Effect of Switching to Certican® in Viremia of Hepatitis C Virus in Adult Renal Allograft Recipients

NCT01469884 | Completed Phase 4

• 2 other identifiers: CRAD001CRAD001ABR20T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Compare the viral load of hepatitis c virus in patients converted to certican versus patients who are maintained on calcineurin inhibitor.

Conditions

Renal Allograft; Hepatitis C

Keywords

Renal allograft recipients; Hepatitis C virus (HCV); Certican; Calcineurin inhibitor(tacrolimus or cyclosporin)

Outcome Measures

Primary Outcomes (1)

• Change from baseline in viral load of hepatitis C virus at 12 months after randomization.

  HCV viremia will be measured by polymerase chain reaction (PCR)

  Baseline,Months 3, 6, 9 and 12 after randomization

Secondary Outcomes (10)

• Incidence of acute allograft rejection

  Weeks 1, 2, 3, months 1, 3, 6, 9 and 12 after randomization

• Incidence of significant infections

  Weeks1, 2, 3 and months 1, 3, 6,9 and 12 after randomization

• Development of proteinuria

  Months 1, 3, 6, 9 and 12 after randomization

• Development of malignance

  Weeks 1, 2, 3 and months 1, 3, 6, 9 and 12 after randomization

• Development of dyslipidemia

  Months 1, 3, 6, 9 and 12 after randomization

Study Arms (2)

Certican®

EXPERIMENTAL

Arm1(conversion):Certican®+mycophenolate+prednisone

Drug: Everolimus

Tacrolimus or Cyclosporine

ACTIVE COMPARATOR

Arm2(maintained):Tacrolimus or Cyclosporine+mycophenolate+prednisone

Drug: Cyclosporine; Drug: Tacrolimus

Interventions

Everolimus DRUG

The conversion will be performed abruptly for all patients. Calcineurin inhibitor will be discontinued one day before the day of conversion (Day 1). Everolimus will be introduced on day 1 at dose of 3 mg/d (1,5mg bid), and then everolimus trough levels will be adjusted to achieve 6-10 ng/ml.

Certican®

Cyclosporine DRUG

Trough level should be between 100 and 200ng/ml.

Tacrolimus or Cyclosporine

Tacrolimus DRUG

Trough level should be between 5 and 10ng/ml.

Tacrolimus or Cyclosporine

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at the time of screening;
• Subjects between the first and tenth year after renal transplantation;
• Subjects with positive serology for hepatitis C;
• Subjects receiving calcineurin inhibitor (tacrolimus or cyclosporine) plus mycophenolate sodium or mofetil plus prednisone since the first month post-transplant;
• Subjects with no acute rejection episode in the last 3 month;
• Women of childbearing potential (CBP) with a negative pregnancy test at screening (urine or serum;
• Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study. The investigator will determine which contraceptive method more effective and appropriate for each study subject. Acceptable methods of contraception include oral contraceptives, barrier methods (eg, diaphragm or condom with spermicide) and intrauterine devices.

You may not qualify if:

• Subjects who, in the opinion of the investigator, are not able to complete the study;
• Recipients of multiple organ transplant (i.e., prior or concurrent transplantation of a non-renal allograft;
• Subjects with a calculated GFR \< 30ml/min (abbreviated MDRD formula;
• Subjects with Urinary protein/creatinine \> 0.5;
• Renal biopsy with score ≥ Banff grade II interstitial fibrosis and tubular atrophy (Banff 2007;
• Subjects with a history of biopsy-proven acute rejection within 12 weeks of enrollment;
• Known or suspected hypersensitivity to inhibitor of mTOR;
• Subjects with a history of primary or recurrent FSGS, membranous glomerulonephritis (MGN) or membranoproliferative glomerulonephritis (MPGN);
• Evidence of any active systemic or localized major infection;
• Use of any investigational drug or treatment up to 4 weeks before enrollment;
• Immunosuppressive therapies other than those described by this protocol;
• Planned systemic treatment with voriconazole, cisapride or ketoconazole that will not be discontinued before randomization;
• Prior treatment with aminoglycosides, amphotericin B, cisplatin or other drugs associated with renal dysfunction that is not discontinued before screening;
• Subjects with a screening total white blood cell count (WBC) ≤ 2000/mm3, hemoglobin ≤ 10g/dL and platelet count ≤ 100000/mm3;
• TGO/AST, TGP/ALT and bilirubins with values three times higher than reference values;

Sponsors & Collaborators

• Irmandade Santa Casa de Misericórdia de Porto Alegre: lead
• Novartis: collaborator

Study Sites (1)

Irmandade Da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020090, Brazil

Location

Related Publications (7)

• Benedetto, F. D.; Sandro, S. D.; Ballarin, R.; Guaraldi, G.; Gerunda, G. E. Rapamycin and HIV Replication in Liver Transplant Recipients. Transplantation, 9, 1040, 2010.

  BACKGROUND

• Boletis JN, Iniotaki-Theodoraki A, Psichogiou M, Stamatiadis DN, Viglis JV, Kostakis A, Stavropoulos-Giokas C. Immune status in renal transplant recipients with hepatitis C virus infection. Transplant Proc. 2002 Dec;34(8):3205-8. doi: 10.1016/s0041-1345(02)03656-4. No abstract available.

  PMID: 12493421 BACKGROUND

• Gallego R, Henriquez F, Oliva E, Camacho R, Hernandez R, Hortal L, Sablon N, Quintana B, Santana R, Gonzalez F, Palop L, Vega N. Switching to sirolimus in renal transplant recipients with hepatitis C virus: a safe option. Transplant Proc. 2009 Jul-Aug;41(6):2334-6. doi: 10.1016/j.transproceed.2009.06.064.

  PMID: 19715912 BACKGROUND

• Ingsathit A, Thakkinstian A, Kantachuvesiri S, Sumethkul V. Different impacts of hepatitis B virus and hepatitis C virus on the outcome of kidney transplantation. Transplant Proc. 2007 Jun;39(5):1424-8. doi: 10.1016/j.transproceed.2007.02.068.

  PMID: 17580153 BACKGROUND

• Mas V, Alvarellos T, Chiurchiu C, Camps D, Massari P, de Boccardo G. Hepatitis C virus infection after renal transplantation: viral load and outcome. Transplant Proc. 2001 Feb-Mar;33(1-2):1791-3. doi: 10.1016/s0041-1345(00)02682-8. No abstract available.

  PMID: 11267514 BACKGROUND

• Meier-Kriesche HU, Ojo AO, Hanson JA, Kaplan B. Hepatitis C antibody status and outcomes in renal transplant recipients. Transplantation. 2001 Jul 27;72(2):241-4. doi: 10.1097/00007890-200107270-00013.

  PMID: 11477346 BACKGROUND

• Wagner D, Kniepeiss D, Schaffellner S, Jakoby E, Mueller H, Fahrleitner-Pammer A, Stiegler P, Tscheliessnigg KH, Iberer F. Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates. Int Immunopharmacol. 2010 Aug;10(8):990-3. doi: 10.1016/j.intimp.2010.05.006. Epub 2010 May 17.

  PMID: 20483386 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Interventions

Everolimus; Cyclosporine; Tacrolimus

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Valter Garcia, Physician

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  PRINCIPAL INVESTIGATOR

• ELIZETE KEITEL, Physician

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY CHAIR

• MARIANA F RODRIGUES, PHARMACIST

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• DIEGO GNATTA, PHARMACIST

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• LARISSA S PACHECO, PHARMACIST

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• BRUNA D CARDOSO, PHARMACIST

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• RONIVAN L DAL PRA, PHARMACIST

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PHYSICIAN NEPHROLOGY

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: November 10, 2011
• Study Start: November 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 3, 2015

Record last verified: 2015-04

Locations

BR (1)