Clinical trial NCT00336817: A Prospective Study on the Tolerability and Efficacy of the de Novo Use of Myfortic in Liver Transplant Recipients
Official title: A Prospective Study on the Tolerability and Efficacy of the de Novo Use of Myfortic in Liver Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Immunosuppression
Keywords: Liver transplantation
mycophenolate mofetil
gastrointestinal
adverse effects
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2006-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to compare the safety and efficacy of Myfortic with CellCept in liver transplant patients. Myfortic and CellCept are both immunosuppressive (anti-rejection) drugs. CellCept is commonly used after liver transplantation but gastrointestinal (GI) side effects are very common, sometimes necessitating in its discontinuation. Myfortic is a new drug similar to CellCept, except it is enteric-coated. Our hypothesis is that Myfortic has less GI side effects than CellCept and also has comparable effectiveness to CellCept.

Detailed description: This is a prospective, randomized, double-blinded, single center, safety and efficacy study comparing Myfortic with CellCept used after liver transplantation. Patients with biopsy-proven acute cellular rejection, renal insufficiency (i.e. acute or chronic renal failure requiring hemodialysis or patients with creatinine clearance \< 50 ml/min), or calcineurin inhibitor-induced neurotoxicity (defined as the presence of neurologic symptoms such as tremors, altered mental status, seizures, etc) will be randomized to start on either Myfortic (720 mg po bid) or CellCept (1 gm po bid). In those patients with calcineurin-induced neurotoxicity or nephrotoxicity, tacrolimus or cyclosporine doses will also be reduced to maintain serum trough levels of 4-8 mg/dl or 100-200 mg/dl, respectively.

Comparison: Thirty patients will be enrolled and randomized in this two-armed, double-blinded study- half of the patients will receive Myfortic and the other half, CellCept.

Eligibility criteria: Inclusion Criteria:

* ALL patients will be adult liver transplant recipients, males or females, 18-80 years of age.
* Patients must be 30 to 180 days (1 to 6 months) post-transplant to be eligible.
* Patients currently receiving tacrolimus or cyclosporine with or without corticosteroids as part of their immunosuppressive regimen.
* Patients with renal insufficiency (history of renal insufficiency or renal failure in the past, patients on hemodialysis, patients with a rising creatinine post-transplant).
* Patients with biopsy-proven acute cellular rejection (mild, moderate, or severe based on Rejection Activity Index (RAI) as graded by pathologists at UPMC) or repeated bouts of rejection (greater than 2 episodes within a 30 day period).
* Patients with tacrolimus- or cyclosporine-induced neurotoxicity.
* Females of childbearing potential must have a negative serum pregnancy test prior to the inclusion period.

Exclusion Criteria:

* Multi-organ transplant patients.
* HIV positive patients.
* Living-related liver transplant recipients
* Pregnant patients and nursing mothers.
* Patients with a history of extra-hepatic malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin.
* Patients with thrombocytopenia (\<50,000/mm3), with an absolute neutrophil count of \<1,000/mm3 and/or leukocytopenia (\<2,000/mm3), and/or hemoglobin \<7.0 g/dL prior to enrollment.
* Presence of clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus.
* Evidence of drug and/or alcohol abuse.
* Decisionally impaired subjects who are not medically or mentally capable of providing consent themselves

Primary outcomes:
measure: GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil
timeFrame: screening, 2, 6 and 12 weeks
measure: GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil (Abdominal Pain Subscale)
timeFrame: screening, 2, 6 and 12 weeks
measure: GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil (Reflux Subscale)
timeFrame: screening, 2, 6 and 12 weeks
measure: GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Indigestion Subscale)
timeFrame: screening, 2, 6 and 12 weeks
measure: GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Diarrhea Subscale)
timeFrame: screening, 2, 6 and 12 weeks
measure: GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Constipation Subscale)
timeFrame: screening, 2, 6 and 12 weeks
measure: Number of Participants With Bone Marrow Suppression
timeFrame: 12 weeks
measure: Incidence of Cytomegalovirus Infection or Disease During the Study Period
timeFrame: 12 weeks
Secondary outcomes:
measure: Drug Discontinuation Due to Side Effects
timeFrame: 12 weeks
measure: Number of Participants With Clinically Significant Decrease in Serum Creatinine From Baseline Through Week 12
timeFrame: 12 weeks
measure: Number of Participants With Neurotoxicity
timeFrame: 12 weeks
Other outcomes:
measure: Incidence of Graft Loss or Death During the Study Period
timeFrame: 12 weeks
measure: Incidence of Biopsy-proven Acute Cellular Rejection During the Study Period
timeFrame: 12 weeks
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Michael E de Vera, MD
role: PRINCIPAL_INVESTIGATOR
References: