Treatment of Pulmonary Hypertension with 6 Mercaptopurine

Phase 1

• Conditions: Pulmonary arterial hypertension; MedDRA version: 20.0Level: HLGTClassification code 10037454Term: Pulmonary vascular disordersSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 20.0Level: HLTClassification code 10037401Term: Pulmonary hypertensionsSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

• Registration Number: EUCTR2017-000137-31-NL
• Lead Sponsor: VU University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-19
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• 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.
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

-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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Secondary end point(s): •A change in mean pulmonary artery pressure (mPAP)<br>•A change in cardiac output (CO)<br>•A change in right atrial pressure (RAP)<br>•A change in Functional Class<br>•Hospitalization for congestive heart failure (CHF)<br>•A change in VO2 max<br>•A change in 6 minute walking distance<br>•Change in NT-proBNP (pmol/L)<br>•A change in right ventricular ejection fraction (RVEF) (%)<br>•A change in right ventricular end diastolic volume (RVEDV) (ml)<br>•A change in right ventricular end systolic volume (RVESV) (ml)<br>•A change in EuroQol five dimensions questionnaire (EQ-5D)<br>•A change in Living with Pulmonary Hypertension questionnaire (LPH)<br>•A change in BORG dyspnea score;Timepoint(s) of evaluation of this end point: 4 months