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Trial record 1 of 29 for:    macitentan | Pulmonary Artery Hypertension
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REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension (REPAIR)

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: NCT02310672
Recruitment Status : Completed
First Posted : December 8, 2014
Results First Posted : September 24, 2020
Last Update Posted : September 24, 2020
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE December 4, 2014
First Posted Date  ICMJE December 8, 2014
Results First Submitted Date  ICMJE September 3, 2020
Results First Posted Date  ICMJE September 24, 2020
Last Update Posted Date September 24, 2020
Actual Study Start Date  ICMJE June 1, 2015
Actual Primary Completion Date September 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2020)
  • Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26 [ Time Frame: Baseline and Week 26 ]
    Change from baseline in RVSV assessed by cardiac magnetic resonance imaging (MRI) from pulmonary artery flow was reported at Week 26. Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.
  • Ratio of Week 26 to Baseline Pulmonary Vascular Resistance (PVR) [ Time Frame: Baseline and Week 26 ]
    Ratio of Week 26 to baseline PVR as assessed by RHC was reported. PVR represents the resistance against which the right ventricle needs to pump. PVR is determined by right heart catheterization (RHC). PVR was calculated as 80*(Mean pulmonary arterial pressure [mPAP] -[Pulmonary capillary wedge pressure {PCWP} or Left ventricular end diastolic pressure {LVEDP} if PCWP not available/cardiac output [CO]). Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2014)
To evaluate the effect of macitentan on right ventricular and hemodynamic properties in patients with symptomatic pulmonary arterial hypertension (PAH). [ Time Frame: Baseline to Week 26 ]
Change in Right Ventricular Stroke Volume and ratio of Week 26 to baseline PVR
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2020)
  • Change From Baseline in Right Ventricular End Diastolic Volume (RVEDV) to Week 26 [ Time Frame: Baseline to Week 26 ]
    Change from baseline to Week 26 in RVEDV assessed by cardiac MRI was reported.
  • Change From Baseline in Right Ventricular End Systolic Volume (RVESV) to Week 26 [ Time Frame: Baseline to Week 26 ]
    Change from baseline to Week 26 in RVESV assessed by cardiac MRI was reported.
  • Change From Baseline in Right Ventricular Ejection Fraction (RVEF) to Week 26 (% Blood Volume) [ Time Frame: Baseline to Week 26 ]
    Change from baseline to Week 26 in RVEF based on pulmonary artery flow assessed by cardiac MRI was reported.
  • Change From Baseline in Right Ventricle (RV) Mass to Week 26 [ Time Frame: Baseline to Week 26 ]
    Change from baseline to Week 26 in RV mass assessed by cardiac MRI was reported.
  • Change From Baseline in Six-minutes Walk Distance (6MWD) to Week 26 [ Time Frame: Baseline to Week 26 ]
    6MWD is a non-encouraged test performed in a 30 meter (m) long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. This test is used to assess exercise capacity. The test was performed about 30 minutes after study drug administration. Any increase in the walk distance was considered improvement from baseline.
  • Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26 [ Time Frame: Baseline to Week 26 ]
    WHO FC is a classification which reflects disease severity based on symptoms. WHO Functional Classification of pulmonary hypertension comprises of Class I (participants with pulmonary hypertension but without resulting limitation of physical activity), II (participants with pulmonary hypertension resulting in slight limitation of physical activity), III (participants with pulmonary hypertension resulting in marked limitation of physical activity) and IV (participants with pulmonary hypertension with inability to carry out any physical activity without symptoms). Changes from baseline to Week 26 included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or unchanged/stable (same FC at baseline and at the post-baseline time point).
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2014)
  • To investigate the effect of macitentan on ventriculo-arterial coupling in patients with symptomatic PAH. [ Time Frame: Baseline to Week 26 ]
    Change in arterial elastance
  • To evaluate the safety and tolerability of macitentan in patients with symptomatic PAH. [ Time Frame: Base line to 30 days after End of Treatment (Week 52) ]
    Treatment-emergent adverse events (AEs) up to 30 days after EOT.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
Official Title  ICMJE A Prospective, Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Effects of Macitentan on Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension Assessed by Cardiac Magnetic Resonance Imaging
Brief Summary The study evaluates the effect of macitentan on right ventricular and hemodynamic properties in patients with symptomatic pulmonary arterial hypertension. Patients are treated with macitentan for 1 year. Patients undergo right heart catheterization (RHC) at baseline and Week 26. They also undergo cardiac magnetic resonance imaging (MRI) at baseline, Week 26 and Week 52. Safety is monitored throughout the study. The study has three stub-studies. Each patient can participate in no sub-study or in one sub-study. The sub-studies are: (1) metabolism sub-study (with PET-MR scans); (2) biopsy sub-study (biopsies taken during the RHC); (3) Echo sub-study.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Drug: Macitentan
All patients take open-label macitentan 10mg o.d.
Other Name: ACT-064992
Study Arms  ICMJE Experimental: Macitentan
All patients take open-label macitentan 10mg o.d.
Intervention: Drug: Macitentan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 6, 2019)
89
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2014)
100
Actual Study Completion Date  ICMJE September 10, 2019
Actual Primary Completion Date September 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed informed consent prior to any study-mandated procedure
  2. Symptomatic pulmonary arterial hypertension (PAH)
  3. World Health Organization (WHO) Functional Class (FC) I to III
  4. PAH etiology belonging to one of the following groups according to Nice classification:

    • Idiopathic PAH
    • Heritable PAH
    • Drug- and toxin-induced PAH
    • PAH associated with congenital heart diseases: only simple (atrial septal defect, ventricular septal defect, patent ductus arteriosus) congenital systemic to pulmonary shunts at least 2 year post surgical repair
  5. Hemodynamic diagnosis of PAH confirmed by right heart catheterization (RHC) during screening showing:

    • mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and

    • PCWP (pulmonary capillary wedge pressure) or left ventricular end diastolic pressure (LVEDP) ≤ 12 mmHg and pulmonary vascular resistance (PVR) ≥ 4 Wood Units (WU) (320 dyn.sec.cm-5) or
    • 12 mmHg ≤ PCWP or LVEDP ≤ 15 mmHg and PVR ≥ 6WU (480 dyn.sec.cm-5)
  6. 6-minute walk distance (6MWD) ≥ 150 m during screening
  7. For patients treated with oral diuretics, treatment dose must have been stable at least 1 month prior to RHC during the screening period
  8. For patients treated with phosphodiesterase type-5 (PDE-5) inhibitors, treatment dose must have been stable at least 3 months prior to RHC during the screening period
  9. For patients treated with beta blockers, treatment dose must have been stable at least 1 month prior to the RHC during the screening period
  10. Men or women ≥18 and < 65 years
  11. Women of childbearing potential (defined in protocol) must:

    • Have a negative serum pregnancy test during screening and a negative urine pregnancy test on Day 1, and
    • Agree to use reliable methods of contraception (defined in protocol) from screening up to 30 days after study treatment discontinuation, and
    • Agree to perform monthly pregnancy tests up to 30 days after study treatment discontinuation

Exclusion Criteria:

  1. Body weight < 40 kg
  2. Body mass index (BMI) > 35kg/m2. For patients with 30kg/m2 < BMI < 35kg/m2, an eligibility form will be submitted to a Steering Committee member who will reserve the right to exclude the patient.
  3. Pregnancy, breastfeeding or intention to become pregnant during the study
  4. Recently started (< 8 weeks prior to informed consent signature) or planned cardio-pulmonary rehabilitation program
  5. Known concomitant life-threatening disease with a life expectancy < 12 months
  6. Any condition likely to affect protocol or treatment compliance
  7. Hospitalization for PAH within 3 months prior to informed consent signature
  8. Left atrial volume indexed for body surface area ≥ 43mL/m2 by echocardiography or cardiac MRI
  9. Valvular disease grade 2 or higher
  10. History of pulmonary embolism or deep vein thrombosis
  11. Documented moderate to severe chronic obstructive pulmonary disease
  12. Documented moderate to severe restrictive lung disease
  13. Historical evidence of significant coronary artery disease established by:

    • History of myocardial infarction or
    • More than 50% stenosis in a coronary artery (by percutaneous coronary intervention or angiography) or
    • Elevation of the ST segment on electrocardiogram or
    • History of coronary artery bypass grafting or
    • Stable angina
  14. Diabetes mellitus
  15. Moderate to severe renal insufficiency (calculated creatinine clearance < 60 mL/min/1.73 m2)
  16. Cancer
  17. Systolic blood pressure < 90 mmHg
  18. Severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by an aspartate aminotransferase (AST) elevation > ULN at Screening.
  19. Hemoglobin < 100g/L
  20. AST and/or alanine aminotransferase (ALT) > 3× ULN
  21. Need for dialysis
  22. Responders to acute vasoreactivity test based on medical history
  23. Prior use of endothelin receptor antagonists (ERAs), stimulators of soluble guanylate cyclase or prostacyclin or prostacyclin analogues
  24. Treatment with strong inducers of cytochrome P450 isozyme 3A4 (CYP3A4) within 4 weeks prior to study treatment initiation (e.g., carbamazepine, rifampicin, rifabutin, phenytoin and St. John's Wort)
  25. Treatment with strong inhibitors of CYP3A4 within 4 weeks prior to study treatment initiation (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)
  26. Treatment with another investigational drug (planned, or taken within the 3 months prior to study treatment initiation).
  27. Hypersensitivity to any ERA or any excipients of the formulation of macitentan (lactose, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, polyvinyl alcohol, polysorbate, titanium dioxide, talc, xanthan gum, and lecithin soya)
  28. Claustrophobia
  29. Permanent cardiac pacemaker, automatic internal cardioverter
  30. Metallic implant (e.g., defibrillator, neurostimulator, hearing aid, permanent use of infusion device)
  31. Atrial fibrillation, multiple premature ventricular or atrial contractions, or any other condition that would interfere with proper cardiac gating during MRI.
  32. For patients enrolling in the metabolism sub-study only: glucose intolerance
  33. For patients enrolling in the biopsy sub-study only: PAH etiology belonging to Nice classification 1.4.4: PAH associated with congenital heart diseases
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Hong Kong,   Israel,   Italy,   Malaysia,   Netherlands,   Russian Federation,   Singapore,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02310672
Other Study ID Numbers  ICMJE AC-055-403
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Loïc Perchenet Actelion
PRS Account Actelion
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP