Novartis Everolimus Transition

Safety and Efficacy of Everolimus Transition in Minimizing Progressive Graft Dysfunction and Interstitial Fibrosis in Adult Kidney Transplant Recipients

Transition from tacrolimus based triple therapy with Mycophenolate Mofetil (MMF) and steroids in stable renal transplant patients to low intensity tacrolimus, everolimus and prednisone will be associated with improvement in Glomular Filtration Rate (GFR) and allograft fibrosis.

Study Overview

• Status: Completed
• Conditions: Graft Dysfunction; Interstitial Fibrosis
• Intervention / Treatment: Drug: Everolimus; Other: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

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. At least 18 years of age and able to give informed consent.
2. Received a first or repeat cadaveric (including ECD) or living donor renal transplant.
3. Patient has stable graft function, defined as no change of greater than 40% of baseline serum creatinine and no acute rejection during the past month.
4. Currently receiving tacrolimus, mycophenolate mofetil and prednisone as their immunosuppression regimen

Exclusion Criteria:

1. Biopsy proven acute rejection episode that occurred within the past month.
2. Malignancy within the past 3 years, except for non-melanoma skin cancer.
3. Currently enrolled in an investigational drug trial.
4. Woman of child bearing potential not utilizing an effective form of birth control.
5. Patients with uncontrolled dyslipidemia, defined at serum fasting LDL >200 mg/dL or serum fasting triglycerides >500 mg/dL.
6. Patients with a spot urine protein to creatinine ratio of > 800 mg of protein per gram of creatinine.
7. WBC < 2,000 cells/mm3
8. Platelets < 75,000 cells/mm3
9. Patients who have received an organ transplant other than a kidney.
10. Patients with a history of biopsy proven FSGS, MPGN, or PGN.

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: Low intensity Tacrolimus; Low tacrolimus, everolimus, and steroids	Drug: Everolimus; Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus
Other: Standard of Care; Tacrolimus, mycophenolate mofetil and steroids	Other: Standard of Care; Tacrolimus, mycophenolate mofetil and steroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney Allograft Fibrosis Assessment	Measure and compare the change in interstitial fibrosis (morphometric analysis of trichrome stained slides) at one-year post-transplant in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen. The scale is a percentage of the tissue that demonstrates fibrosis. The scale range is 0 to 100%. The higher the percentage, the worse the fibrosis and the poorer the prognosis. A lower score (percentage) is therefore better.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR)	Measure and compare the estimated GFR (using the 4-variable modified MDRD equation) in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen, both at one year and two years post-transplant.	1 year
Kidney Allograft Survival	Compare the patient and graft survival rates at one-year post-transplant in each group.	1 year
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use	Measure and compare the rates of immunosuppressant discontinuation and modification for each group.	2 year
Adverse Drug Reactions	Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group.	2 year
Infection	Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group.	2 year

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Novartis
• Investigators: Principal Investigator: Titte Srinivas, MD, Medical University of South Carolina; Principal Investigator: David Taber, Medical University of South Carolina, Department of Surgery

Publications and helpful links

General Publications

• Taber DJ, Chokkalingam A, Su Z, Self S, Miller D, Srinivas T. Randomized controlled trial assessing the impact of everolimus and low-exposure tacrolimus on graft outcomes in kidney transplant recipients. Clin Transplant. 2019 Oct;33(10):e13679. doi: 10.1111/ctr.13679. Epub 2019 Sep 12.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 21, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: July 13, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Everolimus; Graft dysfunction; Interstitial fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Lung Diseases, Interstitial; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: Pro00030099