Clinical trial NCT03153137: Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
Official title: Prospective, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Adult and Adolescent Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Heart Disease
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-05-15
Enrollment: 142
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to assess the effect of macitentan 10 mg as compared to placebo on exercise capacity through cardiopulmonary exercise testing.


Eligibility criteria: Inclusion Criteria:

* Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures
* Fontan-palliated subjects with either intra-atrial lateral tunnel total cavopulmonary connection (LT-TCPC), or extra cardiac tunnel TCPC (EC-TCPC) surgery \> 1 year before Screening. Either LT- or EC-TCPC can be primary or secondary to atrio-pulmonary connection
* New York Heart Association (NYHA) functional class (FC) II or III (assessed by the investigator using the Specific Activity Scale
* Women of childbearing potential must have a negative serum pregnancy test use reliable contraception

Exclusion Criteria:

* Pattern of Fontan circulation severity
* Deterioration of the Fontan-palliated condition.
* Limitations to Cardiopulmonary exercise testing (CPET)
* Peak VO2 \< 15 mL/kg/min.
* Any known factor or disease that may interfere with treatment compliance or full participation in the study

Primary outcomes:
measure: Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16
timeFrame: Baseline up to Week 16
Secondary outcomes:
measure: Change From Baseline in Peak VO2 Up to Week 52
timeFrame: Baseline up to Week 52
measure: Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16
timeFrame: Baseline up to Week 16
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Up to 56 weeks
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: Up to 56 weeks
measure: Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment
timeFrame: Up to 56 weeks
measure: Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Oxygen Saturation (SpO2)
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
timeFrame: Up to 56 weeks
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Hematocrit
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Erythrocytes and Reticulocytes
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Prothrombin Time
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Prothrombin International Normalized Ratio
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Bilirubin and Direct Bilirubin
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Gamma Glutamyl Transferase
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Creatinine
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Urea Nitrogen
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Urate
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Albumin and Protein
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Alpha Fetoprotein
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
measure: Change From Baseline in Cystatin C
timeFrame: Baseline, Week 8, Week 16, Week 32 and Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital Heart Center
state: Massachusetts
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Spokane
country: United States
facility: Providence Medical Research Providence Health Care
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital, Adult Congenital Heart Disease Unit
city: Parkville
country: Australia
facility: Royal Children's Hospital
city: South Brisbane
country: Australia
facility: Queensland CHILDREN'S HOSPITAL
city: Westmead
country: Australia
facility: Westmead Hospital
city: Quebec
country: Canada
facility: CHU de Quebec Universite Laval
city: Beijing
country: China
facility: Beijing Anzhen Hospital
city: Beijing
country: China
facility: Beijing Fuwai Hospital
city: Shanghai
country: China
facility: Shanghai Childrens Medical Center
city: Wuhan
country: China
facility: Wuhan Asia Heart Hospital
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Copenhagen
country: Denmark
facility: Rigshospitalet Kardiologisk Klinisk
city: Montpellier Cedex 5
country: France
facility: CHU Arnaud de Villeneuve
city: Paris
country: France
facility: Hôpital Necker - Enfants Malades
city: Pessac
country: France
facility: Hôpital Cardiologique Du Haut-Lévêque
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlinklinik Für Angeborene Herzfehler
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny We Wroclawiu
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
Study officials:
References: