Pulmonary arterial hypertension MedDRA version: 20.0 Level: HLGT Classification code 10037454 Term: Pulmonary vascular disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level: HLT Classification code 10037401 Term: Pulmonary hypertensions System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Puri-Nethol
Pharmaceutical Form: Tablet
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
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, 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. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
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 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 |
|---|---|
| Main Objective: To obtain pilot safety and efficacy data on treatment of patients with pulmonary arterial hypertension (PAH) by 6-Mercaptopurine (6-MP);Secondary Objective: To determine whether platelet transcriptome analysis will identify a subset of PAH patients that responds to 6-MP treatment with hemodynamic and functional improvement;Primary end point(s): Pulmonary Vascular Resistance;Timepoint(s) of evaluation of this end point: 4 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • A change in mean pulmonary artery pressure (mPAP) • A change in cardiac output (CO) • A change in right atrial pressure (RAP) • A change in Functional Class • Hospitalization for congestive heart failure (CHF) • A change in VO2 max • A change in 6 minute walking distance • Change in NT-proBNP (pmol/L) • 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) • A change in EuroQol five dimensions questionnaire (EQ-5D) • A change in Living with Pulmonary Hypertension questionnaire (LPH) • A change in BORG dyspnea score;Timepoint(s) of evaluation of this end point: 4 months | — |
Countries
Netherlands
Contacts
Public ContactAssoc. Prof. of Pulmonary Medicine
VU University Medical Center
Outcome results
None listed