Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation.

NCT01936519 | Completed Results DMC

• 1 other identifier: IRB 38115
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the renal sparing impact of implementing a strategy of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant

Conditions

Immunosuppression; Renal Failure

Keywords

Everolimus; Zortress; Renal Function; Tacrolimus; Cyclosporine; Myfortic; Mycophenolic Acid; Liver Transplantation

Outcome Measures

Primary Outcomes (5)

• Renal Function as Measured by 24 Hour Urine Creatinine Clearance

  Renal Function was assessed by 24 hr urine collection creatinine clearance measured (mL/min). 24 Hr urine collection was assessed at baseline, 6 months, 1 year, and 2 years post transplant.

  6 months, 1 year, and 2 years

• Renal Function as Measured by Serum Creatinine Level

  Serum creatinine levels were assessed at 6 months, 1 year, and 2 years post transplant

  6 months, 1 year, and 2 years

• Renal Function as Measured by Cockcroft Gault Creatinine Clearance

  The Cockcroft-Gault formula for estimating creatinine clearance was determined at 6 months, 1 year, and 2 years post transplant

  6 months, 1 year, and 2 years

• Renal Function as Measured by Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)

  Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR) was assessed at 6 months, 1 year, and 2 years post transplant.

  6 months, 1 year, and 2 years

• Renal Function as Measured by Iothalamate Clearance

  Iothalamate Clearance was assessed at 6 months, 1 year, and 2 years post transplant.

  6 months, 1 year, and 2 years

Other Outcomes (1)

• Recipient and Donor Genotyping for Selected Variants of CYP3A5, ABCB1 (MDR1), and CYP4A Genes

  2 years

Study Arms (2)

Calcineurin Inhibitor with Mycophenolic Acid

ACTIVE COMPARATOR

Calcineurin inhibitor immunosuppression with mycophenolic acid

Drug: Calcineurin Inhibitor

Everolimus with Mycophenolic Acid

EXPERIMENTAL

Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.

Drug: Arm A: Everolimus

Interventions

Arm A: Everolimus DRUG

Conversion to Everolimus immunosuppression combined with mycophenolic acid (Myfortic: MPA), and complete discontinuation of Calcineurin inhibitor at 3 months post transplant.

Also known as: Zortress; Mycophenolic Acid (Myfortic)

Everolimus with Mycophenolic Acid

Calcineurin Inhibitor DRUG

Comparison Arm: Continuation with standard immunosuppressive therapy consisting of Calcineurin inhibitor associated with mycophenolic acid (Myfortic: MPA).

Also known as: Tacrolimus (Prograf), Cyclosporine (Gengraf), Mycophenolic Acid (Myfortic)

Calcineurin Inhibitor with Mycophenolic Acid

Eligibility Criteria

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

You may qualify if:

• Ability and willingness to provide written informed consent and adhere to study regimen.
• Primary deceased donor liver transplant recipients 18-70 years of age
• Functioning allograft at randomization (AST, ALT, Total Bilirubin levels ≤3 times ULN, and AlkP and GGT levels ≤ 5 times ULN). Elevated GGT alone, in combination with AST, ALT, total bilirubin and AlkP within defined range does not exclude patients from randomization.
• Recipients on an immunosuppressive regimen of corticosteroids and tacrolimus.
• Confirmed recipient HCV status at Screening (either by serology or PCR).
• Abbreviated MDRD eGFR ≥ 30 mL/min/1.73m2. Local and central serum creatinine results within 5 days prior to randomization, however no sooner than Day 25 post-transplantation.
• Verification of at least one tacrolimus trough level of ≥ 8 ng/mL one week prior to randomization. Target trough levels above 8 ng/mL prior to randomization.
• Patients able to take oral medication at time of randomization.

You may not qualify if:

• Recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Combined liver kidney transplant recipients.
• Living donor or split liver recipients.
• History of malignancy of any organ system within past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.
• Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all \< 3 cm, per explant histology of recipient liver.
• Use of antibody induction therapy.
• Patients with known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
• Recipients of ABO incompatible transplant grafts.
• Recipients of Hepatitis B surface antigen or HIV donor organs.
• Surgical or medical condition, which might significantly alter absorption, distribution, metabolism and excretion of study drug.
• Women of child-bearing potential (WOCBP): 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 (1) they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \>40 mIU/m, or (2) have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy or (3) are using one or more of the following methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), copper coated IUD and double-barrier methods ( any double combination of male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout and for 3 months after study drug discontinuation.
• History of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed).
• Severe hypercholesterolemia (\>350 mg/dL; \>9 mmol/L) or hypertriglyceridemia (\>500 mg/dL; \>8.5 mmol/L) within 6 months of transplantation. Controlled hyperlipidemia is acceptable at time of randomization.
• Platelet count \< 50,000/mm3 at randomization.
• Absolute neutrophil count \< 1,000/mm³ or white blood cell count \<2,000/mm³ at randomization.
• Patients positive for HIV: Negative laboratory results within 6 months before randomization are acceptable.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Penn State College of Medicine; Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (29)

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MeSH Terms

Conditions

Renal Insufficiency

Interventions

Everolimus; Mycophenolic Acid; Calcineurin Inhibitors; Tacrolimus; Cyclosporine; Cyclosporins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr Zakiyah Kadry
• Organization: Penn State Milton S Hershey Medical Center

zkadry@pennstatehealth.psu.edu

717 531 5921

Study Officials

• Zakiyah Kadry, MD

  Penn State College of Medicine; Penn State Milton S Hershey Medical Center

  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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery; Chief, Division of Transplantation

Study Record Dates

• First Submitted: August 16, 2013
• First Posted: September 6, 2013
• Study Start: December 16, 2013
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: January 29, 2021
• Results First Posted: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)