A Study Looking at Diabetes in Kidney Transplant Recipients Receiving Immunosuppressive Regimen With or Without Steroids (ADVANCE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01304836
First received: February 3, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to focus on potential differences in the occurrence of new-onset Diabetes Mellitus (a glucose metabolism disorder) when two different regimens of immunosuppressive treatment are compared.


Condition Intervention Phase
Kidney Transplantation
Drug: Advagraf
Drug: Mycophenolate Mofetil
Drug: Simulect
Drug: Corticosteroids
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Investigating New Onset Diabetes Mellitus in Kidney Transplant Recipients Receiving an Advagraf-Based Immunosuppressive Regimen With or Without Corticosteroids - A Multicenter, Two Arm, Randomized, Open Label Clinical Study

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Diagnosis of new onset Diabetes Mellitus as per ADA criteria at any point up to 24 weeks after kidney transplantation [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy failure using a composite endpoint consisting of graft loss, biopsy confirmed acute rejection or graft dysfunction [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Positive Oral Glucose Tolerance Test [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Repeat Positive Oral Glucose Tolerance Test [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Renal function [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Acute Rejections [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Biopsy confirmed acute rejections [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Subject survival [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Graft survival [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Change from Baseline in HbA1C levels [ Time Frame: Baseline, week 12 and week 24 ] [ Designated as safety issue: No ]

Enrollment: 1166
Study Start Date: January 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 10 Days of Steroids
Advagraf + Basiliximab + MMF + Steroids (10 days)
Drug: Advagraf
oral
Other Names:
  • modified release tacrolimus
  • FK506E
Drug: Mycophenolate Mofetil
oral
Other Name: CellCept
Drug: Simulect
IV
Other Name: Basiliximab
Drug: Corticosteroids
IV & oral
Other Names:
  • methylprednisolone
  • prednisolone
Experimental: Optional Steroid bolus only
Advagraf + Basiliximab + MMF + Steroids (bolus only)
Drug: Advagraf
oral
Other Names:
  • modified release tacrolimus
  • FK506E
Drug: Mycophenolate Mofetil
oral
Other Name: CellCept
Drug: Simulect
IV
Other Name: Basiliximab
Drug: Corticosteroids
IV & oral
Other Names:
  • methylprednisolone
  • prednisolone

Detailed Description:

The primary objective of this study is to compare an Immunosuppressive regimen with 10 days of corticosteroids with a regimen with only an optional intra-op bolus of corticosteroids with regard to incidence of new onset Diabetes Mellitus as per the American Diabetic Association (ADA) criteria at any point up to 24 weeks after kidney transplantation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • End stage kidney disease and a suitable candidate for primary kidney transplantation or re-transplantation (unless the graft was lost from rejection within one year)
  • Receiving a kidney transplant from a deceased or living (non Human Leukocyte Antigen identical) donor with compatible AB0 blood type
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. A highly effective method of birth control is defined as those which result in a low failure rate (CPMP/ICH/286/95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner

Exclusion Criteria:

  • Receiving or having previously received an organ transplant other than a kidney
  • Cold ischemia time of the donor kidney > 30 hours
  • Panel Reactive Antibody >20% (Highest level in 6 months prior to transplant)
  • Previous renal transplant lost within one year for immunological reasons
  • Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest)
  • Significant liver disease, defined as having continuously elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor
  • Diagnosis of Diabetes Mellitus prior to transplantation (treated with prescribed medications or diet controlled) or where there is evidence of a previous positive Oral Glucose Tolerance Test (OGTT) in the patients medical history or previous diagnosis of gestational diabetes or pre-baseline HbA1C ≥6.5%
  • Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s).
  • Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (e.g. for Lupus Disease, FSGN etc) other than minimal levels of immunosuppressant following failure of a previous transplantation without nephrectomy
  • Where Physician considers long term steroid treatment is necessary for the prevention of recurrent auto immune mediated renal disease or if the subject requires ongoing dosing with corticosteroids during the study for any other condition
  • Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer
  • Pregnant woman or breast-feeding mother
  • Subject or donor known to be HIV positive
  • Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, basiliximab, mycophenolate mofetil or any of the product excipients
  • Evidence of malignant disease within the last 5 years other than Basal Cell Carcinoma or Squamous Cell Carcinoma
  • Currently participating in another clinical trial and/or has taken an investigational drug within 28 days prior to randomization
  • Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator
  • Unlikely to comply with the visits scheduled in the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01304836

  Show 100 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Use Central Contact Astellas Pharma Europe Ltd.
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01304836     History of Changes
Other Study ID Numbers: PMR-EC-1211, 2010-019638-28
Study First Received: February 3, 2011
Last Updated: July 17, 2014
Health Authority: Argentina: Ministry of Health
Australia: National Health and Medical Research Council
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Colombia: National Institutes of Health
Czech Republic: State Institute for Drug Control
Germany: Ministry of Health
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy
Italy: National Institute of Health
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Poland: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ministry of Health
Sweden: The National Board of Health and Welfare
Switzerland: Federal Office of Public Health
Turkey: Ministry of Health

Keywords provided by Astellas Pharma Inc:
Kidney
Transplant
Immunosuppression
Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Immunosuppressive Agents
Mycophenolate mofetil
Tacrolimus
Basiliximab
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents

ClinicalTrials.gov processed this record on August 28, 2014