Overview

This trial is active, not recruiting.

Conditions chronic allograft injury, calcineurin inhibitor toxicity
Treatments everolimus, tacrolimus
Targets mTOR, FKBP-12
Sponsor Montefiore Medical Center
Start date November 2011
End date December 2013
Trial size 30 participants
Trial identifier NCT01473732, 11-05-196

Summary

The purpose of this study is to find out how well the current drug regimen (including low Prograf dose and Myfortic, which is usually recommended to prevent any further deterioration in the kidney function) works and how safe it is when compared to a combination of Zortress and Myfortic in patients with chronic kidney injury associated with Prograf or Neoral use.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
everolimus
Starting dose 1.5 mg bid, target trough level 6-10 ng/ml. Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Both for one year.
(Active Comparator)
tacrolimus
Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.

Primary Outcomes

Measure
EFFICACY AND SAFETY ASSESMENT
time frame: One year

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria: All patients with biopsy proven pure chronic allograft injury due to CNI toxicity. Exclusion Criteria: 1. 24 hour urine protein or spot urine protein/creatinine ratio > 500 mg/day 2. eGFR < 30 ml/min by MDRD or 24 hour urine collection 3. Patients with DSAs by Luminex (mean fluorescence intensity values > 1,000) 4. Recipients of multiple organ transplants or ABO-incompatible allograft 5. Current PRA greater than 30 percent 6. Graft loss at randomization 7. Pregnant women 8. Previous history of acute rejection 9. Previous history of allergy or intolerance to Zortress or Myfortic 10. Platelet count less than 100,000 11. WBC less than 3,000 12. Hb less than 9 g/dL or Htc less than 30% 13. Biopsy findings of - Chronic antibody mediated rejection - Acute rejection - Positive C4d staining - Interstitial infiltrates more than 25% of the area - Transplant glomerulopathy - Recurrent or de novo glomerular disease - Polyoma nephropathy or positive SV40 staining

Additional Information

Official title Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
Principal investigator Enver Akalin, MD
Description Specific Aim 1: To investigate allograft and peripheral blood cell gene expression patterns of patients with CAI by using Affymetrix microarrays. Hypothesis 1: Gene expression patterns of patients with biopsy findings suggesting calcineurin inhibitor (CNI) toxicity without significant tubulointerstitial infiltrates or transplant glomerulopathy might demonstrate upregulation of genes related to tissue injury, fibrosis, and extracellular matrix deposition without upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines comparing to patients with significant tubulointerstitial infiltrates and/or transplant glomerulopathy that might show upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines. Specific Aim 2: The effect of everolimus (Zortress)/ mycophenolate sodium (EC-MPS, myfortic®) treatment on allograft and peripheral gene expression patterns. Hypothesis 2: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) treatment attenuates the progression of CAI due to CNI toxicity by downregulating the expression of genes related to fibrosis, such as, transforming growth factor-β, thrombospondin 1, and platelet derived growth factor-C. Specific Aim 3: To document the clinical outcomes of everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) in patients with CAI due to CNI toxicity Hypothesis 3: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) can attenuate the progression of CAI due to CNI toxicity and may improve the creatinine clearance.
Trial information was received from ClinicalTrials.gov and was last updated in November 2011.
Information provided to ClinicalTrials.gov by Montefiore Medical Center.