Treatment of Pulmonary Hypertension with 6 Mercaptopurine

• Register: EUCTR
• Last refreshed on: 3 November 2020
• Main ID: EUCTR2017-000137-31-NL
• Date of registration: 19/07/2017
• Prospective Registration: Yes
• Primary sponsor: VU University Medical Center
• Public title: Treatment of Pulmonary Hypertension with 6 Mercaptopurine
• Scientific title: Pulmonary Hypertension REversal in Clusters of Patients With Identical Pathobiological Substrates. 6-Mercaptopurine Proof-of-Concept Trial - PRECISE-MP
• Date of first enrolment: 19/12/2017
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000137-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Assoc. Prof. of Pulmonary Medicine
• Affiliation: VU University Medical Center

• Name: Assoc. Prof. of Pulmonary Medicine
• Affiliation: VU University Medical Center

Key inclusion & exclusion 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.
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

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

Intervention(s)

Trade Name: Puri-Nethol
Pharmaceutical Form: Tablet

Primary Outcome(s)

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

Main Objective: To obtain pilot safety and efficacy data on treatment of patients with pulmonary arterial hypertension (PAH) by 6-Mercaptopurine (6-MP)

Timepoint(s) of evaluation of this end point: 4 months

Primary end point(s): Pulmonary Vascular Resistance

Secondary Outcome(s)

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

Secondary ID(s)

2017-2019

Source(s) of Monetary Support

Netherlands Heart Foundation

Ethics review

Status: Approved
Approval date: 23/05/2017
Contact: