Kidney Allograft Dysfunction Without Reversible Causes

Kidney Graft Dysfunction Clinical Trial

— KADWORC  

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01492894
• Other study ID #: 0708M13942
• Status: Withdrawn
• Phase: Phase 4
• First received: August 9, 2010
• Last updated: December 8, 2016
• Start date: January 2008
• Est. completion date: October 2011

Study information

• Verified date: December 2016
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Graft Dysfunction

Intervention

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
• Sirolimus
Change from current calcineurin inhibitor to Sirolumus

Locations

Country	Name	City	State
United States	University of Minnesota Departments of Medicine and Surgery	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes