Study of Everolimus in de Novo Renal Transplant Recipients

Evaluation of the Early Conversion From a Calcineurin Inhibitor-based Immunosuppressive Regimen to Everolimus in de Novo Renal Transplant Recipients, a Multicenter Experience

In the present study, the investigators propose a conversion scheme with 50% reduction in CNI dosage until adjustment of everolimus dosage, in order to reach a trough blood level of 6-10 ng/mL, thus avoiding overimmunosuppression or alternatively breakthrough rejection episodes.

The hypothesis of this study is to demonstrate that the therapeutic regimen with Myfortic® and Certican® significantly improves renal function compared with the standard regimen of CNI.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Failure With Renal Transplant
• Intervention / Treatment: Drug: Everolimus

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • MG
    • Divinópolis, MG, Brazil, 35500-227
      • Hospital São João de Deus/Fundação Geraldo Corrêa
    • Ipatinga, MG, Brazil, 35160-158
      • Hospital Márcio Cunha/Fundação São Francisco Xavier
    • Juiz de Fora, MG, Brazil, 36036-330
      • Fundação IMEPEN
    • Montes Claros, MG, Brazil, 39400-103
      • Hospital do Rim de MOntes Claros/Irmandade Nossa Senhora das Mercês

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Renal transplant patients
• Age between 18 and 85 years
• Recipients of living or deceased donors
• Donor under the age of 85 years
• Panel Reactivity Antibodies (PRA) over or equal to 30%
• 4-5 months post-transplant
• CNI-based immunosuppressive regimen
• Stable graft function (creatinine lower than 2.0 mg/dl)
• No currently acute rejection
• Proteinuria lower than 800mg/d
• No laboratory or physical clinically significant signs presented for the last 2 months before screening.

Exclusion Criteria:

• Recipient of multiple organs
• Recipient with a history of focal segmental glomerulosclerosis or membranous glomerulonephritis
• Presence of uncontrolled hypercholesterolemia (≥350 mg/dL)hypertriglyceridemia (over or equal to 500 mg/dL)
• Patients with eGFR lower than 40 ml/min/1.73m2
• Evidence of acute rejection within 2 months before screening
• Thrombocytopenia (lower than 75,000/mm3)
• Neutropenia (lower than 1,500/mm3)
• Leukocytopenia (lower than 2500/mm3)
• Anemia (hemoglobin lower than 6.0g/dL)
• Severe liver disease (including transaminases or bilirubin equal or over 3 times normal)
• Proteinuria over 800mg/dL
• Systemic infection or pneumonia (active infection)
• Positive for Hepatitis B, Hepatitis C or HIV.

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
No Intervention: Control; 35 patients using Cyclosporin or Tacrolimus (C0=100-200/5-10ng/mL)+ Myfortic® 1440mg/dia + Steroids. Medications will be administered orally, twice a day
Active Comparator: Intervention; 35 randomized Patients Converted to Certican® (Everolimus C0=6-10 ng/mL) + Myfortic® 1440mg/day + Steroids. On the day of conversion (day 1), 2 mg everolimus will be introduced in the morning and at night, as morning dose of CsA or Tac will be maintained and evening dose of CsA or Tac will be reduced by 50%. In two days, 2 mg everolimus will be associated with 50% of CsA or Tac original dosage, both in the morning and evening. After that, everolimus dose will be adjusted to achieve a C0 target level of 6-10 ng/mL. Once target levels of everolimus are met, the CNI drug will be suspended.	Drug: Everolimus; On the day of conversion (day 1), 2 mg everolimus will be introduced in the morning and at night, as morning dose of CsA or Tac will be maintained and evening dose of CsA or Tac will be reduced by 50%. In two days, 2 mg everolimus will be associated with 50% of CsA or Tac original dosage, both in the morning and evening. After that, everolimus dose will be adjusted to achieve a C0 target level of 6-10 ng/mL. Once target levels of everolimus are met, the CNI drug will be suspended.; Other Names: Certican

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate (eGFR)	The eGFR will be calculated by Cockcroft-Gault, CKD-EPI and MDRD equations, firstly 4-5 months after transplantation (baseline), and then 6 and 12 months after conversion to everolimus (Certican ®) and suspension of CNI, associated with Myfortic ® (mycophenolate sodium enteric-coated - MSEC).	4-5 months after transplantation (baseline), and then 6 and 12 months after conversion to everolimus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
graft acute rejection	incidence of acute biopsy-proven rejection and clinical acute rejection (without biopsy), graft loss, death with a functioning graft, and loss of follow up at 6 and 12 months after conversion;	6 and 12 months after conversion
Laboratory results and clinical alterations	analyzing the incidence of anemia, thrombocytopenia, leukopenia, gastrointestinal side effects, pneumonitis, oral ulcers, edema, proteinuria, and any other adverse events, as well as the need of drug withdrawal	3, 6 and 12 months after conversion

Collaborators and Investigators

• Sponsor: Helady Pinheiro, MD, PhD
• Collaborators: Novartis
• Investigators: Principal Investigator: Hélady S Pinheiro, MD, PhD, Fundação IMEPEN

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: May 31, 2012
• First Posted (Estimate): June 1, 2012

Study Record Updates

• Last Update Posted (Estimate): June 12, 2013
• Last Update Submitted That Met QC Criteria: June 11, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Immunosuppression; Chronic Kidney Disease; Renal Transplant
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CRAD001ABR22T