Study in Recipients of Renal Transplant Allograft to Evaluate the Impact of Two Immunosuppressive Regimens

NCT01653847 | Completed Results

• 1 other identifier: Novartis- Everolimus
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The immune system is the body's defense against infection and other disease. After transplantation, the body sees the new organ as "foreign" and tries to destroy or "reject" it. Immunosuppressive medications help to prevent the immune system from attacking a transplanted organ. The primary purpose of this study is to investigate the impact of two maintenance immunosuppressive regimens. Subjects who enroll in this study will be randomly selected to have tacrolimus and everolimus (group 1) or tacrolimus and mycophenolate mofetil (group 2) as their immunosuppression medication. This study will enroll adult patients who are scheduled to receive a kidney transplant. The study is designed to understand the mechanisms of Everolimus in regards to kidney function in transplant recipients. The investigators hypothesis is that decreased exposure to Tacrolimus to the immune system will then translate in better renal allograft function.

Conditions

End Stage Renal Failure With Renal Transplant

Keywords

transplant; kidney; renal disease

Outcome Measures

Primary Outcomes (2)

• Change in T Cell & B Cell Generation

  Evaluate the change in regulatory T cell generation and review the relationship of the newly generated T cells with their function in the two maintenance immunosuppressive regimens at baseline, 3 and 12 months post-transplant.

  Baseline, 3 months, and 12 months post-transplant

• Change in Glomerular Filtration Rate (GFR)

  Evaluate the change in graft function (as measured by GFR) at 12 months post-transplant from baseline.

  3 months, 6 months, and 12 months post-transplant

Secondary Outcomes (3)

• Patient Survival

  baseline - 24 months post transplant

• Renal Allograft Survival

  12 months post-transplant

• Acute Rejection

  12 months post transplant

Study Arms (3)

Group 1: Tacrolimus with MMF.

ACTIVE COMPARATOR

This group will receive a standard dose Tacrolimus and MMF. This will follow standard of care protocol at Northwestern Memorial Hospital's Comprehensive Transplant Center.

Drug: Tacrolimus with MMF

Group 2: Tacrolimus with Everolimus

ACTIVE COMPARATOR

This group will receive a low dose Tacrolimus with concentration controlled Everolimus

Drug: Group 2: Tacrolimus with Everolimus.

Donors

NO INTERVENTION

One time blood samples will be collected from kidney donors to recipients in this study

Interventions

Tacrolimus with MMF DRUG

Standard dose Tacrolimus and MMF. This will follow standard of care procedures at Northwestern Memorial Hospital's Comprehensive Transplant Center. MMF trough or area under the concentration time curve (AUC) shall not be used to adjust dosing. In this group, Tacrolimus will be initiated according to our practice. The Tacrolimus dose will be adjusted from day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 10 ng/mL. From month 2 until Month 6, the target Tacrolimus trough level will be reduced to 6 ng/mL to 8 ng/mL. After month 6, the target level of Tacrolimus will be reduced to 4 ng/mL to 8 ng/mL.

Also known as: Tacrolimus, FK 506, mycophenolate mofetil, MMF

Group 1: Tacrolimus with MMF.

Group 2: Tacrolimus with Everolimus. DRUG

From day 5 on, the starting dose of Everolimus (0.75 mg bid) will be increased if the trough level is \< 3 ng/mL, or reduced if the trough level is \> 8 ng/mL. Tacrolimus will be initiated according to our practice. In this treatment arm, the Tacrolimus dose will be adjusted from day 3 on, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From month 2 until Month 6, the target Tacrolimus trough level will be 3 ng/mL to 6 ng/mL. After month 6, the Tacrolimus dose should be adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL. MMF dose will be initiated as 1 g b.i.d. (2 g/day). Adjustments should be made for adverse events including but not limited to gastrointestinal intolerance and a decrease in white blood cell (WBC).

Also known as: Everolimus, Zortress, Tacrolimus, FK 506

Group 2: Tacrolimus with Everolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects should be adults between 18 and 70 years of age
• Subjects can be either gender or of any ethnic background
• Subjects should be single organ recipients (kidney only)
• Subjects must be able to understand the protocol and provide informed consent.
• Recipient of living donor kidney transplants
• Panel reactive antibody (PRA) \< 20%

You may not qualify if:

• Subjects with End Stage Renal Disease (ESRD) secondary to primary focal segmental glomerulonephritis (FSGS).
• Inability to fully understand the purpose of the study and the inability to sign the informed consent
• Subjects with a significant or active infection
• Subjects who are pregnant or nursing females
• Subjects with a history of severe hyperlipidemia not controlled with statins, patients with Cholesterol \> 400mg/dl
• Subjects with a platelet count \< 100,000mm3, WBC \< 2,000mm3 (or clinical practice)
• Subjects, who, due to the existence of a surgical, medical or psychiatric condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment into this trial.

Sponsors & Collaborators

• Northwestern University: lead
• Novartis: collaborator

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

Tacrolimus; Mycophenolic Acid; Everolimus

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lorenzo Gallon, MD
• Organization: Northwestern University

l-gallon@northwestern.edu

312-695-4457

Study Officials

• Lorenzo Gallon, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: Associated Professor of Transplant Nephrology

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: July 31, 2012
• Study Start: February 1, 2013
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: March 2, 2021
• Results First Posted: March 2, 2021

Record last verified: 2021-02

Locations

US (1)