Kidney Transplant Recipients
Conditions
Brief summary
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.
Interventions
DRUGmycophenolic acid
Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant.
Sponsors
Novartis Pharmaceuticals
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Acute Rejection by Banff '97 Criteria | Severity 1 year post transplant | 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. |
| Difference in Renal Function | Difference at 1 month, 3 months, 6 months, 1 year | 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. |
| Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97 | 1 year | 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. |
| Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Myfortic Preload Initiation of Myfortic 2 weeks prior to transplantation (with Simulect induction at time of transplant)
mycophenolic acid: Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant | 40 |
| Myfortic Standard Myfortic at time of transplant with Thymoglobulin induction
mycophenolic acid: Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant | 21 |
| Total | 61 |
Baseline characteristics
| Characteristic | Myfortic Preload | Total | Myfortic Standard |
|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 15 | 55.4 years STANDARD_DEVIATION 14 | 55.8 years STANDARD_DEVIATION 13.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 54 Participants | 19 Participants |
| Region of Enrollment United States | 40 participants | 61 participants | 21 participants |
| Sex: Female, Male Female | 12 Participants | 18 Participants | 6 Participants |
| Sex: Female, Male Male | 28 Participants | 43 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 40 | 8 / 21 |
| serious Total, serious adverse events | 19 / 40 | 10 / 21 |
Outcome results
Primary
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.
Time frame: 3, 6 and 12 months post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myfortic Preload | Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 3 months | 7 participants |
| Myfortic Preload | Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 6 months | 7 participants |
| Myfortic Preload | Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 12 months | 8 participants |
| Myfortic Standard | Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 3 months | 3 participants |
| Myfortic Standard | Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 6 months | 3 participants |
| Myfortic Standard | Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant | 12 months | 4 participants |
Secondary
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.
Time frame: Difference at 1 month, 3 months, 6 months, 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Myfortic Preload | Difference in Renal Function | 1 month | 1.41 mg/L | Standard Deviation 0.4 |
| Myfortic Preload | Difference in Renal Function | 3 months | 1.45 mg/L | Standard Deviation 0.5 |
| Myfortic Preload | Difference in Renal Function | 6 months | 1.43 mg/L | Standard Deviation 0.4 |
| Myfortic Preload | Difference in Renal Function | 1 year | 1.36 mg/L | Standard Deviation 0.4 |
| Myfortic Standard | Difference in Renal Function | 1 year | 1.5 mg/L | Standard Deviation 1 |
| Myfortic Standard | Difference in Renal Function | 1 month | 1.43 mg/L | Standard Deviation 0.6 |
| Myfortic Standard | Difference in Renal Function | 6 months | 1.40 mg/L | Standard Deviation 0.6 |
| Myfortic Standard | Difference in Renal Function | 3 months | 1.39 mg/L | Standard Deviation 0.5 |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myfortic Preload | Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97 | mild Chronic allograft nephropathy (CAN) | 9 participants |
| Myfortic Preload | Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97 | Moderate Chronic allograft nephropathy (CAN) | 0 participants |
| Myfortic Standard | Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97 | mild Chronic allograft nephropathy (CAN) | 3 participants |
| Myfortic Standard | Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97 | Moderate Chronic allograft nephropathy (CAN) | 1 participants |
Secondary
Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myfortic Preload | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Thymoglobulin | 6 participants |
| Myfortic Preload | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Intravenous immunoglobulin (IVIg) | 0 participants |
| Myfortic Preload | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Plasmapheresis | 0 participants |
| Myfortic Preload | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Rituximab | 0 participants |
| Myfortic Preload | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Pulse methylprednisolone | 5 participants |
| Myfortic Standard | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Rituximab | 1 participants |
| Myfortic Standard | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Pulse methylprednisolone | 3 participants |
| Myfortic Standard | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Thymoglobulin | 0 participants |
| Myfortic Standard | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Plasmapheresis | 2 participants |
| Myfortic Standard | Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection | Intravenous immunoglobulin (IVIg) | 0 participants |
Secondary
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.
Time frame: Severity 1 year post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myfortic Preload | Severity of Acute Rejection by Banff '97 Criteria | Grade IA | 3 participants |
| Myfortic Preload | Severity of Acute Rejection by Banff '97 Criteria | Grade IB | 4 participants |
| Myfortic Preload | Severity of Acute Rejection by Banff '97 Criteria | Grade IIA | 1 participants |
| Myfortic Preload | Severity of Acute Rejection by Banff '97 Criteria | Grade IIB | 0 participants |
| Myfortic Preload | Severity of Acute Rejection by Banff '97 Criteria | Antibody Mediated Rejection | 0 participants |
| Myfortic Preload | Severity of Acute Rejection by Banff '97 Criteria | Mixed Acute Rejection | 0 participants |
| Myfortic Standard | Severity of Acute Rejection by Banff '97 Criteria | Antibody Mediated Rejection | 1 participants |
| Myfortic Standard | Severity of Acute Rejection by Banff '97 Criteria | Grade IA | 1 participants |
| Myfortic Standard | Severity of Acute Rejection by Banff '97 Criteria | Grade IIB | 0 participants |
| Myfortic Standard | Severity of Acute Rejection by Banff '97 Criteria | Grade IB | 1 participants |
| Myfortic Standard | Severity of Acute Rejection by Banff '97 Criteria | Mixed Acute Rejection | 1 participants |
| Myfortic Standard | Severity of Acute Rejection by Banff '97 Criteria | Grade IIA | 0 participants |