Efficacy and Safety of Everolimus in de Novo Kidney Transplant Recipients of ECD or AKI Donors

A 12 Month, Single-center, Open-label, Randomized-controlled Trial to Investigate Efficacy, Safety and Tolerability of Everolimus in Combination With Cyclosporine A and Corticosteroid in de Novo Transplant Recipients of Expanded Criteria Donor Kidneys or Acute Kidney Injury

Single center, open-label randomized-control trial Population: de novo 48 kidney transplant recipients (age 18-75 years) from ECD/AKI donors Compare: everolimus with low dose CNI and prednisolone versus standard immunosuppressive regimen Objective: To evaluate efficacy of everolimus with low dose CNI in de novo kidney transplant recipients of ECD/AKI donors Primary endpoint: Mean eGFR (CKD-EPI) at 12 months post-transplantation

Study Overview

• Status: Unknown
• Conditions: Transplantation of Kidney; ECD; Expanded Criteria Donor
• Intervention / Treatment: Drug: Everolimus + low dose cyclosporin A + prednisolone; Drug: Standard immunosupressive regimen

Detailed Description

Secondary Endpoints:

• To assess renal function by means of eGFR (Cockcrault and Gault formula), at -Month 6 and 12 post-transplantation
• To assess incidence of the individual composite endpoints including BPAR, graft loss and death at Month 6 and 12 post-transplantation
• To assess the incidence and duration of renal replacement therapy
• To assess the incidence of chronic allograft nephropathy (IF/TA) at Month 12
• To assess renal function by means of serum creatinine at Month 6 and 12 post-transplantation
• To compare the overall safety and tolerability (incidence of AEs and SAEs, infections, discontinuations due to AEs, lab abnormalities, wound and surgical complications) at Month 6 and 12 post-transplantation

Definition of ECD

• Brain-dead donor > 60 years old or
• Donor age > 50 years old with two of the following criteria;
• History of HT
• Terminal SCr. ≥ 1.5 mg/dL
• Death from cerebrovascular accident Definition of AKI donor
• Brain-dead donor with an increase of SCr. ≥ 0.3 mg/dL from baseline

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-75 years
• Recipients of first DDKT from ECD or AKI donors
• Patient willing to participate in the study

Exclusion Criteria:

• Multi-organ recipients

  • Organ donation after Cardiac Death (DCD).
  • PRA > 20 % or with historical peak PRA > 50%
  • Patients who lost first graft due to immunological reason within the first year post-transplantation.
  • ABO incompatible transplants or positive cross-match
  • Patients with chronic inflammatory bowel disease.
  • Severe allergy requiring acute treatment, or any known hypersensitivity to everolimus, thymoglobulin
  • Thrombocytopenia (platelet < 75,000/mm3), ANC < 1,500 /mm3 or leucopenia (leucocytes < 2,500/mm3), or Hb < 6 g/dL
  • Chronic active HCV, HIV, or HBsAg positive
  • History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin.
  • Ongoing infection requiring treatment with a systemic antibiotic.
  • Patient with severe hypercholesterolemia (> 300 mg/dL) or hypertriglyceridemia (> 600 mg/dL) that cannot be controlled
  • Evidence of severe liver disease.
  • Severe restrictive or obstructive pulmonary disorders.
  • Pregnant or nursing (lactating) women.
  • Patient who refuse to participate into the study or would like to withdraw from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: investigation arm; De novo kidney transplantation form ECD/AKI donor with Everolimus + low dose cyclosporinA + prednisolone as immunosuppressive regimen	Drug: Everolimus + low dose cyclosporin A + prednisolone
Other: B: control arm; De novo kidney transplantation form ECD/AKI donor with standard immunosuppressive regimen	Drug: Standard immunosupressive regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
eGFR (CKD-EPI)	12 months post kidney transplantation

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Surasak Kantachuvesiri, M.D., PH.D, Ramathibodi Hospital, Mahidol University

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): June 1, 2015

Study Registration Dates

• First Submitted: December 8, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimate): December 11, 2014

Study Record Updates

• Last Update Posted (Estimate): December 11, 2014
• Last Update Submitted That Met QC Criteria: December 10, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Kidney transplantation; ECD
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Prednisolone; Everolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CRAD001ATH01T