NCT01399242

Brief Summary

The primary objective is to demonstrate the superiority of everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at week 16 compared to tacrolimus plus Myfortic® plus corticosteroids as measured by the change in calculated Glomerular Filtration Rate (cGFR) from baseline to month 12. The key secondary objective is to demonstrate non-inferiority of biopsy-proved acute rejection (BPAR), graft loss, death or loss to follow-up (composite endpoint) at month 12 in patients switched to everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at Week 16 compared to patients maintained on tacrolimus plus Myfortic® plus corticosteroids. Patients will be submitted to monthly GFR determination but, for group comparison, only the GFR measured at month 12 and month 24 of renal transplantation will be used.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Aug 2011

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 20, 2011

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 21, 2011

Completed
11 days until next milestone

Study Start

First participant enrolled

August 1, 2011

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2013

Completed
Last Updated

July 21, 2011

Status Verified

March 1, 2011

Enrollment Period

10 months

First QC Date

June 20, 2011

Last Update Submit

July 20, 2011

Conditions

Disorder Related to Renal Transplantation

Keywords

Disorder Related to Renal Transplantation

Outcome Measures

Primary Outcomes (1)

  • Glomerular Filtration Rate

    The primary objective is to demonstrate the superiority of everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at week 16 compared to tacrolimus plus Myfortic® plus corticosteroids as measured by the change in calculated Glomerular Filtration Rate (cGFR) from baseline to month 12.

    96 weeks

Secondary Outcomes (1)

  • Non-inferiority of biopsy-proved acute rejection (BPAR), graft loss, death

    1 year after enrollment

Study Arms (2)

Certican, prednisona, EC-MPS

ACTIVE COMPARATOR

Twenty patients will be selected at 16 weeks of renal transplantation to convert a immunosuppression to certican,prednisone and myfortic. The allocation will be done randomly to provide similar epidemiological characteristics with respect to gender, age, renal function and co morbidities in the two groups. The informed consent will obtained after an interview involving the researcher and patient when the protocol will be explained.A protocol renal biopsy will be performed at the end of the study, 12 months after transplantation

Drug: Certican

Tacrolimus,Prednisona, EC-MPS

NO INTERVENTION

Twenty patients will be selected at 16 weeks of renal transplant to continue use EC-MPS,Tacrolimus and Prednisone. The allocation will be done randomly to provide similar epidemiological characteristics with respect to gender, age, renal function and co morbidities in the two groups. The informed consent will obtained after an interview involving the researcher and patient when the protocol will be explained.A protocol renal biopsy will be performed at the end of the study, 12 months after transplantation

Interventions

CerticanDRUG

Patients' therapy will be replaced from tacrolimus-based to everolimus-based immunosuppression. Everolimus will be introduced on day 1 at dose of 2 mg/day (1mg bid), and then everolimus trough levels will be obtained from day 3 onwards until C0 reaches the target for three consecutive days. Through levels will be adjusted to achieve 6-10ng/ml. Thereafter, if the target level was reached, the measurement will be performed weekly for 4 weeks and every 2 weeks until 8 weeks after conversion.In parallel, the tacrolimus dose will be reduced by 50% on day 1 and another 25% on day 7. The Tacrolimus will be withdrawn on day 14 if the target levels of everolimus are obtained.EC-MPS will be unchanged until day 14 after conversion.

Also known as: Myfortic, Prograf, Certican.
Certican, prednisona, EC-MPS

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women between 18-70 years old
  • Receptors of a first living-donor kidney allograft
  • Patients must have been on a tacrolimus+myfortic regimen for at least 2 weeks prior to randomization

You may not qualify if:

  • Patients with evidence of any acute rejection following transplantation at the time of randomization
  • GFR ≤ 35 ml/min
  • Proteinuria \> 800 mg/day
  • Recipients of multiple organ transplants
  • Chronic hepatic failure
  • Asymptomatic bacteriuria
  • Creatinine ≥ 2mg/dL on CNI withdrawn time
  • Proteinuria ≥ 1g/24h on CNI withdrawn time
  • Presence of uncontrolled hypercholesterolemia (≥ 350 mg/dL, ≥ 9.1 mmol/L)
  • Hypertriglyceridemia (≥ 500 mg/dL, ≥ 5.6 mmol/L)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Universitário São José

Belo Horizonte, Minas Gerais, 30140-073, Brazil

Location

Related Publications (10)

  • Pilmore HL, Dittmer ID. Calcineurin inhibitor nephrotoxicity: reduction in dose results in marked improvement in renal function in patients with coexisting chronic allograft nephropathy. Clin Transplant. 2002 Jun;16(3):191-5. doi: 10.1034/j.1399-0012.2002.01119.x.

    PMID: 12010142BACKGROUND

  • Mendez R, Gonwa T, Yang HC, Weinstein S, Jensik S, Steinberg S; Prograf Study Group. A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year. Transplantation. 2005 Aug 15;80(3):303-9. doi: 10.1097/01.tp.0000167757.63922.42.

    PMID: 16082323BACKGROUND

  • Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33. doi: 10.1056/NEJMoa020009.

    PMID: 14668458BACKGROUND

  • Lorber MI, Mulgaonkar S, Butt KM, Elkhammas E, Mendez R, Rajagopalan PR, Kahan B, Sollinger H, Li Y, Cretin N, Tedesco H; B251 Study Group. Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study. Transplantation. 2005 Jul 27;80(2):244-52. doi: 10.1097/01.tp.0000164352.65613.24.

    PMID: 16041270BACKGROUND

  • Johnson RW. The clinical impact of nephrotoxicity in renal transplantation. Transplantation. 2000 Jun 27;69(12 Suppl):SS14-7. doi: 10.1097/00007890-200006271-00004. No abstract available.

    PMID: 10910258BACKGROUND

  • Gallon L, Perico N, Dimitrov BD, Winoto J, Remuzzi G, Leventhal J, Gaspari F, Kaufman D. Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF. Am J Transplant. 2006 Jul;6(7):1617-23. doi: 10.1111/j.1600-6143.2006.01340.x.

    PMID: 16827862BACKGROUND

  • Tedesco-Silva H Jr, Vitko S, Pascual J, Eris J, Magee JC, Whelchel J, Civati G, Campbell S, Alves-Filho G, Bourbigot B, Garcia VD, Leone J, Esmeraldo R, Rigotti P, Cambi V, Haas T; 2306 and 2307 study groups. 12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients. Transpl Int. 2007 Jan;20(1):27-36. doi: 10.1111/j.1432-2277.2006.00414.x.

    PMID: 17181650BACKGROUND

  • Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roth D, Kupin W, Nicolas M, Ruiz P, Rosen A, Miller J. A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year. Transplantation. 2004 Jan 27;77(2):244-51. doi: 10.1097/01.TP.0000101290.20629.DC.

    PMID: 14742989BACKGROUND

  • Ciancio G, Burke GW, Gaynor JJ, Ruiz P, Roth D, Kupin W, Rosen A, Miller J. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis. Transplantation. 2006 Mar 27;81(6):845-52. doi: 10.1097/01.tp.0000203894.53714.27.

    PMID: 16570006BACKGROUND

  • Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roth D, Kupin W, Nicolas M, Ruiz P, Rosen A, Miller J. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year. Transplantation. 2004 Jan 27;77(2):252-8. doi: 10.1097/01.TP.0000101495.22734.07.

    PMID: 14742990BACKGROUND

MeSH Terms

Interventions

EverolimusMycophenolic AcidTacrolimus

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic ChemicalsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipids

Study Officials

  • Euler P lasmar

    Hospital Universitário Sao José

    STUDY DIRECTOR

Central Study Contacts

Marcus F lasmar

CONTACT

55-31-83351036marcuslasmar@hotmail.com

Luiz Flavio Giordano

CONTACT

55-31-91944606luizgiordano@uol.com.br

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 20, 2011

First Posted

July 21, 2011

Study Start

August 1, 2011

Primary Completion

June 1, 2012

Study Completion

June 1, 2013

Last Updated

July 21, 2011

Record last verified: 2011-03

Locations

BR(1)