Phase 4
N=87
REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
Pulmonary Arterial Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT02310672 ↗Enrolled (actual)
87
Serious AEs
17.2%
Results posted
Sep 2020
Primary outcome: Primary: Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26 — 15.17 milliliters (mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Macitentan (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Actelion
- Primary completion
- Sep 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26 |
15.17 | — |
| PRIMARY Ratio of Week 26 to Baseline Pulmonary Vascular Resistance (PVR) |
0.63 | — |
| SECONDARY Change From Baseline in Right Ventricular End Diastolic Volume (RVEDV) to Week 26 |
-6.22 | — |
| SECONDARY Change From Baseline in Right Ventricular End Systolic Volume (RVESV) to Week 26 |
-16.39 | — |
| SECONDARY Change From Baseline in Right Ventricular Ejection Fraction (RVEF) to Week 26 (% Blood Volume) |
10.14 | — |
| SECONDARY Change From Baseline in Right Ventricle (RV) Mass to Week 26 |
-10.10 | — |
| SECONDARY Change From Baseline in Six-minutes Walk Distance (6MWD) to Week 26 |
38.85 | — |
| SECONDARY Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26 |
5; 1; 35; 46 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 35kg/m2. For patients with 30kg/m2 3 × upper limit of the normal range (ULN) accompanied by an aspartate aminotransferase (AST) elevation > ULN at Screening.
- Hemoglobin 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
Data sourced from ClinicalTrials.gov (NCT02310672). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.