Study of Everolimus in de Novo Renal Transplant Recipients

End Stage Renal Failure With Renal Transplant Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01609673
• Other study ID #: CRAD001ABR22T
• Status: Terminated
• Phase: N/A
• First received: May 24, 2012
• Last updated: June 11, 2013
• Start date: March 2013
• Est. completion date: May 2013

Study information

• Verified date: June 2013
• Source: Fundação Instituto Mineiro de Estudo Pesquisa Em Nefrologi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End Stage Renal Failure With Renal Transplant
• Kidney Failure, Chronic

Intervention

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.

Locations

Country	Name	City	State
Brazil	Hospital São João de Deus/Fundação Geraldo Corrêa	Divinópolis	MG
Brazil	Hospital Márcio Cunha/Fundação São Francisco Xavier	Ipatinga	MG
Brazil	Fundação IMEPEN	Juiz de Fora	MG
Brazil	Hospital do Rim de MOntes Claros/Irmandade Nossa Senhora das Mercês	Montes Claros	MG

Sponsors (2)

Lead Sponsor	Collaborator
Helady Pinheiro, MD, PhD	Novartis

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes