Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity

NCT01473732 | Terminated Results DMC

• 1 other identifier: 11-05-196
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Allograft Injury; Calcineurin Inhibitor Toxicity

Keywords

CNI toxicity; CAI

Outcome Measures

Primary Outcomes (1)

• Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test

  Estimated glomerular filtration rate (eGFR) indicates kidney function. Normal eGFR value for healthy is 80-120ml/min. For transplants, it is expected to be 60-80 ml/min.

  Baseline, One year

Study Arms (2)

Everolimus (Zortress)

EXPERIMENTAL

Drug: Everolimus; Drug: Mycophenolic acid

Reduced dose Tacrolimus (Prograf)

ACTIVE COMPARATOR

Drug: Tacrolimus; Drug: Mycophenolic acid

Interventions

Everolimus DRUG

Starting dose 1.5 mg bid, target trough level 6-10 ng/ml.

Also known as: Zortress

Everolimus (Zortress)

Tacrolimus DRUG

Target trough level of Tacrolimus 3-5 ng/ml.

Also known as: Prograf

Reduced dose Tacrolimus (Prograf)

Mycophenolic acid DRUG

Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Used in both arms. Used for one year.

Also known as: Myfortic

Everolimus (Zortress); Reduced dose Tacrolimus (Prograf)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with biopsy proven pure chronic allograft injury due to CNI toxicity.

You may not qualify if:

• hour urine protein or spot urine protein/creatinine ratio \> 500 mg/day
• Estimated glomerular filtration rate (eGFR) \< 30 ml/min by modification of Diet in Renal Disease( MDRD) or 24 hour urine collection
• Patients with Donor-specific antibody (DSA) by Luminex (mean fluorescence intensity values \> 1,000)
• Recipients of multiple organ transplants or ABO-incompatible allograft
• Current panel reactive antibody (PRA) greater than 30 percent
• Graft loss at randomization
• Pregnant women
• Previous history of acute rejection
• Previous history of allergy or intolerance to Zortress or Myfortic
• Platelet count less than 100,000
• White Blood Cell (WBC) less than 3,000
• Hb less than 9 g/dL or Htc less than 30%
• Biopsy findings of
• Chronic antibody mediated rejection
• Acute rejection

Sponsors & Collaborators

• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

MeSH Terms

Interventions

Everolimus; Tacrolimus; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Enver Akalin, Medical Director Kidney Transplant
• Organization: Montefiore Medical Center

eakalin@montefiore.org

718-920-4815

Study Officials

• Enver Akalin, MD

  Montefiore Medical Center/AECOM

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dept of Medicine (Nephrology)

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 17, 2011
• Study Start: March 1, 2012
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 16, 2018
• Results First Posted: September 18, 2018

Record last verified: 2018-09

Locations

US (1)