Systemic sclerosis-patients (SSc) with borderline pulmonary arterial hypertension
Conditions
Interventions
Trade Name: Volibris
Product Name: Ambrisentan
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the place
Sponsors
Thoraxklinik-Heidelberg gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female SSc patients with borderline - PAH and: 2. mPAP 21-24 mmHg, transpulmonary gradient >11 mmHg, as defined by the current ESC Guidelines, PAWP 30 mmHg, (PAWP 3 years 7. Able to understand and willing to sign the Informed Consent Form 8. Negative pregnancy test at the start of the trial and appropriate contraception throughout the study for women with child-bearing potential. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Any connective tissue diseases (CTD) other than SSc 2. Pulmonary hypertension (PH) confirmed by right heart catheter (RHC) before enrolment, i.e. mPAP =25 mmHg at rest 3. Patients presenting normal mPAP values, i.e. mPAP2 weeks of continued use of therapies that are considered definitive PH treatment: endothelin receptor antagonists (ERA; e.g. bosentan, ambrisentan), phosphodiesterase type 5 inhibitors (PDE5; e.g. sildenafil, tadalafil, vardenafil), and prostanoids (e.g. epoprostenol, treprostinil, iloprost, beraprost) and soluble guanylate cyclase stimulator (e.g. Riociguat). Intermittent use of PDE5 inhibitors for male erectile dysfunction is permitted. 5. Except for diuretics and corticosteroids medical treatment should not be expected to change 4 weeks prior inclusion into the study and during the entire 12-week study period. 6. Known intolerance to ambrisentan or one of its excipients 7. Clinically significant anemia (hemoglobin concentration of less than 75% of the lower limit of normal, LLN) 8. Forced vital capacity (FVC) 3 x upper limit of normal (ULN) 12. Systolic blood pressure 160/90 mmHg and/or blood pressure during exercise >220/120 mmHg 14. Patients referred with clinically significant overt heart failure 15. Clinically significant fluid retention 16. Previous evidence or diagnosis of clinically relevant left heart disease, i.e. at least one of the following: Previous echocardiography with estimated left ventricular (LV) ejection fraction 50 mm) 17. Known significant diastolic dysfunction associated with clinical heart failure 18. Known coronary disease or significant valvular heart disease 19. Known congenital heart defects such as single ventricle, transposition, Eisenmenger 20. Known hypertrophic cardiomyopathy or left ventricular hypertrophy (interventricular septum thickness (IVS) or posterior wall thickness (PWD) >1.2 cm) 21. Participation in any clinical drug trial within 4 weeks prior to screening of this study and/or who is scheduled to receive another investigational medicinal product (IMP) during the course of this study 22. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 2) Determine whether exercise induced elevated mPAP-values (>30 mmHg without left heart or severe lung disease or systemic arterial hypertension) and further measures of exercise capacity, symptoms and quality of life can be reduced by ambrisentan 10 mg/die over 6 months. 3) Analyze if the progression (adverse events, hospitalization, initiation of pulmonary hypertension treatment) of borderline-PAH to manifest PH can be avoided by ambrisentan-treatment (descriptive, observational). 4) Assessment of tolerability and safety;Primary end point(s): 1) Determine whether mPAP of SSc patients with borderline - PAH (mPAP 21 24 mmHg, TPG >11 mmHg) can be reduced by 3 mm Hg (absolute change baseline vs. 6 months; equals 15%) by treatment with ambrisentan 10 mg/die (initiated with 5 mg/die and elevated up to 10 mg/die) over 6 months (primary endpoint) compared to baseline and placebo;Main Objective: Determine whether mPAP of SSc patients with borderline - PAH (mPAP 21 24 mmHg, TPG >11 mmHg) can be reduced by 15% following treatment with ambrisentan 10 mg/die (initiated with 5 mg/die and elevated up to 10 mg/die) over 6 months compared to baseline and placebo.;Timepoint(s) of evaluation of this end point: At 6 months of treatment start with study medication | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Analyze if in patients with SSc and borderline-PAP show an improvement by treatment with ambrisentan 10 mg/die over 6 months in: - 6-Minute-walking test - Quality of life (SF-36) - Lung function tests (DLCo, DLCo/VA, FVC, FEV1, TLC, residual volume) - Echocardiography (RA-area, RV-area, Tei, TAPSE, sPAP) - Borg Dyspnea Index - WHO-functional class - further invasively measured hemodynamic parameters evaluated by RHC: right atrial pressure, pulmonary vascular resistance, cardiac output (CO), cardiac index (CI), PAWP, venous oxygen saturation (SvO2) - Raynaud-syndrome and skin involvement, assessed by the modified Rodnan-Skin score and Symptoms of Scleroderma (descriptive);Timepoint(s) of evaluation of this end point: At 6 months of treatment start with study medication | — |
Countries
Germany
Contacts
Public ContactDirector of the clinic
Thoraxklinik am Universitätsklinikum Heidelberg
Outcome results
None listed