Pulmonary arterial hypertension
Conditions
Interventions
4 months 6-MP treatment, in a dose of 1.5mg/kg (up to 150mg) once daily.
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Inclusion criteria
Inclusion criteria: - Age > 18 years - Diagnosis of idiopathic, hereditary or drug-induced PAH - New York Heart Association functional class (FC) II, III or IV - Prior to their screening right heart catheterization, patients in FC II received ¡Ý 30 days of at least oral monotherapy (PDE5-inhibitors, soluble guanyl cyclase stimulators, endothelin receptor antagonists or prostacyclin receptor agonist), patients in FC III received ¡Ý 30 days of at least oral combination therapy, patients in FC IV received ¡Ý 30 days triple therapy including a parenteral prostacyclin, unless intolerant for these medications - Stable on mono- or any combination therapy for at least 30 days prior to enrollment, as evidenced by stable drug doses (PAH medications and diuretics), no change in FC, 6 WU - Negative test results in regard to HIV, Hepatitis C/B, not older than 4 weeks - Thiopurine S-methyltransferase genotyping and activity (TPMT) is tested via peripheral blood testingAble to understand and willing to sign the Informed Consent Form. - PAH following one year repair of congenital heart defect (atrial septal defect, ventricle septal defect or persistent ductus arteriosus)PAH responsive to calcium antagonsists.
Exclusion criteria
Exclusion criteria: - PAH of any cause other than permitted in the entry criteria - Contraindication for right heart catheterization or CMR imaging - Any subject who had received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study - Known intolerance to 6-MP or TPMT enzyme deficiency - Active liver disease, porphyria or elevations of serums transaminases >3 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN - History or suspicion of inability to cooperate adequately. - Cancer or other malignant haematological disease - eGFR <30 ml/min - White blood count < 4.0 109/l - Hemoglobin < 6.0 mmol/l - Thrombocytes < 100 109/l - Transfer capacity for carbon monoxide (TLCO) < 40% of predicted - Total lung capacity (TLC) < 60% of predicted - Use of xanthineoxidase inhibitors - Pregnant female subjects - Breastfeeding female subjects - Female subjects unwilling or unable to use a highly effective method of contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study is the change in PVR, measured by right heart catheterization. | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary endpoints of this study are: Hemodynamically: • A change in mean pulmonary artery pressure (mPAP) • A change in cardiac output (CO) • A change in right atrial pressure (RAP) Clinical: • A change in FC • Hospitalization for congestive heart failure (CHF) • A change in VO2 max • A change in 6 minute walking distance Laboratory: • NT-proBNP (pmol/L) • Whole blood count • Kidney function • Liver tests • Platelet transcriptome Cardiovascular magnetic resonance imaging (CMR): • A change in right ventricular ejection fraction (RVEF) (%) • A change in right ventricular end diastolic volume (RVEDV) (ml) • A change in right ventricular end systolic volume (RVESV) (ml) Questionnaires: • A change in Living with Pulmonary Hypertension questionnaire (LPH) • A change in BORG dyspnea score | — |
Contacts
Public ContactL Botros
Outcome results
None listed