Kidney Allograft Dysfunction Without Reversible Causes (KADWORC)

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: NCT01492894
Recruitment Status : Withdrawn (study terminated due to low enrollment)
First Posted : December 15, 2011
Last Update Posted : December 9, 2016
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Brief Summary:
The purpose of this study is to learn the best way to prolong kidney life in patients exposed to calcineurin inhibitors, who already have evidence of damage possibly caused by the calcineurin inhibitor on kidney biopsy.

Condition or disease Intervention/treatment Phase
Kidney Graft Dysfunction Drug: Cyclosporins/Tacrolimus Drug: Sirolimus Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Reducing Calcineruin Inhibitor Target Level by 50% Versus Converting to Rapamycin in Chronic Kidney Dysfunction Without Reversible Causes
Study Start Date : January 2008
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 50% decrease in calcineurin inhibitor Drug: Cyclosporins/Tacrolimus
Decrease the dose of calcineurin inhibitor by 1/2 and the drug level will be followed and adjusted to the target level of 50% of the previous levels
Other Names:
  • Gengraf (cyclosporin)
  • Neoral (cyclosporin)
  • Prograf (tacrolimus)

Active Comparator: Rapamune Drug: Sirolimus
Change from current calcineurin inhibitor to Sirolumus
Other Name: Rapamune

Primary Outcome Measures :
  1. Kidney function will be determined by the rate of change in glomerular filtration rate (GFR), estimated by serum creatinine (eGFR). [ Time Frame: Once a week for 3 month then monthly until trial ends ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Serum creatinine increased greater than or equal to 25% over baseline with no acute or reversible cause clinically evident.

    Although eGFR is arguably better for estimating kidney allograft function than serum creatinine, pragmatics dictate the use of a change in serum creatinine in the initial selection of patients. These criteria are currently used by transplant coordinators for selection of patients for the kidney biopsy as a part of large on-going study at our center.

  2. Adequate (greater than or equal to 8 glomeruli) biopsy showing Chronic allograft injury reported as mild/moderate CAN or CNI toxicity based on the previously used Banff 97 classification and no potentially reversible causes of graft dysfunction, e.g. acute rejection or treatable recurrent disease. Patients with histological evidence of mild recurrent disease that does not appear to be severe enough to explain the deterioration in function, e.g. IgA on immunofluorescence, or changes consistent with early diabetic nephropathy, will not be excluded.
  3. Receiving CsA (trough level concentration 75-125 ng/mL) or Tacrolimus(trough level concentration 6-12 ng/mL) plus MMF (or AZA) with (or without) prednisone.
  4. Able to give informed consent.

Exclusion Criteria:

  1. Urine total protein excretion >500 mg/g creatinine.
  2. eGFR (estimated by MDRD) <40 mL/min/1.73 m2
  3. Triglycerides >400 mg/dL or total cholesterol >300 mg/dL
  4. Allergy to macrolide antibiotic or rapamycin
  5. Women of child-bearing potential not using effective contraception
  6. Treated for acute rejection within the past 2 months
  7. <12 months after transplantation
  8. Potentially treatable cause(s) of allograft dysfunction, including acute rejection, dehydration, and congestive heart failure.
  9. Recurrent or de novo kidney disease that is histologically severe enough to be causing graft dysfunction
  10. Polyoma virus (BK) nephropathy, or serum positive for BK by polymerase chain reaction
  11. A second, functioning organ transplant.
  12. Receiving sirolimus.
  13. Patients with any past or present malignancy (other than non-melanoma skin cancer)

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): NCT01492894

United States, Minnesota
University of Minnesota Departments of Medicine and Surgery
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Aleksandra Kukula, MD University of Minnesota - Clinical and Translational Science Institute

Responsible Party: University of Minnesota - Clinical and Translational Science Institute Identifier: NCT01492894     History of Changes
Other Study ID Numbers: 0708M13942
First Posted: December 15, 2011    Key Record Dates
Last Update Posted: December 9, 2016
Last Verified: December 2016

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