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

A Prospective Randomized Trial of Prednisone and Tacrolimus Versus Prednisone, Tacrolimus and Mycophenolate Mofetil in Pediatric Liver Transplantation

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.

Study Overview

• Status: Terminated
• Conditions: Renal Insufficiency; Renal Failure; End-stage Liver Disease
• Intervention / Treatment: Other: placebo medication; Drug: mycophenolate mofetil

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: tacrolimus & corticosteroids; Standard post-transplant immunosuppression medications: tacrolimus and corticosteroids	Other: placebo medication; medication that looks like mycophenolate mofetil; Other Names: placebo pill
Experimental: low-dose tacrolimus + steroids + MMF; Comparison arm: low-dose tacrolimus + steroids + MMF	Drug: mycophenolate mofetil; immunosuppresion medication called mycophenolate mofetil, also known as MMF or CellCept; Other Names: CellCept; MMF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	two years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: John Goss, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: April 7, 2008
• First Submitted That Met QC Criteria: April 10, 2008
• First Posted (Estimate): April 11, 2008

Study Record Updates

• Last Update Posted (Actual): March 13, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: renal insufficiency or failure; liver transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Kidney Diseases; Urologic Diseases; Liver Diseases; End Stage Liver Disease; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: H-15138