Evaluation of Calcineurin-inhibitor Reduction With Conversion at 2 Months to Everolimus/Reduced Tacrolimus in Renal Transplant Recipients Following Campath® Induction

NCT ID: NCT01935128

Last Updated: 2022-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-03
• Study Completion Date: 2020-07-31

Brief Summary

The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival).

Detailed Description

The purpose of this study is to evaluate whether conversion to everolimus (Zortress®), allowing the elimination or reduction of calcineurin inhibitors, will reduce nephrotoxicity (measured by increased creatinine clearance) and lengthen overall graft (kidney transplant) survival (measured by 2-3 year graft survival). Among the worst of the long-term effects of chronic immunosuppression are the nephrotoxicity (toxic to kidney cells) of the calcineurin inhibitors and the myriad complications of steroids. This protocol evaluates the elimination or reduction of calcineurin inhibitors in a protocol that has already successfully eliminated the long-term use of steroids. A considerable need remains for safer therapeutic agents that inhibit T-cell activation (a white blood cell that attacks foreign cells as part of the immune response) via a calcineurin independent or reduced-dose mechanism of action.

Conditions

Renal Transplant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 Everolimus/Reduced dose tacrolimus

In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.

Group Type: EXPERIMENTAL

Arm 1 Everolimus/Reduced dose tacrolimus

Intervention Type: DRUG

Immunosuppression drug intervention

Interventions

Arm 1 Everolimus/Reduced dose tacrolimus

Immunosuppression drug intervention

Intervention Type: DRUG

Other Intervention Names

Zortress®; Prograf® or Hecoria®

Eligibility Criteria

Inclusion Criteria

• Male or female renal allograft recipients at least 18 years old.
• Patients who have given written informed consent to participate in the study. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
• Patient who has received a kidney transplant from a deceased or living unrelated-/related donor.
• Recipient of a kidney allograft with a cold ischemia time (CIT) < 36 hours.
• Female patients must have a negative pregnancy test prior to study enrollment.
• Patients on calcineurin inhibitor(s) (CNI) (tacrolimus and myfortic®) without steroid maintenance following Campath® induction.
• Patients with an acceptable allograft function defined by a serum creatinine < 2.5 mg/dL (250 μmol/L) and an actual estimated glomerular filtration rate (eGFR) (Modification of diet in renal disease equation 4, MDRD4) ≥ 30 mL/min/1.73m2 (without renal replacement therapy).
• No evidence of rejection since the time of transplantation.

Exclusion Criteria

• Recipient of ABO incompatible allograft or a positive cross-match.
• Patient who is human immunodeficiency virus (HIV) positive.
• Patient who received an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
• HBsAg and/or a HCV positive patient with evidence of elevated liver function tests (LFTs) (Alanine transaminase/Aspartate transaminase [ALT/AST] levels ≥ 2.5 times upper limit of normal [ULN]). Viral serology results obtained within 6 months prior to randomization are acceptable.
• Patient with severe restrictive (total lung capacity [TLC] < 50%) or obstructive pulmonary (forced expiratory volume in one second [FEV1] < 50) disorders.
• Patient with severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment that would prevent patient from potential exposure to everolimus, or with hypersensitivity to drugs similar to everolimus (e.g. macrolides).
• Patients with a known hypersensitivity/contraindication to any of the immunosuppressants or their classes, or to any of the excipients.
• Patient with severe hypercholesterolemia (> 300 mg/dL) or hypertriglyceridemia (> 400 mg/dL) that cannot be controlled despite lipid lowering therapy.
• Patient with white blood cell (WBC) count ≤ 1,000 /mm3 (and absolute neutrophil count [ANC] of <500) or a platelet count ≤ 50,000 /mm3.
• History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. (Localized basal cell carcinoma of the skin at any time, or small (less than 4 cm) or low-grade renal cancers, bladder cancers, or treated prostate cancer with no evidence of disease after 2 years are allowable)
• Graft loss.
• Patient on renal replacement therapy.
• Patient who experienced biopsy proven rejection.
• Proteinuria > 1 g/day (as calculated from the urinary protein-to-creatinine ratio).
• Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).
• Patient who has a current severe systemic infection according to the investigator judgment requiring continued therapy that would interfere with the objectives of the study.
• Patients with ongoing wound healing problems, clinically significant infection requiring continued therapy or other severe surgical complication in the opinion of the investigator.
• Presence of intractable immunosuppressant complications or side effects.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL)
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University of Toledo Health Science Campus

OTHER

Sponsor Role: lead

Responsible Party

Michael A. Rees, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Rees, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Toledo, HSC

Locations

University of Toledo, Health Science Campus

Toledo, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Everolimus

Identifier Type: -

Identifier Source: org_study_id