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. Identifier: NCT01265537
Recruitment Status : Unknown
Verified June 2016 by University of British Columbia.
Recruitment status was:  Recruiting
First Posted : December 23, 2010
Last Update Posted : June 29, 2016
Astellas Pharma Canada, Inc.
Information provided by (Responsible Party):
University of British Columbia

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 Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated 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
Study Start Date : March 2012
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

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 Name: 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 Name: Advagraf

Primary Outcome Measures :
  1. 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 oral glucose tolerance test(OGTT).

Secondary Outcome Measures :
  1. 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, DL, 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

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
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) <10%
  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>=10%
  3. Multiple organ transplants
  4. HLA (human leukocyte antigen) identical living donor transplant recipients
  5. Cold ischemia time over 24 hours
  6. Nonheart beating donor kidney recipients
  7. Pediatric donor kidney recipients
  8. Donor age>=60 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. 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
  11. Patients with systemic infections
  12. Existence of any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, preclude enrollment in this trial
  13. Inability to cooperate or communicate with the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01265537

Contact: Jesmint Dhillon, BSc 604-682-2344 ext 64708
Contact: Angela Ogniben, BA 604-682-2344 ext 64707

Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Jesmint Dhillon, BSc    604-862-2344 ext 64708   
Sponsors and Collaborators
University of British Columbia
Astellas Pharma Canada, Inc.
Principal Investigator: Jagbir Gill, MD UBC / Dept of Medicine / Nephrology

Responsible Party: University of British Columbia Identifier: NCT01265537     History of Changes
Other Study ID Numbers: H10-03047
First Posted: December 23, 2010    Key Record Dates
Last Update Posted: June 29, 2016
Last Verified: June 2016

Keywords provided by University of British Columbia:
Diabetes after transplant
Acute rejection prevention
New onset diabetes after transplant

Additional relevant MeSH terms:
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents