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

• Sponsor: University of British Columbia (Other)
• Overall Status: Completed
• CT.gov ID: NCT01265537
• Collaborator: Astellas Pharma Canada, Inc. (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 99.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Graft Rejection; Diabetes	Drug: Tacrolimus; Drug: Tacrolimus	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jun 24, 2011
• Actual Primary Completion Date: Feb 21, 2019
• Actual Study Completion Date: Oct 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low target tacrolimus (Advagraf) This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf.	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; Other Names: Advagraf
Active Comparator: Standard target tacrolimus (Advagraf) This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf.	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.; Other Names: Advagraf

Outcome Measures

Primary Outcome Measures

1. Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection [6 months post transplant]

   Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation. NODAT will be defined as either FPG >7.0mmol/L OR symptoms of hyperglycemia and a random plasma glucose of >11.1 OR 2-h plasma glucose >11.1 during an oral glucose tolerance test(OGTT).

Secondary Outcome Measures

1. Number of Participant Deaths [6 months post transplant]

   Death of any participant by end of study.

2. Number of Participants With Graft Failure [6 months post transplant]

   Any graft failure by the end of the study.

3. Number of Participants With Dialysis Events [6 months post transplant]

   Any dialysis required by end of study.

4. Number of Participants With Infection Events [6 months post transplant]

   Any infection (CMV, opportunistic infections including urinary tract infections requiring treatment, pneumonia) by end of study.

5. Number of Participants With Hospitalization Events [6 months post transplant]

   Any hospitalization by end of study.

6. Number of Participants With Malignancy Events [6 months post transplant]

   Any malignancy (including post-transplant lymphoproliferative disease) by end of study.

7. Number of Participants With Cardiovascular Event [6 months post transplant]

   Any cardiovascular events by end of study.

8. Number of Any Leukopenia Events [6 months post transplant]

   Any leukopenia by end of study.

9. Number of Leukopenia Events on ≥2 Occasions [6 months post transplant]

   Any leukopenia on ≥2 occasions by end of study.

10. Change From Baseline in Weight [baseline to 6 months post transplant]

    Any changes in weight by end of study.

11. eGFR at 6 Months [6 months post transplant]

    Participant eGFR value by end of study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female patients over 18 years of age who receive a deceased, living unrelated or living related donor renal transplant

2. No history of pre-existing diabetes mellitus

3. Not using diabetic medications (insulin, hypoglycemic agents) at the time of transplantation

4. Random plasma glucose level <11.1 at the time of transplantation

5. Peak PRA (panel reactive antibody) <30%

6. Females capable of becoming pregnant must have a negative pregnancy test at baseline and are required to practice an approved method of birth control for the duration of the study and for a period of three months following discontinuation of study medication

7. The patient has given written informed consent to participate in the study

Exclusion Criteria:

1. Patients with primary non-function

2. Peak PRA>=30%

3. Multiple organ transplants

4. HLA (human leukocyte antigen) identical living donor transplant recipients

5. Cold ischemia time over 36 hours

6. Nonheart beating donor kidney recipients

7. Pediatric donor kidney recipients

8. Donor age>=65 years

9. Patients who are known to have a positive hepatitis C serology, who are human immunodeficiency virus (HIV) or Hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to study entry are acceptable. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C will be excluded.

10. Patients who are Epstein-Barr virus (EBV) negative and are receiving a transplant from an EBV-positive donor (mismatch).

11. Presence of any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or hypersensitivity to drugs similar to those used in the study

12. Patients with systemic infections

13. Existence of any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, preclude enrollment in this trial

14. Inability to cooperate or communicate with the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6

Sponsors and Collaborators

• University of British Columbia
• Astellas Pharma Canada, Inc.

Investigators

• Principal Investigator: Jagbir Gill, MD, UBC / Dept of Medicine / Nephrology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 3, 2017

More Information

Publications

None provided.

• Responsible Party: Jagbir Gill, Assistant Professor, University of British Columbia
• ClinicalTrials.gov Identifier: NCT01265537
• Other Study ID Numbers: H10-03047
• First Posted: Dec 23, 2010
• Last Update Posted: Feb 11, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Jagbir Gill, Assistant Professor, University of British Columbia: Transplant; Tacrolimus; Diabetes after transplant; Acute rejection prevention; New onset diabetes after transplant
• Additional relevant MeSH terms: Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Period Title: Overall Study
STARTED	15	15
COMPLETED	13	13
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)	Total
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.	Total of all reporting groups
Overall Participants	14	14	28
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	61.8	50.4	54.3
Sex: Female, Male (Count of Participants)
Female	4 28.6%	4 28.6%	8 28.6%
Male	10 71.4%	10 71.4%	20 71.4%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	4 28.6%	4 14.3%
Caucasian/White	13 92.9%	9 64.3%	22 78.6%
Other/Multiracial	1 7.1%	0 0%	1 3.6%
Pacific Islander	0 0%	1 7.1%	1 3.6%
Family History of Diabetes (participants) [Number]
Number [participants]	6 42.9%	6 42.9%	12 42.9%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.1 (3.0)	27.5 (6.3)	26.4 (5.1)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	150 (21)	159 (27)	154 (24)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	81 (9)	87 (9)	84 (9)
Cholesterol Medications (Count of Participants)
Yes	4 28.6%	2 14.3%	6 21.4%
No	10 71.4%	12 85.7%	22 78.6%
Cholestoral (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	4.56 (0.97)	4.43 (0.60)	4.49 (0.78)
Low-Density Lipoproteins (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	2.72 (0.82)	2.68 (0.76)	2.70 (0.77)
High-Density Lipoproteins (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	1.21 (0.28)	1.37 (0.62)	1.30 (0.49)
Triglycerides (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	1.38 (0.36)	1.52 (1.08)	1.46 (0.82)
Fasting Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.6 (0.8)	5.2 (0.6)	5.4 (0.7)
Random Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.5 (1.3)	5.7 (1.1)	5.6 (1.2)
Peak Panel-Reactive Antibody (PRA) before transplant (%) [Median (Full Range) ]
Median (Full Range) [%]	0	0	0
Donor Type (participants) [Number]
Living	11 78.6%	3 21.4%	14 50%
Deceased	3 21.4%	11 78.6%	14 50%
Donor Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	41	34	39
Human Leukocyte Antigen (HLA) Matches (Count of Participants)
0 matches	3 21.4%	6 42.9%	9 32.1%
1 match	4 28.6%	3 21.4%	7 25%
2 matches	3 21.4%	0 0%	3 10.7%
3 matches	1 7.1%	1 7.1%	2 7.1%
4 matches	1 7.1%	0 0%	1 3.6%
5 matches	1 7.1%	0 0%	1 3.6%
Missing	1 7.1%	4 28.6%	5 17.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection
Description	Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation. NODAT will be defined as either FPG >7.0mmol/L OR symptoms of hyperglycemia and a random plasma glucose of >11.1 OR 2-h plasma glucose >11.1 during an oral glucose tolerance test(OGTT).
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	2 14.3%	2 14.3%

2. Secondary Outcome

Title	Number of Participant Deaths
Description	Death of any participant by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With Graft Failure
Description	Any graft failure by the end of the study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants With Dialysis Events
Description	Any dialysis required by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	1 7.1%	3 21.4%

5. Secondary Outcome

Title	Number of Participants With Infection Events
Description	Any infection (CMV, opportunistic infections including urinary tract infections requiring treatment, pneumonia) by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	5 35.7%	5 35.7%

6. Secondary Outcome

Title	Number of Participants With Hospitalization Events
Description	Any hospitalization by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	0 0%	4 28.6%

7. Secondary Outcome

Title	Number of Participants With Malignancy Events
Description	Any malignancy (including post-transplant lymphoproliferative disease) by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	0 0%	1 7.1%

8. Secondary Outcome

Title	Number of Participants With Cardiovascular Event
Description	Any cardiovascular events by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Count of Participants [Participants]	0 0%	0 0%

9. Secondary Outcome

Title	Number of Any Leukopenia Events
Description	Any leukopenia by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Number [events]	11	3

10. Secondary Outcome

Title	Number of Leukopenia Events on ≥2 Occasions
Description	Any leukopenia on ≥2 occasions by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Number [events]	6	0

11. Secondary Outcome

Title	Change From Baseline in Weight
Description	Any changes in weight by end of study.
Time Frame	baseline to 6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Median (Inter-Quartile Range) [kg]	2.8	1.5

12. Secondary Outcome

Title	eGFR at 6 Months
Description	Participant eGFR value by end of study.
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

The discrepancy in the overall number of participants with outcome measure data and the overall number of participants in the participant flow module is seen because 28 participants in total have outcome measure data available.

Arm/Group Title	Low Target Tacrolimus (Advagraf)	Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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	This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
Measure Participants	14	14
Median (Inter-Quartile Range) [mL/min/1.73^2]	56	51

Adverse Events

Time Frame	Adverse event data was collected from the baseline visit until 6 months post transplant.
Arm/Group Title	Low Target Tacrolimus (Advagraf)		Standard Target Tacrolimus (Advagraf)
Arm/Group Description	This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. 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		This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. 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.
All Cause Mortality
	Low Target Tacrolimus (Advagraf)		Standard Target Tacrolimus (Advagraf)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Low Target Tacrolimus (Advagraf)		Standard Target Tacrolimus (Advagraf)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/14 (50%)		7/14 (50%)
Immune system disorders
Malignancy	1/14 (7.1%)		0/14 (0%)
Infections and infestations
Infections	5/14 (35.7%)		5/14 (35.7%)
Renal and urinary disorders
Dialysis	2/14 (14.3%)		2/14 (14.3%)
Acute Rejection	1/14 (7.1%)		2/14 (14.3%)
Other (Not Including Serious) Adverse Events
	Low Target Tacrolimus (Advagraf)		Standard Target Tacrolimus (Advagraf)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.