Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects (RUBATO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03153137
Recruitment Status : Completed
First Posted : May 15, 2017
Results First Posted : September 13, 2022
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Congenital Heart Disease Drug: Macitentan 10 mg Drug: Placebo Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 14, 2017
Actual Primary Completion Date : June 30, 2021
Actual Study Completion Date : July 26, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Macitentan

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Macitentan
Macitentan 10 mg per day; film-coated tablet; oral use
 Drug: Macitentan 10 mg
film-coated tablet; oral use
Placebo Comparator: Placebo
film-coated tablet; oral use
 Drug: Placebo
film-coated tablet; oral use


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16 [ Time Frame: Baseline up to Week 16 ]
    Change from baseline in peak VO2 up to Week 16 was reported.


Secondary Outcome Measures :
  1. Change From Baseline in Peak VO2 Up to Week 52 [ Time Frame: Baseline up to Week 52 ]
    Change from baseline in peak VO2 up to Week 52 was reported.

  2. Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16 [ Time Frame: 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).

  3. Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: 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.

  4. Number of Participants With Treatment-emergent Adverse Events (AEs) [ Time Frame: 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.

  5. Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment [ Time Frame: 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.

  6. Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) [ Time Frame: 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.

  7. Change From Baseline in Pulse Rate [ Time Frame: 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.

  8. Change From Baseline in Oxygen Saturation (SpO2) [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in SpO2 was reported.

  9. Change From Baseline in Body Weight [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in body weight was reported.

  10. Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values [ Time Frame: 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".

  11. Change From Baseline in Hemoglobin [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in hemoglobin was reported.

  12. Change From Baseline in Hematocrit [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in hematocrit was reported.

  13. Change From Baseline in Erythrocytes and Reticulocytes [ Time Frame: 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.

  14. Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets [ Time Frame: 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.

  15. Change From Baseline in Prothrombin Time [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in prothrombin time was reported.

  16. Change From Baseline in Prothrombin International Normalized Ratio [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in prothrombin international normalized ratio was reported.

  17. Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP) [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in ALT, AST and AP were reported.

  18. Change From Baseline in Bilirubin and Direct Bilirubin [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in bilirubin and direct bilirubin was reported.

  19. Change From Baseline in Gamma Glutamyl Transferase [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in gamma glutamyl transferase was reported.

  20. Change From Baseline in Creatinine [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in creatinine was reported.

  21. Change From Baseline in Urea Nitrogen [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in urea nitrogen was reported.

  22. Change From Baseline in Urate [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in urate was reported.

  23. Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in glucose, cholesterol, triglycerides, sodium, potassium, chloride and calcium was reported.

  24. Change From Baseline in Albumin and Protein [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in albumin and protein was reported.

  25. Change From Baseline in Alpha Fetoprotein [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in alpha fetoprotein was reported.

  26. Change From Baseline in Cystatin C [ Time Frame: Baseline, Week 8, Week 16, Week 32 and Week 52 ]
    Change from baseline in cystatin C was reported.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03153137


Locations
Show Show 32 study locations
Sponsors and Collaborators
Actelion
  Study Documents (Full-Text)

Documents provided by Actelion:
Study Protocol  [PDF] November 19, 2020
Statistical Analysis Plan  [PDF] August 23, 2021

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT03153137    
Other Study ID Numbers: AC-055H301
2016-003320-23 ( EudraCT Number )
First Posted: May 15, 2017    Key Record Dates
Results First Posted: September 13, 2022
Last Update Posted: September 13, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
 Macitentan
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists