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

NCT ID: NCT00656266

Last Updated: 2020-03-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30
• Study Completion Date: 2005-11-30

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.

Conditions

End-stage Liver Disease; Renal Insufficiency; Renal Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

tacrolimus & corticosteroids

Standard post-transplant immunosuppression medications: tacrolimus and corticosteroids

Group Type: PLACEBO_COMPARATOR

placebo medication

Intervention Type: OTHER

medication that looks like mycophenolate mofetil

low-dose tacrolimus + steroids + MMF

Comparison arm: low-dose tacrolimus + steroids + MMF

Group Type: EXPERIMENTAL

mycophenolate mofetil

Intervention Type: DRUG

immunosuppresion medication called mycophenolate mofetil, also known as MMF or CellCept

Interventions

mycophenolate mofetil

immunosuppresion medication called mycophenolate mofetil, also known as MMF or CellCept

Intervention Type: DRUG

placebo medication

medication that looks like mycophenolate mofetil

Intervention Type: OTHER

Other Intervention Names

CellCept; MMF; placebo pill

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.

• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

John Goss

Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Goss, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

H-15138

Identifier Type: -

Identifier Source: org_study_id