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

Phase 2

Brief Summary: 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: 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

1. 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

2. Patients (or one of parents if patients age \< 19) should sign informed consent.

Exclusion criteria

1. Patient with heart failure.

2. Patient with bleeding (intracranial hemorrhage, gastrointestinal tract bleeding, hemoptysis).

3. History of hypersensitivity reaction as shock to lipo-PGE1.

4. Psychiatric disorder that would preclude compliance.

5. If the clinician decides that there is a condition improper for the clinical study.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
lipoprostaglandin E1 treatment arm	lipoprostaglandin E1	* 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)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of VOD after transplantation	until 3 months after transplantation	cumulative incidence of VOD until 3 months after transplantation

Locations (1): Seoul National University Hospital
🇰🇷
Seoul, Chongno-gu, Korea, Republic of

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