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Trial of Calcineurin Inhibitor-Sparing Immunosuppression Regimen in Pediatric Liver Transplantation

Primary Purpose

End-stage Liver Disease, Renal Insufficiency, Renal Failure

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
mycophenolate mofetil
placebo medication
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End-stage Liver Disease focused on measuring renal insufficiency or failure; liver transplantation

Eligibility Criteria

undefined - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • End-stage liver disease or acute fulminant hepatic failure recalcitrant to conventional medical or surgical therapy.
  • Listed as candidate for pediatric liver transplantation listed with United Network for Organ Sharing (UNOS).
  • Patients must be 18 years of age or younger.

Exclusion Criteria:

  • History of autoimmune disease or primary sclerosing cholangitis.
  • History of end-stage renal disease, dialysis treatment or acute renal failure (not including hepatorenal syndrome).
  • Patients with pretransplant renal insufficiency as determined by a glomerular filtration rate (GFR) of <80 mL/min/1.73m2 (see below).
  • Patients with renal agenesis or hypoplasia, polycystic kidney disease, or hydroureter seen on pretransplant renal ultrasound.
  • Patients with malignancy or previous malignancy.
  • Patients with active bacterial, viral, or fungal infections.
  • Patients with a pretransplant diagnosis of diabetes mellitus.
  • Patients with history of previous transplant or multi-organ recipients.
  • Patients with serological evidence of HIV, HBSAg or HCV.
  • Patients with hereditary syndrome that causes genetic deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan or Kelley-Seegmiller syndrome.
  • Patients with history of phenylketonuria.
  • Females that are pregnant or breastfeeding.
  • Sexually active females who are not: a) post-menopausal, or b) surgically sterile, and c) using an acceptable method of contraception (oral contraceptive, implanted devices, injection, and barrier devices are acceptable; condoms used alone are not acceptable).
  • Patients with alcohol abuse, substance abuse or smoking within the previous 6 months.
  • Patients or caretakers of patients with psychogenic factors that preclude therapeutic compliance.
  • Inability to reach participating hospital within 2 hours of notification.
  • Any conditions or any circumstance that makes it unsafe to undergo a liver transplant.

Sites / Locations

  • Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

tacrolimus & corticosteroids

low-dose tacrolimus + steroids + MMF

Arm Description

Standard post-transplant immunosuppression medications: tacrolimus and corticosteroids

Comparison arm: low-dose tacrolimus + steroids + MMF

Outcomes

Primary Outcome Measures

change in glomerular filtration rate (GFR) two years after liver transplantation as calculated by the Schwartz formula
change in glomerular filtration rate (GFR) two years after liver transplantation as calculated by the Schwartz formula

Secondary Outcome Measures

Full Information

First Posted
April 7, 2008
Last Updated
March 11, 2020
Sponsor
Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00656266
Brief Title
Trial of Calcineurin Inhibitor-Sparing Immunosuppression Regimen in Pediatric Liver Transplantation
Official Title
A Prospective Randomized Trial of Prednisone and Tacrolimus Versus Prednisone, Tacrolimus and Mycophenolate Mofetil in Pediatric Liver Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
insufficient funding
Study Start Date
November 2004 (undefined)
Primary Completion Date
November 2005 (Actual)
Study Completion Date
November 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this study is to compare the effects of two liver transplant immunosuppression regimens on renal function. Patients receiving the standard combination of prednisone and high-dose tacrolimus, a drug with known nephrotoxicity (Arm A) will be compared to patients receiving prednisone, low-dose tacrolimus and mycophenolate mofetil (MMF) (Arm B). MMF is an immunosuppression agent that has no associated nephrotoxicity. The primary end point of the study will be renal function as measured by glomerular filtration rate (GFR). Thirty pediatric liver transplant recipients will be randomized to these two arms in a 1:1 ratio (i.e. 15 patients in each group). Secondary end points will measure patient and graft outcome and incidence of immunosuppression-related complications, including: neurotoxicity, diabetes mellitus, growth retardation, vomiting, diarrhea, gastrointestinal hemorrhage, thrombocytopenia, anemia, leukopenia, acute or chronic liver graft rejection, posttransplant lymphoproliferative disease (PTLD), viral infections, fungal infections and bacterial infections.
Detailed Description
The objective of this study is to compare the effects of two liver transplant immunosuppression regimens on renal function. Patients receiving the standard combination of prednisone and high-dose tacrolimus, a drug with known nephrotoxicity (Arm A) will be compared to patients receiving prednisone, low-dose tacrolimus and mycophenolate mofetil (MMF) (Arm B). MMF is an immunosuppression agent that has no associated nephrotoxicity. The primary end point of the study will be renal function as measured by glomerular filtration rate (GFR). Thirty pediatric liver transplant recipients will be randomized to these two arms in a 1:1 ratio (i.e. 15 patients in each group). Secondary end points will measure patient and graft outcome and incidence of immunosuppression-related complications, including: neurotoxicity, diabetes mellitus, growth retardation, vomiting, diarrhea, gastrointestinal hemorrhage, thrombocytopenia, anemia, leukopenia, acute or chronic liver graft rejection, posttransplant lymphoproliferative disease (PTLD), viral infections, fungal infections and bacterial infections.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-stage Liver Disease, Renal Insufficiency, Renal Failure
Keywords
renal insufficiency or failure; liver transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tacrolimus & corticosteroids
Arm Type
Placebo Comparator
Arm Description
Standard post-transplant immunosuppression medications: tacrolimus and corticosteroids
Arm Title
low-dose tacrolimus + steroids + MMF
Arm Type
Experimental
Arm Description
Comparison arm: low-dose tacrolimus + steroids + MMF
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
CellCept, MMF
Intervention Description
immunosuppresion medication called mycophenolate mofetil, also known as MMF or CellCept
Intervention Type
Other
Intervention Name(s)
placebo medication
Other Intervention Name(s)
placebo pill
Intervention Description
medication that looks like mycophenolate mofetil
Primary Outcome Measure Information:
Title
change in glomerular filtration rate (GFR) two years after liver transplantation as calculated by the Schwartz formula
Description
change in glomerular filtration rate (GFR) two years after liver transplantation as calculated by the Schwartz formula
Time Frame
two years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: End-stage liver disease or acute fulminant hepatic failure recalcitrant to conventional medical or surgical therapy. Listed as candidate for pediatric liver transplantation listed with United Network for Organ Sharing (UNOS). Patients must be 18 years of age or younger. Exclusion Criteria: History of autoimmune disease or primary sclerosing cholangitis. History of end-stage renal disease, dialysis treatment or acute renal failure (not including hepatorenal syndrome). Patients with pretransplant renal insufficiency as determined by a glomerular filtration rate (GFR) of <80 mL/min/1.73m2 (see below). Patients with renal agenesis or hypoplasia, polycystic kidney disease, or hydroureter seen on pretransplant renal ultrasound. Patients with malignancy or previous malignancy. Patients with active bacterial, viral, or fungal infections. Patients with a pretransplant diagnosis of diabetes mellitus. Patients with history of previous transplant or multi-organ recipients. Patients with serological evidence of HIV, HBSAg or HCV. Patients with hereditary syndrome that causes genetic deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan or Kelley-Seegmiller syndrome. Patients with history of phenylketonuria. Females that are pregnant or breastfeeding. Sexually active females who are not: a) post-menopausal, or b) surgically sterile, and c) using an acceptable method of contraception (oral contraceptive, implanted devices, injection, and barrier devices are acceptable; condoms used alone are not acceptable). Patients with alcohol abuse, substance abuse or smoking within the previous 6 months. Patients or caretakers of patients with psychogenic factors that preclude therapeutic compliance. Inability to reach participating hospital within 2 hours of notification. Any conditions or any circumstance that makes it unsafe to undergo a liver transplant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Goss, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Trial of Calcineurin Inhibitor-Sparing Immunosuppression Regimen in Pediatric Liver Transplantation

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