Study of Everolimus in de Novo Renal Transplant Recipients

NCT01609673 | Terminated DMC

• 1 other identifier: CRAD001ABR22T
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 4

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.

Conditions

End Stage Renal Failure With Renal Transplant

Keywords

Immunosuppression; Chronic Kidney Disease; Renal Transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• graft acute rejection

  6 and 12 months after conversion

• Laboratory results and clinical alterations

  3, 6 and 12 months after conversion

Study Arms (2)

Control

NO INTERVENTION

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

Intervention

ACTIVE COMPARATOR

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

Interventions

Everolimus DRUG

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.

Also known as: Certican

Intervention

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helady Pinheiro, MD, PhD: lead
• Novartis: collaborator

Study Sites (4)

Hospital São João de Deus/Fundação Geraldo Corrêa

Divinópolis, Minas Gerais, 35500-227, Brazil

Location

Hospital Márcio Cunha/Fundação São Francisco Xavier

Ipatinga, Minas Gerais, 35160-158, Brazil

Location

Fundação IMEPEN

Juiz de Fora, Minas Gerais, 36036-330, Brazil

Location

Hospital do Rim de MOntes Claros/Irmandade Nossa Senhora das Mercês

Montes Claros, Minas Gerais, 39400-103, Brazil

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Hélady S Pinheiro, MD, PhD

  Fundação IMEPEN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: May 24, 2012
• First Posted: June 1, 2012
• Study Start: March 1, 2013
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 12, 2013

Record last verified: 2013-06

Locations

BR (4)