Pulmonary Hypertension REversal in Clusters of Patients With Identical Pathobiological Substrates. 6-Mercaptopurine Proof-of-Concept Trial

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 50

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

- 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