Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01265537
Recruitment Status : Completed
First Posted : December 23, 2010
Results First Posted : February 11, 2020
Last Update Posted : February 11, 2020
Sponsor:
Collaborator:
Astellas Pharma Canada, Inc.
Information provided by (Responsible Party):
Jagbir Gill, University of British Columbia

Tracking Information
First Submitted Date  ICMJE December 21, 2010
First Posted Date  ICMJE December 23, 2010
Results First Submitted Date  ICMJE November 27, 2019
Results First Posted Date  ICMJE February 11, 2020
Last Update Posted Date February 11, 2020
Actual Study Start Date  ICMJE June 24, 2011
Actual Primary Completion Date February 21, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2020)
Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2010)
New onset diabetes after transplant (NODAT) [ Time Frame: 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 OGTT.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2020)
  • Number of Participant Deaths [ Time Frame: 6 months post transplant ]
    Death of any participant by end of study.
  • Number of Participants With Graft Failure [ Time Frame: 6 months post transplant ]
    Any graft failure by the end of the study.
  • Number of Participants With Dialysis Events [ Time Frame: 6 months post transplant ]
    Any dialysis required by end of study.
  • Number of Participants With Infection Events [ Time Frame: 6 months post transplant ]
    Any infection (CMV, opportunistic infections including urinary tract infections requiring treatment, pneumonia) by end of study.
  • Number of Participants With Hospitalization Events [ Time Frame: 6 months post transplant ]
    Any hospitalization by end of study.
  • Number of Participants With Malignancy Events [ Time Frame: 6 months post transplant ]
    Any malignancy (including post-transplant lymphoproliferative disease) by end of study.
  • Number of Participants With Cardiovascular Event [ Time Frame: 6 months post transplant ]
    Any cardiovascular events by end of study.
  • Number of Any Leukopenia Events [ Time Frame: 6 months post transplant ]
    Any leukopenia by end of study.
  • Number of Leukopenia Events on ≥2 Occasions [ Time Frame: 6 months post transplant ]
    Any leukopenia on ≥2 occasions by end of study.
  • Change From Baseline in Weight [ Time Frame: baseline to 6 months post transplant ]
    Any changes in weight by end of study.
  • eGFR at 6 Months [ Time Frame: 6 months post transplant ]
    Participant eGFR value by end of study.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2010)
Acute rejection [ Time Frame: 6 months post transplant ]
  • Patient survival
  • Graft survival
  • Frequency, severity, and treatment of hypertension
  • Frequency, severity, and treatment of hyperlipidemia (serum total cholesterol, HDL, LDL, and triglycerides)
  • Weight gain
  • Infections (CMV, opportunistic infections including urinary tract infections requiring treatment, pneumonia)
  • Malignancy, including PTLD
  • Leukopenia
  • Renal function as measured by serum creatinine and MDRD eGFR
  • Therapy with anti-diabetic medications beyond 1 month post transplant
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Study Comparing the Use of Low-target Versus Conventional Target Advagraf
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Graft Rejection
  • Diabetes
Intervention  ICMJE
  • 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 Name: 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 Name: Advagraf
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Tacrolimus
  • 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.
    Intervention: Drug: Tacrolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 22, 2010)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 11, 2019
Actual Primary Completion Date February 21, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01265537
Other Study ID Numbers  ICMJE H10-03047
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jagbir Gill, University of British Columbia
Study Sponsor  ICMJE University of British Columbia
Collaborators  ICMJE Astellas Pharma Canada, Inc.
Investigators  ICMJE
Principal Investigator: Jagbir Gill, MD UBC / Dept of Medicine / Nephrology
PRS Account University of British Columbia
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP