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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Child; Veno-occlusive Disease
• Intervention / Treatment: Drug: lipoprostaglandin E1

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chongno-gu
    • Seoul, Chongno-gu, Korea, Republic of
      • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lipoprostaglandin E1 treatment arm; 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; 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); Other Names: Alostin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Hyoung Jin Kang, MD, PhD, Seoul National University College of Medicine

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): December 1, 2019
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: December 30, 2014
• First Submitted That Met QC Criteria: January 11, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 28, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: SNUCH-HSCT-lipoPGE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided