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

Pulmonary Arterial Hypertension Clinical Trial

— MAESTRO-OL  

Official title:

Long Term, Single-arm, Open-label Extension Study of Protocol AC-055-305 to Assess the Safety, Tolerability and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01739400
• Other study ID #: AC-055-308
• Status: Terminated
• Phase: Phase 3
• Start date: September 10, 2013
• Est. completion date: January 12, 2018

Study information

• Verified date: March 2019
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 217
• Est. completion date: January 12, 2018
• Est. primary completion date: January 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Eisenmenger Complex
• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Macitentan 10 mg tablet, once daily.
Macitentan 10 mg tablet, once daily.

Locations

Country	Name	City	State
Austria	Gen Hosp Univ Vienna Dept Cardiology	Vienna
Bulgaria	Mhat Nat Card Hosp - Cardiology Clinic	Sofia
Bulgaria	Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept	Sofia
Bulgaria	Mhat Sveta Anna Clin Card	Sofia
Chile	Instituto Nacional del Torax	Providencia	Santiago RCH
Chile	Clinica Tabancura - Cardio Unit	Santiago
China	Beijing Anzhen Hospital, Cardiology Dpt	Beijing
China	Cardiovascular Institute&Fuwai Hospital	Beijing
China	Guangdong General Hospital, Cardiology Dpt	Guangzhou	Guangdong
China	Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation	Shanghai
China	The General Hosp of Shenyang Military Region	Shenyang	Liaoning
China	Wu Han Asia Heart Hosp	Wuhan	Hubei
France	Hosp La Timone - Dept Pediatric Cardiology	Marseille Cedex 5
France	Hosp Laennec - Dept Cardiology	Nantes Cedex 1
France	Hosp Pompidou - Dept Congenital Cardiac Diseases	Paris cedex 15
France	Hosp Cardiology Haut Leveque - Dept Congenital Diseases	Pessac
Germany	Herzzentrum Berlin, Ped Cardiology	Berlin
Germany	Universitätsklinikum Giessen - Pediatric Heart Center	Giessen
Germany	Uni Heidelberg - Kinderkardiologie	Heidelberg
Greece	Ahepa University General Hospital	Thessaloniki
Malaysia	Institut Jantung Negara	Kuala Lumpur
Mexico	Instituto Nacional de Cardiologia (Inc) Ignacio Chavez	Mexico City
Mexico	Unidad de Investigacion Clin En Med, Sc (Udicem)	Monterrey	Nuevo Leon
Mexico	Instituto de Corazon de Querètaro	Querétaro
Philippines	PHC, MAB	Manila
Poland	Cardiology Gdansk Univ	Gdansk
Poland	Cardiology Kraków Univ	Krakow
Poland	Cardiology Wroclaw	Wroclaw
Portugal	Hosp Univ Coimbra - Dpt Cardiology	Coimbra
Portugal	Hosp Sta Marta - Dept Cardiology	Lisboa
Romania	Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii	Bucaresti
Romania	Cardio Med Srl	Targu-Mures
Romania	Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm	Timisoara
Russian Federation	Sci Institute Systemic Poriblems Cardio Diseases Kemerovo	Kemerovo
Russian Federation	Russian Cardiology Scientific and Production Complex	Moscow
Russian Federation	V. A. Almazov Institute of Cardiology	St Petersburg
Serbia	Clin Hosp Ctr Zemun - Cardiology Dept	Belgrade
Serbia	Dedinje Cardiovasc Inst - Cardiovasc Research Ctr	Belgrade
Serbia	Mother and Child Health Care Institute Dr. Vukan Cupic	Belgrade
Spain	Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult	Barcelona
Spain	Hosp Univ Virgen Macarena - Dpt Cardiology	Sevilla
Spain	Hosp Universitario La Fe Dpt Cardiology	Valencia
United Kingdom	Bristol Univ Hosp Congenital Heart Centre	Bristol
United States	Emory University Hospital/the Emory Clinic	Atlanta	Georgia
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Texas Children'S Hosp - Dept of Cardiology	Houston	Texas
United States	Children'S Heart Center Nevada	Las Vegas	Nevada
United States	Barnes-Jewish Hosp/Wash Univ School of Med	Saint Louis	Missouri
Vietnam	Hanoi Medical University Hospital	Hanoi
Vietnam	Children'S Hospital, Ho Chi Minh	Ho Chi Minh
Vietnam	Tam Duc Hospital	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Vietnam,  Austria,  Bulgaria,  Chile,  China,  France,  Germany,  Greece,  Malaysia,  Mexico,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12	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.	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Primary	Change in WHO Functional Class (FC) at Month 6 and 12	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.	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Primary	Change in Borg Dyspnea Score at Month 6 and 12	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.	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Primary	Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12	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)	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.