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Renal AllograftPhase 4CONCERVICNCT01469884

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

A Phase 4 study testing Everolimus, Cyclosporine and Tacrolimus in people with Renal Allograft and Hepatitis C, run by Irmandade Santa Casa de Misericórdia de Porto Alegre at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Allograft, Hepatitis C
What is being tested?
Everolimus, Cyclosporine and Tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteBrazil
Study dates
Nov 2011to Apr 2015
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 19Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Irmandade Da Santa Casa de Misericórdia de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90020090

Other trials in Brazil

About this study

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.

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

Read the 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.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    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.

  • CyclosporineDrug

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

  • TacrolimusDrug

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

Study groups in NCT01469884
Study groupRoleWhat they receive
Certican®ExperimentalArm1(conversion):Certican®+mycophenolate+prednisone
Receives: Drug: Everolimus
Tacrolimus or CyclosporineActive comparatorArm2(maintained):Tacrolimus or Cyclosporine+mycophenolate+prednisone
Receives: Drug: Cyclosporine; Drug: Tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

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

Secondary outcomes (10)

  1. 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.

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

  2. 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.

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

  3. Development of proteinuria

    Spot urine sample for protein and creatinine will be performed.

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

  4. Development of malignance

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

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

  5. Development of dyslipidemia

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

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

  6. Development of liver impairment

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

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

  7. Development of post-transplant diabetes

    Blood chemistry: Glucose will be performed.

    Measured: Months 1, 3, 6, 9 and 12

  8. Development of hypertension

    Vital signs will be performed

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

  9. Graft loss survival

    Graft survival will be evaluated by our team doctor.

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

  10. Patient survival

    Subject survival will be evaluated by our team doctor

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionApr 2015
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01469884
Sponsor's protocol ID
CRAD001
Other IDs
CRAD001ABR20T
Acronym
CONCERVIC
Status last verified
Apr 2015
First submitted
1 Nov 2011
Last updated
3 Apr 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

  • 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.

    PubMed 12493421

  • 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.

    PubMed 19715912

  • 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.

    PubMed 17580153

  • Mas, V.; Alvarellos, T.; Chiurchiu, C.; Camps, D.; Massari, P.; Boccardo, G. Hepatitis C Virus Infection After Renal Transplantation: Viral Load and Outcome. Transplantation Proceedings, 33, 1791-1793, 2001. Ridruejo, E.; Cusumano, A.; Diaz, C.; Dávalos Michel. M.; Jost, L.; Jost, L.; Soler Pujol, G.; Mandó, O. G.; Vilches, A. Hepatitis C Virus Infection and Outcome of Renal Transplantation. Transplantation Proceedings , 39, 3127-3130, 2007.

  • 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.

    PubMed 11477346

  • 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.

    PubMed 20483386

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Everolimus, Cyclosporine and Tacrolimus in people with Renal Allograft and Hepatitis C, run by Irmandade Santa Casa de Misericórdia de Porto Alegre at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in viral load of hepatitis C virus at 12 months after randomization. (time frame: Baseline,Months 3, 6, 9 and 12 after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01469884, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2015.

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