Evaluate Effects and Safety of Pre-load Myfortic® in Transplant Patients

Study Overview
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Brief Summary
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This study is specifically designed to determine whether the initiation of Myfortic 2 weeks prior to transplantation will enhance the therapeutic efficacy of Simulect induction therapy in low to moderate risk patients. Specifically, the addition of Myfortic pretransplant to Simulect induction will be compared to standard Myfortic therapy with Thymoglobulin induction starting at the time of transplant in kidney transplant recipients.

Official Title
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A 12-month, Prospective, Randomized, Dual Center, Open Label Pilot Study to Evaluate the Safety and Efficacy of Myfortic® (Mycophenolic Acid) Loading Regimens in Combination With Thymoglobulin® [Anti-thymocyte Globulin (Rabbit)] or Simulect® (Basiliximab) Induction and Prograf® (Tacrolimus) in Early Corticosteroid Withdrawal

Conditions
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Kidney Transplant Recipients

Intervention / Treatment
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* Drug: mycophenolic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients capable of understanding the purposes and risks of the study. Patients who can give written informed consent, and who are willing and able to participate in the full course of the study. Women of childbearing potential must have a negative serum pregnancy test within the last 48 hours prior to receiving study medication. Women of childbearing potential must use two reliable forms of contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Effective contraception must be used before beginning study drug therapy, for the duration of the study and for 6 weeks following completion of the study. Exclusion Criteria: Patients who are recipients of a multiple organ transplant or if the patient previously received and organ transplant. Patients who are recipients of A-B-O incompatible transplants, all complement-dependent cytotoxicity (CDC) crossmatch positive transplants. Sensitized patients [most recent anti-Human Leukocyte Antigens (HLA) Class I panel reactive antibody (PRA) ≥ 25% by a CDC-based assay]. Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV). Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives. Patients with thrombocytopenia (<75,000/mm3 ), with an absolute neutrophil count of < 1,500/mm3); and/or leucopoenia (< 2,500/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion. Patient is taking or has been taking an investigational drug in the 30 days prior to transplant. Patient has a known hypersensitivity to tacrolimus, mycophenolate mofetil, enteric-coated mycophenolic acid, rabbit anti-thymocyte globulin, or corticosteroids. Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication; diabetic patients with previously diagnosed diabetic gastroenteropathy, or patients with active peptic ulcer disease. Patient is receiving chronic steroid therapy at the time of transplant. Patients with a history of malignancy within the last five years, except for successfully excised squamous or basal cell carcinoma of the skin. Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test. Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator. Inability to cooperate or communicate with the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Myfortic preload<br>Initiation of mycophenolic acid (Myfortic) 2 weeks prior to transplantation (with Simulect induction at time of transplant) | Drug: mycophenolic acid<br>* Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant.<br>* Other names: Myfortic;|
| Active Comparator: Myfortic standard<br>mycophenolic acid (Myfortic) at time of transplant with Thymoglobulin induction | Drug: mycophenolic acid<br>* Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant.<br>* Other names: Myfortic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | Incidence of biopsy-confirmed acute rejection by Banff '97 Criteria (updated 2007) post transplant. The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: As with humoral rejection, there are both acute & chronic forms: The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: Class IA: there is at least 25% of parenchymal showing interstitial infiltration and foci of moderate tubulitis (defined as a certain number of immune cells present in tubular cross-sections). Class IB: just like Class IA except there is more severe tubulitis. Class IIA: there is mild-to-moderate intimal arteritis. Class IIB: there is severe intimal arteritis comprising at least 25% of the lumenal area. Class III: there is transmural (e.g. the full vessel wall thickness) arteritis. | 3, 6 and 12 months post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Acute Rejection by Banff '97 Criteria | Severity of biopsy-confirmed acute rejection by Banff '97 Criteria (updated 2007) at 1 year. The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: As with humoral rejection, there are both acute & chronic forms: The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: Class IA: there is at least 25% of parenchymal showing interstitial infiltration and foci of moderate tubulitis (defined as a certain number of immune cells present in tubular cross-sections). Class IB: just like Class IA except there is more severe tubulitis. Class IIA: there is mild-to-moderate intimal arteritis. Class IIB: there is severe intimal arteritis comprising at least 25% of the lumenal area. Class III: there is transmural (e.g. the full vessel wall thickness) arteritis. | Severity 1 year post transplant | 
| Difference in Renal Function | Difference in renal function between groups at listed time points assessed by mean serum creatinine. Increased serum creatinine could indicate worsening renal function. A normal serum creatinine range for the transplant population varies by patient, but a typical range for Scr would be 1-2 mg/dL. | Difference at 1 month, 3 months, 6 months, 1 year | 
| Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97 | The Banff features suggestive of chronic rejection were: a) chronic transplant glomerulopathy: Glomerular basement membrane duplication and mesangial cell proliferation, and b) vasculopathy: Fibrous intimal thickening often with fragmentation of internal elastic lamina. Chronic changes in the interstitium (ci), tubules (ct), vessels (cv), and glomerulus (cg) were likewise graded into 0, 1, 2, and 3. The severity of interstitial fibrosis and tubular atrophy, as also chronic transplant glomerulopathy and vasculopathy were used to grade chronic allograft changes. | 1 year | 
| Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection |  | 1 year |