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Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD)

Primary Purpose

Acute Graft Versus Host Disease

Status
Terminated
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)
Sponsored by
Hadassah Medical Organization
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Graft Versus Host Disease focused on measuring acute graft versus host disease, intra arterial steroid infusion, steroid resistant acute hepatic graft versus host disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Recipient of allogeneic stem cell transplantation.
  • Age>18 years.
  • Post stem cells transplant <100 days.
  • AGVHD of liver, IBMTR index B, C, D.
  • Resistant AGVHD - Patients will be eligible for inclusion if they developed grade B-D AGVHD with progression after 3 days standard treatment OR unresponsive to at least 7 days standard treatment OR incomplete response to standard treatment after 14 days.
  • Has received no 1st line treatment for steroid refractory AGVHD.
  • Signed a written informed consent

Exclusion Criteria:

  • Not fulfilling any of the inclusion criteria.
  • Active life-threatening infection.
  • Inability to comply with study requirements.
  • Inability to give informed consent.
  • Contraindication to arterial catheterization (uncorrectable coagulopathy, severe allergic reaction to contrast material or others).
  • Inability to give the first Intra-arterial treatment in less than 72h from completion of inclusion criteria
  • An IBMTR index ≤ A.
  • Refractory skin AGVHD or severe diarrhea..
  • Pregnant or breast-feeding female or childbearing potential.
  • Known to be HIV positive.
  • Has been diagnosed with veno-occlusive disease.
  • Has been diagnosed with multi organ failure.
  • Known renal failure eGFR <30

Sites / Locations

  • Hadassah Medical Organisation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment

Arm Description

Outcomes

Primary Outcome Measures

Hepatic response
The degree to which serum bilirubin levels do or do not decrease

Secondary Outcome Measures

Full Information

First Posted
June 9, 2010
Last Updated
April 19, 2015
Sponsor
Hadassah Medical Organization
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1. Study Identification

Unique Protocol Identification Number
NCT01140984
Brief Title
Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD)
Official Title
An Investigator Initiated Open Study to Evaluate the Efficacy and Safety of Intra Arterial Infusion for Treatment of Steroid Resistant Acute Hepatic Graft Versus Host Disease (AGVHD)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Terminated
Why Stopped
technical issues
Study Start Date
September 2010 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hadassah Medical Organization

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Post allogeneic hematopoietic stem cell transplantation (HSCT) patients with steroid resistant acute GVHD localised to the liver will receive 24 hours continuous intra-arterial infusion of methylprednisolone.
Detailed Description
The study population will include 30 patients with SR AGVHD having an index of B, C, or D on the IBMTR severity index localized to the liver. Standard treatment for SR AGVHD includes: IV cyclosporine or tacrolimus with adjusted doses depending on serum levels and methylprednisolone or prednisone 2 mg/kg/d. This treatment may be continued during the study period although steroid taper down should be attempted if clinically possible. GVHD diagnosis will be based upon clinical criteria and biopsy (if needed) from an involved organ. GVHD will be graded according to the International Bone Marrow Transplantation Registry (IBMTR) severity index. Intra-arterial treatment should be given in less than 72h from completion of inclusion criteria. Partially responding or non-responding patients may receive a second treatment within 14 days of the initial intra-arterial treatment, at the discretion of the treating physician. Definitions Hepatic response: Initial response - the day in which bilirubin level began to decrease. Partial response 75 - the day in which bilirubin level decreased below 75% of basal level. Partial response 50 - the day in which bilirubin level decreased below 50% of basal level. Partial response 25 - the day in which bilirubin level decreased below 25% of basal level. Complete response - the day in which bilirubin level decreased to normal level.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Graft Versus Host Disease
Keywords
acute graft versus host disease, intra arterial steroid infusion, steroid resistant acute hepatic graft versus host disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)
Intervention Description
Sedation/anesthesia of patient followed by placement of a 4F vascular sheath and a diagnostic and hepatic angiogram. Angiographic catheter tip to be placed in the proximal proper hepatic artery, secured in place externally and connected to an arterial line pressurized system which allows continuous drip infusion of methylprednisolone diluted in normal saline (600mg/m2 with maximal total dose of 100mg diluted in 480cc in normal saline administered at 20cc/hr for 24 hours).
Primary Outcome Measure Information:
Title
Hepatic response
Description
The degree to which serum bilirubin levels do or do not decrease
Time Frame
180 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Recipient of allogeneic stem cell transplantation. Age>18 years. Post stem cells transplant <100 days. AGVHD of liver, IBMTR index B, C, D. Resistant AGVHD - Patients will be eligible for inclusion if they developed grade B-D AGVHD with progression after 3 days standard treatment OR unresponsive to at least 7 days standard treatment OR incomplete response to standard treatment after 14 days. Has received no 1st line treatment for steroid refractory AGVHD. Signed a written informed consent Exclusion Criteria: Not fulfilling any of the inclusion criteria. Active life-threatening infection. Inability to comply with study requirements. Inability to give informed consent. Contraindication to arterial catheterization (uncorrectable coagulopathy, severe allergic reaction to contrast material or others). Inability to give the first Intra-arterial treatment in less than 72h from completion of inclusion criteria An IBMTR index ≤ A. Refractory skin AGVHD or severe diarrhea.. Pregnant or breast-feeding female or childbearing potential. Known to be HIV positive. Has been diagnosed with veno-occlusive disease. Has been diagnosed with multi organ failure. Known renal failure eGFR <30
Facility Information:
Facility Name
Hadassah Medical Organisation
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel

12. IPD Sharing Statement

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Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD)

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