• Lead Sponsor: Actelion

Brief Summary

Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of Eisenmenger syndrome.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-11-29
• Study First Submitted QC: 2012-11-29
• Study First Posted: 2012-12-03
• Study Start: 2013-09-10
• Primary Completion: 2018-01-12
• Study Completion: 2018-01-12
• Results First Submitted: 2019-01-09
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-26
• Last Update Submitted: 2019-03-26
• Results First Posted: 2019-04-16
• Last Update Posted: 2019-04-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 217

Inclusion Criteria

Subjects with ES (including those with Down Syndrome) having completed the double-blind AC-055-305 / MAESTRO study as scheduled, i.e., who remained in the double-blind study up to Week 16 (whether or not they were still taking study drug at the end of this period).

Exclusion Criteria

Subjects who prematurely discontinue double-blind study drug during the AC-055-305 / MAESTRO study due to:

• an AE assessed as related to the use of study drug,
• or elevated liver tests (related or unrelated to study drug).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Macitentan	Macitentan 10 mg tablet, once daily.	Macitentan 10 mg tablet, once daily.

Primary Outcome Measures

Name	Time	Method
Change in Borg Dyspnea Score at Month 6 and 12	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.	The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward.
Change in WHO Functional Class (FC) at Month 6 and 12	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.	Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward.
Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.	NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward.
Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.	No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT)

Trial Locations

Locations (51)

The General Hosp of Shenyang Military Region; 🇨🇳 Shenyang, Liaoning, China

Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult; 🇪🇸 Barcelona, Spain

Hanoi Medical University Hospital; 🇻🇳 Hanoi, Vietnam

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Gen Hosp Univ Vienna Dept Cardiology; 🇦🇹 Vienna, Austria

Hosp Cardiology Haut Leveque - Dept Congenital Diseases; 🇫🇷 Pessac, France

Ahepa University General Hospital; 🇬🇷 Thessaloniki, Greece

Cardiology Gdańsk Univ; 🇵🇱 Gdańsk, Poland

Mother and Child Health Care Institute Dr. Vukan Cupic; 🇷🇸 Belgrade, Serbia

Clin Hosp Ctr Zemun - Cardiology Dept; 🇷🇸 Belgrade, Serbia

Children'S Hospital, Ho Chi Minh; 🇻🇳 Ho Chi Minh, Vietnam

Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept; 🇧🇬 Sofia, Bulgaria

Unidad de Investigacion Clin En Med, Sc (Udicem); 🇲🇽 Monterrey, Nuevo Leon, Mexico

Instituto de Corazon de Querètaro; 🇲🇽 Querétaro, Mexico

Cardiology Kraków Univ; 🇵🇱 Krakow, Poland

Hosp Univ Coimbra - Dpt Cardiology; 🇵🇹 Coimbra, Portugal

Mhat Nat Card Hosp - Cardiology Clinic; 🇧🇬 Sofia, Bulgaria

Instituto Nacional de Cardiologia (Inc) Ignacio Chavez; 🇲🇽 Mexico City, Mexico

Cardiology Wrocław; 🇵🇱 Wrocław, Poland

Cardio Med Srl; 🇷🇴 Targu-Mures, Romania

Children'S Heart Center Nevada; 🇺🇸 Las Vegas, Nevada, United States

Mhat Sveta Anna Clin Card; 🇧🇬 Sofia, Bulgaria

Instituto Nacional del Torax; 🇨🇱 Providencia, Santiago RCH, Chile

Clinica Tabancura - Cardio Unit; 🇨🇱 Santiago, Chile

Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm; 🇷🇴 Timisoara, Romania

V. A. Almazov Institute of Cardiology; 🇷🇺 St Petersburg, Russian Federation

Dedinje Cardiovasc Inst - Cardiovasc Research Ctr; 🇷🇸 Belgrade, Serbia

Institut Jantung Negara; 🇲🇾 Kuala Lumpur, Malaysia

PHC, MAB; 🇵🇭 Manila, Philippines

Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii; 🇷🇴 Bucaresti, Romania

Tam Duc Hospital; 🇻🇳 Ho Chi Minh, Vietnam

Hosp Laennec - Dept Cardiology; 🇫🇷 Nantes Cedex 1, France

Russian Cardiology Scientific and Production Complex; 🇷🇺 Moscow, Russian Federation

Barnes-Jewish Hosp/Wash Univ School of Med; 🇺🇸 Saint Louis, Missouri, United States

Emory University Hospital/the Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

Texas Children'S Hosp - Dept of Cardiology; 🇺🇸 Houston, Texas, United States

Guangdong General Hospital, Cardiology Dpt; 🇨🇳 Guangzhou, Guangdong, China

Wu Han Asia Heart Hosp; 🇨🇳 Wuhan, Hubei, China

Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation; 🇨🇳 Shanghai, China

Cardiovascular Institute&Fuwai Hospital; 🇨🇳 Beijing, China

Hosp Pompidou - Dept Congenital Cardiac Diseases; 🇫🇷 Paris cedex 15, France

Beijing Anzhen Hospital, Cardiology Dpt; 🇨🇳 Beijing, China

Hosp La Timone - Dept Pediatric Cardiology; 🇫🇷 Marseille Cedex 5, France

Universitätsklinikum Giessen - Pediatric Heart Center; 🇩🇪 Giessen, Germany

Herzzentrum Berlin, Ped Cardiology; 🇩🇪 Berlin, Germany

Uni Heidelberg - Kinderkardiologie; 🇩🇪 Heidelberg, Germany

Hosp Sta Marta - Dept Cardiology; 🇵🇹 Lisboa, Portugal

Sci Institute Systemic Poriblems Cardio Diseases Kemerovo; 🇷🇺 Kemerovo, Russian Federation

Hosp Univ Virgen Macarena - Dpt Cardiology; 🇪🇸 Sevilla, Spain

Hosp Universitario La Fe Dpt Cardiology; 🇪🇸 Valencia, Spain

Bristol Univ Hosp Congenital Heart Centre; 🇬🇧 Bristol, United Kingdom