Status:
COMPLETED
REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
Lead Sponsor:
Actelion
Conditions:
Pulmonary Arterial Hypertension
Eligibility:
All Genders
18-64 years
Phase:
PHASE4
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 ye...
Eligibility Criteria
Inclusion
- Signed informed consent prior to any study-mandated procedure
- Symptomatic pulmonary arterial hypertension (PAH)
- World Health Organization (WHO) Functional Class (FC) I to III
- 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
- 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-minute walk distance (6MWD) ≥ 150 m during screening
- For patients treated with oral diuretics, treatment dose must have been stable at least 1 month prior to RHC during the screening period
- 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
- For patients treated with beta blockers, treatment dose must have been stable at least 1 month prior to the RHC during the screening period
- Men or women ≥18 and \< 65 years
- 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
- Body weight \< 40 kg
- 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.
- Pregnancy, breastfeeding or intention to become pregnant during the study
- Recently started (\< 8 weeks prior to informed consent signature) or planned cardio-pulmonary rehabilitation program
- Known concomitant life-threatening disease with a life expectancy \< 12 months
- Any condition likely to affect protocol or treatment compliance
- Hospitalization for PAH within 3 months prior to informed consent signature
- Left atrial volume indexed for body surface area ≥ 43mL/m2 by echocardiography or cardiac MRI
- Valvular disease grade 2 or higher
- History of pulmonary embolism or deep vein thrombosis
- Documented moderate to severe chronic obstructive pulmonary disease
- Documented moderate to severe restrictive lung disease
- 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
- Diabetes mellitus
- Moderate to severe renal insufficiency (calculated creatinine clearance \< 60 mL/min/1.73 m2)
- Cancer
- Systolic blood pressure \< 90 mmHg
- 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.
- Hemoglobin \< 100g/L
- AST and/or alanine aminotransferase (ALT) \> 3× ULN
- Need for dialysis
- Responders to acute vasoreactivity test based on medical history
- Prior use of endothelin receptor antagonists (ERAs), stimulators of soluble guanylate cyclase or prostacyclin or prostacyclin analogues
- 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)
- 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)
- Treatment with another investigational drug (planned, or taken within the 3 months prior to study treatment initiation).
- 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)
- Claustrophobia
- Permanent cardiac pacemaker, automatic internal cardioverter
- Metallic implant (e.g., defibrillator, neurostimulator, hearing aid, permanent use of infusion device)
- Atrial fibrillation, multiple premature ventricular or atrial contractions, or any other condition that would interfere with proper cardiac gating during MRI.
- For patients enrolling in the metabolism sub-study only: glucose intolerance
- For patients enrolling in the biopsy sub-study only: PAH etiology belonging to Nice classification 1.4.4: PAH associated with congenital heart diseases
Key Trial Info
Start Date :
June 1 2015
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 10 2019
Estimated Enrollment :
89 Patients enrolled
Trial Details
Trial ID
NCT02310672
Start Date
June 1 2015
End Date
September 10 2019
Last Update
March 30 2025
Active Locations (41)
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1
Massachussetts General Hospital
Boston, Massachusetts, United States, 02114
2
University of Minnesota
Minneapolis, Minnesota, United States, 55455
3
Washington University School of Medicine
St Louis, Missouri, United States, 63110
4
Rudgers New Jersey Medical School
New Brunswick, New Jersey, United States, 08901