A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys

NCT01878786 | Terminated Phase 2 Results DMC

• 1 other identifier: IIRPCRAD001AUS183T
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to evaluate concentration-controlled everolimus with low dose tacrolimus compared to early conversion to CNI-free regimen and MMF/MPA with standard dose tacrolimus in de novo renal transplant recipients of ECD/DCD kidneys. Given tacrolimus and MMF/MPA is a widely prescribed immunosuppressive regimen in the United States, comparisons of tacrolimus and MMF/MPA regimens to investigational therapies and treatment regimens are needed. Also, considering the fact that ECD/DCD is a fast growing fraction of donors, evaluation of various regimens' effects on rather delicate ECD/DCD kidneys is necessary.

Conditions

Delayed Graft Function

Keywords

kidney failure

Outcome Measures

Primary Outcomes (1)

• Evaluate Concentration-controlled Everolimus and Low Dose Tacrolimus Compared to MMF/MPA With Standard Dose Tacrolimus at 24 Months

  The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.

  24 months

Secondary Outcomes (1)

• Compare Renal Function of the Everolimus Treatment Arms to the MMF/MPA Treatment Arm at 12 and 24 Months Post-transplantation

  24 months

Other Outcomes (1)

• Incidence of Cytomegalovirus (CMV) (Viremia or Viruria)

  24 months

Study Arms (3)

ERL & TAC

EXPERIMENTAL

Concentration controlled everolimus(ERL) \& Low dose tacrolimus(TAC) + corticosteroid withdraw

Drug: Everolimus; Drug: Tacrolimus

ERL & TAC --> MMF/MPA

EXPERIMENTAL

Concentration controlled everolimus \& low dose tacrolimus --\> mycophenolate mofetil (MMF) at Month 3 + corticosteroid

Drug: Everolimus; Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF/MPA)

Standard dose TAC + MMF/MPA

EXPERIMENTAL

Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw

Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF/MPA)

Interventions

Everolimus DRUG

One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus .

Also known as: Zortress

ERL & TAC; ERL & TAC --> MMF/MPA

Tacrolimus DRUG

One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus.

Also known as: Prograf

ERL & TAC; ERL & TAC --> MMF/MPA; Standard dose TAC + MMF/MPA

Mycophenolate mofetil (MMF/MPA) DRUG

Control Drug

Also known as: CellCept

ERL & TAC --> MMF/MPA; Standard dose TAC + MMF/MPA

Eligibility Criteria

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

You may qualify if:

• Male or female recipients 18-65 years of age undergoing primary or secondary kidney transplantation
• Recipients of primary or secondary cadaveric, ECD/DCD kidney (defined as follows)
• Donor whose heart has irreversibly stopped beating, previously referred to as non-heart-beating or asystolic donation
• Brain-dead donor \> 60 years old
• Donor aged 50-59 years old with two of the following criteria:
• History of hypertension
• Terminal serum creatinine ≥ 1.5 mg/dL
• Death resulting from cerebrovascular accident
• Patients who have given written informed consent to participate in the study

You may not qualify if:

• Cold ischemic time (CIT) \> 30 hours
• Patients who are ABO incompatible transplants, or T, or B cell crossmatch positive transplant
• Patients with a known hypersensitivity to any of the study drugs or to drugs of similar chemical class
• Non-controlled DCD
• Donor age \>70
• Patients with BMI \>32 at baseline before surgery
• Pregnant or lactating females
• Females of childbearing potential unwilling to use an effective means of contraception or are planning to become pregnant
• Patients with platelet count \<100,000/mm3 at the evaluation before randomization.
• Patients with an absolute neutrophil count of \< 1,500/mm³ at baseline before surgery or white blood cell count of \< 4,500/mm³
• Patients who are recipients of multiple solid organ transplants
• Patients who have severe hypercholesterolemia (\>350 mg/dL; \>9 mmol/L) or hypertriglyceridemia (\>500 mg/dL; \>5.6 mmol/L). Patients with controlled hyperlipidemia are acceptable
• Patients who have an abnormal liver profile such as ALT, AST, Alk Phos or total bilirubin \>3 times the upper normal limit
• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4, such as terfenadine, astemizole, cisapride, erythromycin, azithromycin, itraconazole, rifampin or lovastatin
• Patients who received an investigational drug or who have been treated with a non-protocol immunosuppressive drug or treatment within 30 days or 5 half-lives prior to randomization

Sponsors & Collaborators

• Matthew Cooper: lead

Study Sites (1)

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Delayed Graft Function; Renal Insufficiency

Interventions

Everolimus; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

Limitations and Caveats

The study was terminated prematurely and analysis was not performed on the incomplete data.

Results Point of Contact

• Title: Dr. Matthew Cooper
• Organization: MedStar Georgetown Transplant Institute

Matthew.Cooper@gunet.georgetown.edu

202-444-0753

Study Officials

• Matthew Cooper

  Georgetown University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Matthew Cooper

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 17, 2013
• Study Start: June 1, 2013
• Primary Completion: November 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 26, 2019
• Results First Posted: April 26, 2019

Record last verified: 2019-04

Locations

US (1)