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

NCT01265537 | Completed Results

• 1 other identifier: H10-03047
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Graft Rejection; Diabetes

Keywords

Transplant; Tacrolimus; Diabetes after transplant; Acute rejection prevention; New onset diabetes after transplant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection

  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).

  6 months post transplant

Secondary Outcomes (11)

• Number of Participant Deaths

  6 months post transplant

• Number of Participants With Graft Failure

  6 months post transplant

• Number of Participants With Dialysis Events

  6 months post transplant

• Number of Participants With Infection Events

  6 months post transplant

• Number of Participants With Hospitalization Events

  6 months post transplant

Study Arms (2)

Low target tacrolimus (Advagraf)

EXPERIMENTAL

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

Standard target tacrolimus (Advagraf)

ACTIVE COMPARATOR

This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf.

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

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

Also known as: Advagraf

Low target tacrolimus (Advagraf)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients over 18 years of age who receive a deceased, living unrelated or living related donor renal transplant
• No history of pre-existing diabetes mellitus
• Not using diabetic medications (insulin, hypoglycemic agents) at the time of transplantation
• Random plasma glucose level \<11.1 at the time of transplantation
• Peak PRA (panel reactive antibody) \<30%
• 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
• The patient has given written informed consent to participate in the study

You may not qualify if:

• Patients with primary non-function
• Peak PRA\>=30%
• Multiple organ transplants
• HLA (human leukocyte antigen) identical living donor transplant recipients
• Cold ischemia time over 36 hours
• Nonheart beating donor kidney recipients
• Pediatric donor kidney recipients
• Donor age\>=65 years
• 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.
• Patients who are Epstein-Barr virus (EBV) negative and are receiving a transplant from an EBV-positive donor (mismatch).
• 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
• Patients with systemic infections
• Existence of any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, preclude enrollment in this trial
• Inability to cooperate or communicate with the investigator

Sponsors & Collaborators

• University of British Columbia: lead
• Astellas Pharma Canada, Inc.: collaborator

Study Sites (1)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Jagbir Gill
• Organization: St. Paul's Hospital

JAGill@providencehealth.bc.ca

6046822344

Study Officials

• Jagbir Gill, MD

  UBC / Dept of Medicine / Nephrology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 21, 2010
• First Posted: December 23, 2010
• Study Start: June 24, 2011
• Primary Completion: February 21, 2019
• Study Completion: October 11, 2019
• Last Updated: January 23, 2025
• Results First Posted: February 11, 2020

Record last verified: 2025-01

Locations

CA (1)