NCT01265537

A Pilot Study Comparing the Use of Low-target Versus Conventional Target Advagraf

A Prospective, Open Label, Pilot Study Comparing the Use of Low-target Advagraf With Rabbit Antithymocyte Globulin Induction Versus Conventional Target Advagraf With Basiliximab Induction in a Steroid-avoidance Immunosuppressive Protocol for de Novo Renal Transplant Recipients

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University of British Columbia · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

While the incidence of acute rejection and early graft loss have improved dramatically with the advent of newer immunosuppressant medications, improvements in long-term patient and allograft survival after kidney transplantation have not been achieved. The specific drug combination that provides the best outcomes with the least amount of side effects is not known. Each kidney transplant center uses the combination of drugs that they believe is optimal. This study is about identifying whether drugs that are currently approved for use in kidney transplantation can be used in a new combination safely and with potentially fewer side effects than the drug combinations that are currently used at St. Paul's Hospital and other transplant centres.

Detailed description

Purpose This study has been designed to test whether using Thymoglobulin with low dose tacrolimus and early steroid withdrawal will minimize both kidney rejection and the development of new onset diabetes after transplant (NODAT). Justification Experimental treatment is low target tacrolimus with thymoglobulin. Standard treatment is a standard target (higher dose) tacrolimus and basiliximab, instead of thymoglobulin. The investigators hypothesize, that a combined approach of early steroid withdrawal and low dose tacrolimus in low immunologic risk transplant recipients will be effective in reducing the incidence of new onset diabetes mellitus, while maintaining a low risk of acute rejection. Objective The objective of this study is to compare early post-transplant outcomes with the use of low target versus standard target Advagraf in de novo kidney allograft recipients of low immunologic risk undergoing early corticosteroid withdrawal. Research Method This is a pilot study. Primary and secondary outcomes are as follows: Primary Outcome Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation. Secondary Outcomes * Patient survival * Graft survival * Frequency, severity, and treatment of hypertension * Frequency, severity, and treatment of hyperlipidemia (serum total cholesterol, (high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides) * Weight gain * Infections (cytomegalovirus (CMV), opportunistic infections including urinary tract infections requiring treatment, pneumonia) * Malignancy, including post-transplant lymphoproliferative disease (PTLD) * Leukopenia * Renal function as measured by serum creatinine and estimated Glomerular Filtration Rate (eGFR) The primary endpoint will be evaluated by time-to-event Kaplan Meier analysis and by Chi-squared analysis of final 6 month data. Statistical Analysis Sample size and power: In the setting of early steroid withdrawal, Woodle et al. reported an acute rejection rate of 14% with rATG and 24% with an interleukin-2 receptor antibody induction(10). The incidence of NODAT was reported at 21% by Woodle, et al., and was reported 10% in the low dose tacrolimus arm of the ELITE-Symphony trial. The investigators, therefore expect a combined event rate of 24% in Group A and 45% in group B. With a power of 0.80 and alpha error of 0.05, the investigators determined that the investigators need 72 subjects in each arm to demonstrate a 20% difference in our composite primary outcome. For this initial pilot study, the investigators aim to recruit a total of 30 subjects After receiving informed consent, subjects will be randomized on a 1:1 basis to one of the two treatment groups. Subjects who discontinue the study prematurely will not be replaced.

Conditions

• Acute Graft Rejection
• Diabetes

Interventions

Type	Name	Description
DRUG	Tacrolimus	Low target tacrolimus Advagraf (0.25mg/kg) orally once daily dosed as per manufacturer's recommendation to target trough levels as per Table 1 Table 1 Months post tx: 0-1 month, level 5-7; 1-3 months, level 4-5; and 3-6 months, level 3-4
DRUG	Tacrolimus	Standard dose of tacrolimus Advagraf (0.25mg/kg) orally once daily dosed as per manufacturer's recommendation to target trough levels as per Table 1 Table 1 Months post tx 0-1 month; level 8-12; 1-3 months, level 6-9; and 3-6 months, level 5-8.

Timeline

• Start date: 2011-06-24
• Primary completion: 2019-02-21
• Completion: 2019-10-11
• First posted: 2010-12-23
• Last updated: 2025-01-23
• Results posted: 2020-02-11

Locations

1 site across 1 country: Canada