Pharmacokinetic Study of Lipo-PGE1 for Prevention of VOD After HSCT

Study Overview
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Brief Summary
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Veno-occlusive disease (VOD) after hematopoietic stem cell transplantation (HSCT) remains the major complication. VOD occurs in 11-31% of pediatric HSCT and the mortality reaches up to 50%. Prostaglandin E1 (PGE1) have been reported to prevent and relieve the severity of VOD by Gluckman et al.. Lipo-PGE1 is a transporter of PGE1, which is superior in concentrating PGE1 and acts for prolonged time. Because of the prolonged effective time, lipo-PGE1 acts comparable effects by 1/4 1/8 of PGE1 dose. Empirically, pediatric HSCT centers adopt lipo-PGE1 in dose of 1 mcg/kg/day (0.042 mcg/kg/hr), which is 1/7 of the dose recommended by Gluckman, et al. This prospective study will investigate the concentration of lipo-PGE1 with preventive lipo-PGE1 with empirical dose (1 mcg/kg/day).

Detailed Description
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Primary Objective: To evaluate the pharmacokinetics of lipo-PGE1. Secondary objective: To evaluate the relation between lipo-PGE1 concentration and VOD occurrence, severity. Inclusion criteria Patients undergoing HSCT with high risk of VOD who cannot use low dose heparin. high risk of VOD : previous radiotherapy, liver function abnormality, children, conditioning regimen including busulfan or total body irradiation contraindication of heparin : low platelet count, bleeding tendency, allergy Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion criteria Patient with heart failure. Patient with bleeding (intracranial hemorrhage, gastrointestinal tract bleeding, hemoptysis). History of hypersensitivity reaction as shock to lipo-PGE1. Psychiatric disorder that would preclude compliance. If the clinician decides that there is a condition improper for the clinical study.

Official Title
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Pharmacokinetic Study of Lipo-PGE1 for Prevention of VOD After HSCT

Conditions
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Veno-occlusive Disease, Child

Intervention / Treatment
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* Drug: lipoprostaglandin E1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing HSCT with high risk of VOD who cannot use low dose heparin. high risk of VOD : previous radiotherapy, liver function abnormality, children, conditioning regimen including busulfan or total body irradiation contraindication of heparin : low platelet count, bleeding tendency, allergy Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion Criteria: Patient with heart failure. Patient with bleeding (intracranial hemorrhage, gastrointestinal tract bleeding, hemoptysis). History of hypersensitivity reaction as shock to lipo-PGE1. Psychiatric disorder that would preclude compliance. If the clinician decides that there is a condition improper for the clinical study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lipoprostaglandin E1 treatment arm<br>lipoprostaglandin E1 1mcg/kg/day, continuous infusion lipoprostaglandin E1 1.5mcg/kg/day, continuous infusion (for patients with elevating total bilirubin, hepatomegaly, right upper quadrant abdominal pain, unexplained weight gain) | Drug: lipoprostaglandin E1<br>* Blood sampling before administration (baseline), between 1 hour to 72 hours from administration (plateau 1), 72 hours after engraftment (plateau 2), when the clinician determine to do blood sampling because of change of kidney/liver function change (optional 1), 72 hours from the change of lipoprostaglandin E1 concentration change (optional 2)<br>* Other names: Alostin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics of lipo-PGE1 (Lipo-PGE1 level (B, P1, P2, O1, O2)) | Lipo-PGE1 drug level of time points (B, P1, P2, O1, O2) | baseline (pre-dose), 1 to 72 hours from starting continuous infusion of lipo-PGE1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of VOD after transplantation | cumulative incidence of VOD until 3 months after transplantation | until 3 months after transplantation |