Kidney Transplantation Clinical Trial
Official title:
A Phase III, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Prograf (Tacrolimus)/MMF, Modified Release (MR) Tacrolimus/MMF and Neoral (Cyclosporine)/MMF in de Novo Kidney Transplant Recipients
The purpose of this study is to compare the safety and efficacy of tacrolimus/mycophenolate mofetil (MMF), cyclosporine/MMF and tacrolimus modified release/MMF in de novo kidney transplant recipients.
Status | Completed |
Enrollment | 668 |
Est. completion date | March 2009 |
Est. primary completion date | March 2005 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 12 Years and older |
Eligibility |
Inclusion Criteria: - Recipient of a primary or retransplanted non-human leukocyte antigen (HLA)-identical living or non-HLA-identical cadaveric kidney transplant - Age greater or equal to 12 years Exclusion Criteria: - Recipient or donor is known seropositive for human immunodeficiency virus (HIV) - Has current malignancy or history of malignancy - Has significant liver disease - Has uncontrolled concomitant infection or any other unstable medical condition - Is receiving everolimus or enteric coated mycophenolic acid at any time during the study - Received kidney with a cold ischemia time of equal or more than 36 hours - Received kidney transplant from a cadaveric donor equal or more than 60 years of age - Received intravenous immunoglobulin (IVIG) therapy prior to randomization |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Astellas Pharma Inc |
United States, Brazil, Canada,
Silva HT Jr, Yang HC, Abouljoud M, Kuo PC, Wisemandle K, Bhattacharya P, Dhadda S, Holman J, Fitzsimmons W, First MR. One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients. Am J Transplant. 2007 Mar;7(3):595-608. Epub 2007 Jan 11. Erratum in: Am J Transplant. 2007 Jun;7(6):1682. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Participants With Efficacy Failure | Efficacy failure is defined as any participant who died, experienced a graft failure (permanent return to dialysis [> 30 days] or retransplant), had a biopsy-confirmed (Banff Grade = I) acute rejection (BCAR), or was lost to follow-up. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
one year | No |
Secondary | Patient Survival at One Year | Patient survival is defined as any participant who is known to be alive one year after the skin closure date. Participants who died or whose outcome was unknown at one year were considered to be non-survivors. | One year | No |
Secondary | Graft Survival at One Year | Graft survival defined as any participant who did not meet the criteria for graft loss, where graft loss is defined as any re-transplant, permanent return to dialysis (> 30 days), patient death, or participant whose outcome at one year was unknown. Participants were only counted once regardless of how many criteria were met. |
One year | No |
Secondary | Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months | Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. Acute rejection is defined as a grade = I. |
Six months and 12 months | No |
Secondary | Time to First Biopsy-confirmed Acute Rejection Episode | Time to first biopsy-confirmed acute rejection episode defined as the number of days from skin closure (Day 0) to the date of biopsy. Rejection episodes were confirmed by biopsy by the clinical site pathologist and graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. Acute rejection is defined as a grade = I. |
one year | No |
Secondary | Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection | Rejection episodes were confirmed by biopsy by the clinical site pathologist. Participants with histologically-proven Banff Grade II or III rejection or participants with steroid-resistant rejection were treated with anti-lymphocyte antibody treatment according to institutional practice. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
one year | No |
Secondary | Severity of Acute Rejection | Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade IA: Significant interstitial infiltration and foci of moderate tubulitis; Grade IB: Significant interstitial infiltration and foci of severe tubulitis; Grade IIA: Mild to moderate intimal arteritis in at least 1 arterial cross section Grade IIB: Severe intimal arteritis comprising >25% of the luminal area lost in at least 1 arterial cross section; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
one year | No |
Secondary | Number of Participants Experiencing Multiple Rejection Episodes | This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated. | one year | No |
Secondary | Number of Participants With Clinically Treated Acute Rejection Episodes | A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy. | one year | No |
Secondary | Number of Participants With Treatment Failure | Treatment failure was defined as the discontinuation of randomized study drug for any reason. Participants who met the definition of treatment failure were to be followed throughout the 12-month treatment period. | one year | No |
Secondary | Number of Participants Who Crossed Over Due to Treatment Failure | Participants were allowed to cross over to an alternative primary immunosuppressive regimen (either to the tacrolimus or cyclosporine treatment arms) to address an adverse event which led to randomized study drug discontinuation or in the case of severe or refractory rejection. Crossover to the modified release tacrolimus treatment arm was not permitted. | one year | No |
Secondary | Change From Month 1 in Serum Creatinine at Month 6 and Month 12 | Renal function was assessed by the change from Month 1 in serum creatinine six months and 12 months after transplant. | Month 1, Month 6, and Month 12 | No |
Secondary | Change From Month 1 in Creatinine Clearance at Month 6 and Month 12 | Renal function was assessed by creatinine clearance, calculated using the Cockcroft-Gault formula. | Month 1, Month 6, and Month 12 | No |
Secondary | Kaplan-Meier Estimate of Patient Survival at the End of the Study | Patient survival was defined as any participant who was alive at the end of the study. Patient survival was censored at the time of last follow-up contact. | End of study (maximum time on study was 1,941 days). | No |
Secondary | Kaplan-Meier Estimate of Graft Survival at the End of the Study | Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was any retransplant or the permanent return to dialysis (more than 30 days) or patient death. Graft survival was censored at the time of last follow-up contact. |
End of study (maximum time on study was 1,941 days). | No |
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