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

Primary Purpose

Renal Allograft, Hepatitis C

Status

Completed

Phase

Phase 4

Locations

Brazil

Study Type

Interventional

Intervention

Everolimus

Cyclosporine

Tacrolimus

About this trial

This is an interventional supportive care trial for Renal Allograft focused on measuring Renal allograft recipients, Hepatitis C virus (HCV), Certican, Calcineurin inhibitor(tacrolimus or cyclosporin)

Eligibility Criteria

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

Inclusion criteria

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.

Exclusion criteria:

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;
Fasting triglycerides ≥ 400 mg/dL, fasting total cholesterol ≥ 350 mg/dL or LDL-cholesterol ≥ 160mg/dL despite the use of optimal lipid-lowering therapy;
History of malignancy within 3 years before enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin;
Subjects who are known to be human immunodeficiency virus (HIV) positive or hepatitis B positive;
Chronic hepatic failure.

Sites / Locations

Irmandade Da Santa Casa de Misericórdia de Porto Alegre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Certican®

Tacrolimus or Cyclosporine

Arm Description

Arm1(conversion):Certican®+mycophenolate+prednisone

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Incidence of acute allograft rejection

All patients will perform at least 07 protocol visits and should be performed renal biopsy during screening phase and during the follow up if present renal dysfunction or proteinuria.

Incidence of significant infections

During the study visits the patient will be evaluated by a doctor and it will perform blood tests to assess their clinical conditions.

Development of proteinuria

Spot urine sample for protein and creatinine will be performed.

Development of malignance

Medical evaluation will be performed during the protocol visits and if necessary biopsy and exams of imaging to confirm any suspected.

Development of dyslipidemia

Lipid levels: total cholesterol, HLD, LDL and triglycerides will be performed.

Development of liver impairment

Blood chemistry: TGO/AST, TGP/ALT , GGT and alkaline phosphatase will be performed.

Development of post-transplant diabetes

Blood chemistry: Glucose will be performed.

Development of hypertension

Vital signs will be performed

Graft loss survival

Graft survival will be evaluated by our team doctor.

Patient survival

Subject survival will be evaluated by our team doctor

Full Information

NCT ID

NCT01469884

First Posted

November 1, 2011

Last Updated

April 1, 2015

Sponsor

Irmandade Santa Casa de Misericórdia de Porto Alegre

Collaborators

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT01469884

Brief Title

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

Acronym

CONCERVIC

Official Title

A Prospective, Single-center, Open-label, Pilot Study to Investigate the Effect of Switching to Certican® in Viremia of Hepatitis C Virus in Adult Renal Allograft Recipients.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Completed

Study Start Date

November 2011 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Irmandade Santa Casa de Misericórdia de Porto Alegre

Collaborators

Novartis

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

Detailed Description

The infection by hepatitis C virus (HCV) is the leading cause of chronic liver disease in renal transplant recipients. The prevalence of pretransplantation anti-HCV is 11% to 49%. The impact of HCV infection on patient survival after renal transplant remains controversial. Some studies also showed that patients undergoing renal transplantation anti-HCV positive are associated with a reduction in graft and patient survival.Chronic infection of HCV is associated with an increased number of infections. In HCV positive renal transplant patients have been shown that there is an increase from four to seven times in HCV viremia after transplantation compared to pretransplant. To prevent viral replication, immunosuppression must be adapted, involving a balance between control of viral replication and rejection. Biochemically, the NS5A protein has been linked to increased replication of the hepatitis C virus through p70S6K phosphopeptides. Sirolimus as inhibitor of pathway mTOR/p70S6K reduced in vivo phosphorylation of NS5A phosphopeptides and thus viral replication. Moreover, the mTOR protein has been proven in vitron to have a protective role against apoptosis in HCV infected cells (WAGNER et al., 2010). Wagner et al. (2010) showed a beneficial effect of sirolimus on viral recurrence monitored by transaminases and viral load as well as by histological data. They also reported the improved survival after liver transplantation due to hepatitis C for patients receiving sirolimus rather than calcineurin inhibitor-based regimens. In the literature there have already been reported good virological control of HCV among liver transplant recipients after conversion to SRL and the reduction of hepatitis C virus recurrence (GALLEGO et al., 2009; BENEDETTOET al., 2010). Everolimus has shown a potent inhibitor of mTOR and has been widely used as an immunosuppressive agent in kidney transplant, but no reported effects on HCV progression was found in the literature.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Allograft, Hepatitis C

Keywords

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

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Certican®

Arm Type

Experimental

Arm Description

Arm1(conversion):Certican®+mycophenolate+prednisone

Arm Title

Tacrolimus or Cyclosporine

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Everolimus

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Cyclosporine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

Incidence of acute allograft rejection

Description

All patients will perform at least 07 protocol visits and should be performed renal biopsy during screening phase and during the follow up if present renal dysfunction or proteinuria.

Time Frame

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

Title

Incidence of significant infections

Description

During the study visits the patient will be evaluated by a doctor and it will perform blood tests to assess their clinical conditions.

Time Frame

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

Title

Development of proteinuria

Description

Spot urine sample for protein and creatinine will be performed.

Time Frame

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

Title

Development of malignance

Description

Medical evaluation will be performed during the protocol visits and if necessary biopsy and exams of imaging to confirm any suspected.

Time Frame

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

Title

Development of dyslipidemia

Description

Lipid levels: total cholesterol, HLD, LDL and triglycerides will be performed.

Time Frame

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

Title

Development of liver impairment

Description

Blood chemistry: TGO/AST, TGP/ALT , GGT and alkaline phosphatase will be performed.

Time Frame

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

Title

Development of post-transplant diabetes

Description

Blood chemistry: Glucose will be performed.

Time Frame

Months 1, 3, 6, 9 and 12

Title

Development of hypertension

Description

Vital signs will be performed

Time Frame

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

Title

Graft loss survival

Description

Graft survival will be evaluated by our team doctor.

Time Frame

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

Title

Patient survival

Description

Subject survival will be evaluated by our team doctor

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria 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. Exclusion criteria: 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; Fasting triglycerides ≥ 400 mg/dL, fasting total cholesterol ≥ 350 mg/dL or LDL-cholesterol ≥ 160mg/dL despite the use of optimal lipid-lowering therapy; History of malignancy within 3 years before enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin; Subjects who are known to be human immunodeficiency virus (HIV) positive or hepatitis B positive; Chronic hepatic failure.

Overall Study Officials: