Comparing Everolimus and Sirolimus in Renal Transplant Recipients

A Prospective, Randomized, Single Center Pilot Study Comparing Patient and Graft Survival, Adverse Events and Tolerability of Zortress® (Everolimus) Versus Rapamune® (Sirolimus) in Combination With Low Dose Neoral® (Cyclosporine) Dosed by C2 Monitoring, in Deceased and Living Donor Renal Transplant Recipients Under a Thymoglobulin® (Antithymocyte Globulin) and Rapid Steroid Induction Protocol.

This study is being done to compare the effectiveness and safety of two different kidney transplant immunosuppression drugs, Zortress (the study drug) and Rapamune (which is used in the current standard immunosuppression regimen).

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: Everolimus; Drug: Sirolimus

Detailed Description

Zortress is FDA approved, is used as standard of care at some other institutions, and may also be given as standard of care if it is believed to be the best immunosuppression regimen for a particular kidney transplant recipient. The rationale for testing Zortress vs. Rapamune is to determine which of these drugs is more effective in preventing chronic rejection of the transplanted kidney. Because these two drugs are related to each other there is no current literature addressing the replacement of Rapamune with Zortress in an immunosuppression regimen, therefore the goal of this study is to compare these two immunosuppression drugs.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must give written informed consent before any assessment is performed.
2. Primary renal transplant recipients between ages 18 and 75 years of age.
3. Females capable of becoming pregnant must have a negative pregnancy test prior to transplantation and practice an effective form of birth control for the duration of the study and 12 weeks after discontinuation of the study drug if applicable.

Exclusion Criteria:

1. Total cholesterol > 300 mg/dl or triglycerides > 400 mg/dl despite lipid lowering therapy
2. Pre-existing bone marrow suppression (White Blood Cell count of < 3000, platelets < 100,000)
3. Active infection (Hepatitis B Virus, HIV)
4. Malignancy (except for adequately treated squamous or basal cell skin carcinoma) unless patient has written clearance from an Oncologist or if patient has had no malignancy for at least 2 years prior to the transplant
5. Allergy or intolerance to Zortress, Rapamune, cyclosporine, or Anti-thymocyte globulin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Zortress (Everolimus); Zortress will be started on day of transplant and initially dosed at 0.75 mg twice a day (12 hours apart) dosed simultaneously with Neoral.	Drug: Everolimus; 0.75mg twice a day, Orally, starting on day of transplant; Other Names: Zortress
ACTIVE_COMPARATOR: Rapamune (Sirolimus); Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d.	Drug: Sirolimus; 5mg, Orally, starting on day of transplant; decreasing to 3mg; Other Names: Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year	The primary objective of this pilot study will be to determine equivalency of Zortress® as compared to Rapamune® when used in our de novo immunosuppression regimen following renal transplantation. The primary endpoint will be a composite endpoint of graft survival (non-death censored) and biopsy proven acute rejection at 1 year. The primary outcome of immunosuppressive protection would be studied in our Thymoglobulin and rapid steroid discontinuation protocol, with "half-dose" Neoral as described above.	1 Year

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: Novartis
• Investigators: Principal Investigator: Amer Rajab, MD, OSU Wexner Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2013
• Primary Completion (ACTUAL): July 11, 2018
• Study Completion (ACTUAL): August 31, 2019

Study Registration Dates

• First Submitted: October 20, 2013
• First Submitted That Met QC Criteria: October 29, 2013
• First Posted (ESTIMATE): November 5, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Kidney; Renal failure; Kidney transplant; kidney transplant recipient
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Everolimus; Sirolimus
• Other Study ID Numbers: 2013H0229