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Novartis Everolimus Transition

Primary Purpose

Graft Dysfunction, Interstitial Fibrosis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Everolimus
Standard of Care
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Dysfunction focused on measuring Everolimus, Graft dysfunction, Interstitial fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

Low intensity Tacrolimus

Standard of Care

Arm Description

Low tacrolimus, everolimus, and steroids

Tacrolimus, mycophenolate mofetil and steroids

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Kidney Allograft Survival
Compare the patient and graft survival rates at one-year post-transplant in each group.
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use
Measure and compare the rates of immunosuppressant discontinuation and modification for each group.
Adverse Drug Reactions
Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group.
Infection
Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group.

Full Information

First Posted
February 28, 2014
Last Updated
July 13, 2018
Sponsor
Medical University of South Carolina
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT02096107
Brief Title
Novartis Everolimus Transition
Official Title
Safety and Efficacy of Everolimus Transition in Minimizing Progressive Graft Dysfunction and Interstitial Fibrosis in Adult Kidney Transplant Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
February 2014 (Actual)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
Collaborators
Novartis

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Dysfunction, Interstitial Fibrosis
Keywords
Everolimus, Graft dysfunction, Interstitial fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low intensity Tacrolimus
Arm Type
Active Comparator
Arm Description
Low tacrolimus, everolimus, and steroids
Arm Title
Standard of Care
Arm Type
Other
Arm Description
Tacrolimus, mycophenolate mofetil and steroids
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Tacrolimus, mycophenolate mofetil and steroids
Primary Outcome Measure Information:
Title
Kidney Allograft Fibrosis Assessment
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR)
Description
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.
Time Frame
1 year
Title
Kidney Allograft Survival
Description
Compare the patient and graft survival rates at one-year post-transplant in each group.
Time Frame
1 year
Title
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use
Description
Measure and compare the rates of immunosuppressant discontinuation and modification for each group.
Time Frame
2 year
Title
Adverse Drug Reactions
Description
Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group.
Time Frame
2 year
Title
Infection
Description
Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group.
Time Frame
2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: At least 18 years of age and able to give informed consent. Received a first or repeat cadaveric (including ECD) or living donor renal transplant. 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. Currently receiving tacrolimus, mycophenolate mofetil and prednisone as their immunosuppression regimen Exclusion Criteria: Biopsy proven acute rejection episode that occurred within the past month. Malignancy within the past 3 years, except for non-melanoma skin cancer. Currently enrolled in an investigational drug trial. Woman of child bearing potential not utilizing an effective form of birth control. Patients with uncontrolled dyslipidemia, defined at serum fasting LDL >200 mg/dL or serum fasting triglycerides >500 mg/dL. Patients with a spot urine protein to creatinine ratio of > 800 mg of protein per gram of creatinine. WBC < 2,000 cells/mm3 Platelets < 75,000 cells/mm3 Patients who have received an organ transplant other than a kidney. Patients with a history of biopsy proven FSGS, MPGN, or PGN.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Titte Srinivas, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Taber
Organizational Affiliation
Medical University of South Carolina, Department of Surgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31365151
Citation
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.
Results Reference
derived

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Novartis Everolimus Transition

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