Pulmonary arterial hypertension
Conditions
Interventions
6 mercaptopurin
pulmonary arterial hypertension
pulmonary vascular resistance
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 64 Years
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 * 3 months of at least oral monotherapy (PDE5-inhibitors, soluble guanyl cyclase stimulators, endothelin receptor antagonists or prostacyclin receptor agonist), patients in FC III received * 3 months of at least oral combination therapy, patients in FC IV received * 3 months 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, < 15% change in 6 minute walk distance (6MWD) - Right heart catheterization no longer than 4 weeks prior to enrollment showing precapillary pulmonary hypertension with mPAP * 25 mmHg (at rest), Pulmonary artery wedge pressure (PAWP) * 15 mmHg, PVR > 6 WU - Negative test results in regard to HIV, Hepatitis C/B, not older than 4 weeks - Able 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 - 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 - Thiopurine S-methyltransferase (TPMT) enzyme deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in pulmonary vascular resistance | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in cardiac function (right heart catheterization, MRI), exercise tolerance and quality of life. | — |
Countries
The Netherlands
Outcome results
None listed