Kidney Allograft Dysfunction Without Reversible Causes (KADWORC)

A Randomized Controlled Trial of Reducing Calcineruin Inhibitor Target Level by 50% Versus Converting to Rapamycin in Chronic Kidney Dysfunction Without Reversible Causes

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.

Study Overview

• Status: Withdrawn
• Conditions: Kidney Graft Dysfunction
• Intervention / Treatment: Drug: Cyclosporins/Tacrolimus; Drug: Sirolimus

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Departments of Medicine and Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Rapamune

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Aleksandra Kukula, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: August 9, 2010
• First Submitted That Met QC Criteria: December 13, 2011
• First Posted (Estimate): December 15, 2011

Study Record Updates

• Last Update Posted (Estimate): December 9, 2016
• Last Update Submitted That Met QC Criteria: December 8, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Sirolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 0708M13942