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Study of Everolimus in de Novo Renal Transplant Recipients

Primary Purpose

End Stage Renal Failure With Renal Transplant

Status
Terminated
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Everolimus
Sponsored by
Helady Pinheiro, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Failure With Renal Transplant focused on measuring Immunosuppression, Chronic Kidney Disease, Renal Transplant

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital São João de Deus/Fundação Geraldo Corrêa
  • Hospital Márcio Cunha/Fundação São Francisco Xavier
  • Fundação IMEPEN
  • Hospital do Rim de MOntes Claros/Irmandade Nossa Senhora das Mercês

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Control

Intervention

Arm Description

35 patients using Cyclosporin or Tacrolimus (C0=100-200/5-10ng/mL)+ Myfortic® 1440mg/dia + Steroids. Medications will be administered orally, twice a day

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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;
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

Full Information

First Posted
May 24, 2012
Last Updated
June 11, 2013
Sponsor
Helady Pinheiro, MD, PhD
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT01609673
Brief Title
Study of Everolimus in de Novo Renal Transplant Recipients
Official Title
Evaluation of the Early Conversion From a Calcineurin Inhibitor-based Immunosuppressive Regimen to Everolimus in de Novo Renal Transplant Recipients, a Multicenter Experience
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Why Stopped
The inclusion of proposed sample turned to be infeasible due to Ethical Non-approval of 2 research sites and another site no transplant activity since 2012.
Study Start Date
March 2013 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Helady Pinheiro, MD, PhD
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Failure With Renal Transplant
Keywords
Immunosuppression, Chronic Kidney Disease, Renal Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm Description
35 patients using Cyclosporin or Tacrolimus (C0=100-200/5-10ng/mL)+ Myfortic® 1440mg/dia + Steroids. Medications will be administered orally, twice a day
Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Certican
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in estimated glomerular filtration rate (eGFR)
Description
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).
Time Frame
4-5 months after transplantation (baseline), and then 6 and 12 months after conversion to everolimus
Secondary Outcome Measure Information:
Title
graft acute rejection
Description
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;
Time Frame
6 and 12 months after conversion
Title
Laboratory results and clinical alterations
Description
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
Time Frame
3, 6 and 12 months after conversion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hélady S Pinheiro, MD, PhD
Organizational Affiliation
Fundação IMEPEN
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital São João de Deus/Fundação Geraldo Corrêa
City
Divinópolis
State/Province
MG
ZIP/Postal Code
35500-227
Country
Brazil
Facility Name
Hospital Márcio Cunha/Fundação São Francisco Xavier
City
Ipatinga
State/Province
MG
ZIP/Postal Code
35160-158
Country
Brazil
Facility Name
Fundação IMEPEN
City
Juiz de Fora
State/Province
MG
ZIP/Postal Code
36036-330
Country
Brazil
Facility Name
Hospital do Rim de MOntes Claros/Irmandade Nossa Senhora das Mercês
City
Montes Claros
State/Province
MG
ZIP/Postal Code
39400-103
Country
Brazil

12. IPD Sharing Statement

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Study of Everolimus in de Novo Renal Transplant Recipients

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