Comparing Everolimus and Sirolimus in Renal Transplant Recipients

• Sponsor: Ohio State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01976390
• Collaborator: Novartis (Industry)
• Enrollment: 60
• Location: 1
• Arms: 2
• Actual Duration (Months): 71
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Renal Failure	Drug: Everolimus; Drug: Sirolimus	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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.
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jul 11, 2018
• Actual Study Completion Date: Aug 31, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Ohio State University
• Novartis

Investigators

• Principal Investigator: Amer Rajab, MD, OSU Wexner Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 16, 2013
• Informed Consent Form - Feb 10, 2012

More Information

Publications

None provided.

• Responsible Party: Ohio State University
• ClinicalTrials.gov Identifier: NCT01976390
• Other Study ID Numbers: 2013H0229
• First Posted: Nov 5, 2013
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Ohio State University: Kidney; Kidney transplant; Renal failure; End Stage Renal Disease; kidney transplant recipient
• Additional relevant MeSH terms: Renal Insufficiency; Sirolimus; Everolimus

Study Results

Participant Flow

Arm/Group Title	Zortress (Everolimus)	Rapamune (Sirolimus)
Arm/Group Description	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. Everolimus: 0.75mg twice a day, Orally, starting on day of transplant	Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d. Sirolimus: 5mg, Orally, starting on day of transplant; decreasing to 3mg
Period Title: Overall Study
STARTED	41	19
COMPLETED	41	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Zortress (Everolimus)	Rapamune (Sirolimus)	Total
Arm/Group Description	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. Everolimus: 0.75mg twice a day, Orally, starting on day of transplant	Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d. Sirolimus: 5mg, Orally, starting on day of transplant; decreasing to 3mg	Total of all reporting groups
Overall Participants	41	19	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.7 (11.9)	49.5 (12.2)	49.6 (11.9)
Sex: Female, Male (Count of Participants)
Female	17 41.5%	5 26.3%	22 36.7%
Male	24 58.5%	14 73.7%	38 63.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year
Description	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.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zortress (Everolimus)	Rapamune (Sirolimus)
Arm/Group Description	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. Everolimus: 0.75mg twice a day, Orally, starting on day of transplant	Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d. Sirolimus: 5mg, Orally, starting on day of transplant; decreasing to 3mg
Measure Participants	41	19
graft survival (non-death censored) at 1 year	40 97.6%	19 100%
biopsy proven acute rejection at 1 year	38 92.7%	19 100%

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Electronic medical records
Arm/Group Title	Zortress (Everolimus)		Rapamune (Sirolimus)
Arm/Group Description	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. Everolimus: 0.75mg twice a day, Orally, starting on day of transplant		Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d. Sirolimus: 5mg, Orally, starting on day of transplant; decreasing to 3mg
All Cause Mortality
	Zortress (Everolimus)		Rapamune (Sirolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/19 (0%)
Serious Adverse Events
	Zortress (Everolimus)		Rapamune (Sirolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/41 (85.4%)		17/19 (89.5%)
General disorders
Serious Adverse Effects	35/41 (85.4%)		17/19 (89.5%)
Other (Not Including Serious) Adverse Events
	Zortress (Everolimus)		Rapamune (Sirolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.