Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
- Registration Number
- NCT03153137
- Lead Sponsor
- Actelion
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 142
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Macitentan Macitentan 10 mg Macitentan 10 mg per day; film-coated tablet; oral use Placebo Placebo film-coated tablet; oral use
- Primary Outcome Measures
Name Time Method Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16 Baseline up to Week 16 Change from baseline in peak VO2 up to Week 16 was reported.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in glucose, cholesterol, triglycerides, sodium, potassium, chloride and calcium was reported.
Change From Baseline in Alpha Fetoprotein Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in alpha fetoprotein was reported.
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16 Baseline up to Week 16 Change from baseline in mean count per minute of daily PA-Ac up to Week 16 was reported. The daily physical activity (counts per min) of the participant was assessed via accelerometer during daytime. The accelerometer was given to the participant at Visit 1, and data was collected for 9 consecutive daily daytime periods after Visit 1 (baseline) to Visit 4 (Week 16).
Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment Up to 56 weeks Number of participants with AEs leading to premature discontinuation of study treatment was reported. AEs leading to premature discontinuation of study treatment were those with action taken with study drug reported as 'permanently discontinued' by the investigator.
Change From Baseline in Erythrocytes and Reticulocytes Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in erythrocytes and reticulocytes at Week 8, Week 16, Week 32 and Week 52 was reported.
Change From Baseline in Gamma Glutamyl Transferase Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in gamma glutamyl transferase was reported.
Change From Baseline in Albumin and Protein Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in albumin and protein was reported.
Change From Baseline in Peak VO2 Up to Week 52 Baseline up to Week 52 Change from baseline in peak VO2 up to Week 52 was reported.
Change From Baseline in Hemoglobin Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in hemoglobin was reported.
Change From Baseline in Hematocrit Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in hematocrit was reported.
Change From Baseline in Bilirubin and Direct Bilirubin Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in bilirubin and direct bilirubin was reported.
Change From Baseline in Creatinine Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in creatinine was reported.
Change From Baseline in Urate Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in urate was reported.
Change From Baseline in Cystatin C Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in cystatin C was reported.
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) Up to 56 weeks SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Change From Baseline in Pulse Rate Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in pulse rate at Week 8, Week 16, Week 32 and Week 52 was reported.
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets at Week 8, Week 16, Week 32 and Week 52 was reported.
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP) Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in ALT, AST and AP were reported.
Change From Baseline in Prothrombin Time Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in prothrombin time was reported.
Number of Participants With Treatment-emergent Adverse Events (AEs) Up to 56 weeks An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in systolic and diastolic arterial BP at Week 8, Week 16, Week 32 and Week 52 was reported.
Change From Baseline in Oxygen Saturation (SpO2) Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in SpO2 was reported.
Change From Baseline in Body Weight Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in body weight was reported.
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Up to 56 weeks Number of participants with treatment-emergent markedly laboratory abnormal laboratory values were reported. Abnormal values for platelets (LL \< 75); Lymphocytes (HH \> 4.0); Neutrophils (LL \< 1.5); Prothrombin International Normalized Ratio: HH (greater than and equal to \[\>=\] 1.5 upper limit of normal \[ULN\]), Ratio: HH \>= 2.5 ULN); Bilirubin (HH \>= 2 ULN); Alkaline Phosphatase (HH \> 2.5 ULN); Glomerular Filtration Rate (LL \< 60); Glucose (HH \> 8.9); Triglycerides (HH \> 3.42). Here "HH" refers to values above the normal range, where H stands for "high" and "LL" refers to values below the normal range where L stands for "low".
Change From Baseline in Prothrombin International Normalized Ratio Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in prothrombin international normalized ratio was reported.
Change From Baseline in Urea Nitrogen Baseline, Week 8, Week 16, Week 32 and Week 52 Change from baseline in urea nitrogen was reported.
Trial Locations
- Locations (32)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UCLA
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital Heart Center
🇺🇸Boston, Massachusetts, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Providence Medical Research Providence Health Care
🇺🇸Spokane, Washington, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
The Prince Charles Hospital, Adult Congenital Heart Disease Unit
🇦🇺Chermside, Australia
Royal Children's Hospital
🇦🇺Parkville, Australia
Queensland CHILDREN'S HOSPITAL
🇦🇺South Brisbane, Australia
Westmead Hospital
🇦🇺Westmead, Australia
CHU de Quebec Universite Laval
🇨🇦Quebec, Canada
Beijing Anzhen Hospital
🇨🇳Beijing, China
Beijing Fuwai Hospital
🇨🇳Beijing, China
Shanghai Childrens Medical Center
🇨🇳Shanghai, China
Wuhan Asia Heart Hospital
🇨🇳Wuhan, China
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Rigshospitalet Kardiologisk Klinisk
🇩🇰Copenhagen, Denmark
CHU Arnaud de Villeneuve
🇫🇷Montpellier Cedex 5, France
Hôpital Necker - Enfants Malades
🇫🇷Paris, France
Hôpital Cardiologique Du Haut-Lévêque
🇫🇷Pessac, France
Deutsches Herzzentrum Berlinklinik Für Angeborene Herzfehler
🇩🇪Berlin, Germany
Deutsches Herzzentrum München
🇩🇪München, Germany
Auckland City Hospital
🇳🇿Auckland, New Zealand
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Uniwersytecki Szpital Dzieciecy w Krakowie
🇵🇱Krakow, Poland
Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
🇵🇱Krakow, Poland
Wojewodzki Szpital Specjalistyczny We Wroclawiu
🇵🇱Wroclaw, Poland
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom