NCT01134952

Brief Summary

Different immunosuppressive drugs used in transplantation may reduce the body's defences against infection differently. It is known that patients with Hepatitis C virus, known as HCV, who switched from azathioprine to mycophenolate mofetil experienced an increase in viral load. Despite this, mycophenolate mofetil is used because it prevents rejection more reliably than azathioprine. Sirolimus is an another immunosuppressive agent that reliably prevents rejection and may have antiviral activity. This study is designed to see if the viral load of HCV and other viruses is reduced by switching from mycophenolate to sirolimus.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
11

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jun 2010

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

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

May 27, 2010

Completed
5 days until next milestone

Study Start

First participant enrolled

June 1, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 2, 2010

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
2 months until next milestone

Results Posted

Study results publicly available

January 21, 2015

Completed
Last Updated

February 26, 2015

Status Verified

February 1, 2015

Enrollment Period

4.5 years

First QC Date

May 27, 2010

Results QC Date

December 15, 2014

Last Update Submit

February 6, 2015

Conditions

Hepatitis C

Keywords

sirolimuseverolimusmycophenolic acidhepatitis C virustacrolimusviral load

Outcome Measures

Primary Outcomes (1)

  • Delta Hepatitis C Viral Load

    Percent change in HCV load determined 3 months after switch from MMF to SRL.

    3 month

Secondary Outcomes (10)

  • Final Hepatitis C Viral Load

    3 month

  • Sirolimus Trough Level

    3 month

  • Delta Tacrolimus Trough Level

    3 month

  • Delta Bilirubin

    3 month

  • Delta Alkaline Phosphatase

    3 month

  • +5 more secondary outcomes

Study Arms (1)

Mycophenolate to sirolimus switch

EXPERIMENTAL

Liver transplant recipients with Hepatitis C virus switched from mycophenolate mofetil (MMF) to sirolimus (SRL) for 3 months and then switched back to MMF

Drug: Mycophenolate to sirolimus switch

Interventions

Mycophenolate to sirolimus switchDRUG

Sirolimus given for 3 months instead of mycophenolate at a starting dose equivalent of 1 mg sirolimus equal to 1000 mg of mycophenolate.

Also known as: rapamune, rapamycin, mycophenolic mofetil, mycophenolic acid, cellcept
Mycophenolate to sirolimus switch

Eligibility Criteria

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

You may qualify if:

  • Recurrent HCV after liver transplantation
  • Taking mycophenolate mofetil
  • Stable liver function

You may not qualify if:

  • Pregnant females or couples unwilling to use contraception
  • Intolerance or allergy to sirolimus
  • Patients taking anti-HCV therapy
  • Patients taking medications known to alter the levels of sirolimus
  • History of thromboembolic disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A5A5, Canada

Location

Related Publications (14)

  • Zekry A, Gleeson M, Guney S, McCaughan GW. A prospective cross-over study comparing the effect of mycophenolate versus azathioprine on allograft function and viral load in liver transplant recipients with recurrent chronic HCV infection. Liver Transpl. 2004 Jan;10(1):52-7. doi: 10.1002/lt.20000.

    PMID: 14755778BACKGROUND

  • McAlister VC, Gao Z, Peltekian K, Domingues J, Mahalati K, MacDonald AS. Sirolimus-tacrolimus combination immunosuppression. Lancet. 2000 Jan 29;355(9201):376-7. doi: 10.1016/S0140-6736(99)03882-9.

    PMID: 10665560BACKGROUND

  • Di Benedetto F, Di Sandro S, De Ruvo N, Montalti R, Ballarin R, Guerrini GP, Spaggiari M, Guaraldi G, Gerunda G. First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation. Transplantation. 2010 Mar 27;89(6):733-8. doi: 10.1097/TP.0b013e3181c7dcc0.

    PMID: 20048692BACKGROUND

  • 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: 19715912BACKGROUND

  • Samonakis DN, Cholongitas E, Triantos CK, Griffiths P, Dhillon AP, Thalheimer U, Patch DW, Burroughs AK. Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantation for HCV cirrhosis. J Hepatol. 2005 Dec;43(6):1091-3. doi: 10.1016/j.jhep.2005.08.005. Epub 2005 Sep 15.

    PMID: 16239045BACKGROUND

  • Ballardini G, De Raffele E, Groff P, Bioulac-Sage P, Grassi A, Ghetti S, Susca M, Strazzabosco M, Bellusci R, Iemmolo RM, Grazi G, Zauli D, Cavallari A, Bianchi FB. Timing of reinfection and mechanisms of hepatocellular damage in transplanted hepatitis C virus-reinfected liver. Liver Transpl. 2002 Jan;8(1):10-20. doi: 10.1053/jlts.2002.30141.

    PMID: 11799480BACKGROUND

  • Charlton M. Liver biopsy, viral kinetics, and the impact of viremia on severity of hepatitis C virus recurrence. Liver Transpl. 2003 Nov;9(11):S58-62. doi: 10.1053/jlts.2003.50245.

    PMID: 14586897BACKGROUND

  • Sindhi R, Webber S, Venkataramanan R, McGhee W, Phillips S, Smith A, Baird C, Iurlano K, Mazariegos G, Cooperstone B, Holt DW, Zeevi A, Fung JJ, Reyes J. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus. Transplantation. 2001 Sep 15;72(5):851-5. doi: 10.1097/00007890-200109150-00019.

    PMID: 11571449BACKGROUND

  • Nepomuceno RR, Balatoni CE, Natkunam Y, Snow AL, Krams SM, Martinez OM. Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas. Cancer Res. 2003 Aug 1;63(15):4472-80.

    PMID: 12907620BACKGROUND

  • Kneteman NM, Oberholzer J, Al Saghier M, Meeberg GA, Blitz M, Ma MM, Wong WW, Gutfreund K, Mason AL, Jewell LD, Shapiro AM, Bain VG, Bigam DL. Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma. Liver Transpl. 2004 Oct;10(10):1301-11. doi: 10.1002/lt.20237.

    PMID: 15376305BACKGROUND

  • Iacob S, Cicinnati VR, Hilgard P, Iacob RA, Gheorghe LS, Popescu I, Frilling A, Malago M, Gerken G, Broelsch CE, Beckebaum S. Predictors of graft and patient survival in hepatitis C virus (HCV) recipients: model to predict HCV cirrhosis after liver transplantation. Transplantation. 2007 Jul 15;84(1):56-63. doi: 10.1097/01.tp.0000267916.36343.ca.

    PMID: 17627238BACKGROUND

  • Kornberg A, Kupper B, Tannapfel A, Hommann M, Scheele J. Impact of mycophenolate mofetil versus azathioprine on early recurrence of hepatitis C after liver transplantation. Int Immunopharmacol. 2005 Jan;5(1):107-15. doi: 10.1016/j.intimp.2004.09.010.

    PMID: 15589468BACKGROUND

  • Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD005161. doi: 10.1002/14651858.CD005161.pub2.

    PMID: 17054241BACKGROUND

  • Rostaing L, Izopet J, Sandres K, Cisterne JM, Puel J, Durand D. Changes in hepatitis C virus RNA viremia concentrations in long-term renal transplant patients after introduction of mycophenolate mofetil. Transplantation. 2000 Mar 15;69(5):991-4. doi: 10.1097/00007890-200003150-00055.

    PMID: 10755563BACKGROUND

Related Links

MeSH Terms

Conditions

Hepatitis C

Interventions

SirolimusMycophenolic Acid

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipids

Limitations and Caveats

Greater than expected baseline variation; technical problems with laboratory measurement of HCV (two different platforms used); and poor recruitment over a long period make the results difficult to interpret.

Results Point of Contact

Title
Dr Vivian McAlister
Organization
LondonHSC
vmcalist@uwo.ca
5196632920

Study Officials

  • Vivian McAlister, MB, FRCSC

    London Health Sciences Centre

    STUDY DIRECTOR

  • Natasha Chandok, MD, FRCPC

    London Health Sciences Centre

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal investigator

Study Record Dates

First Submitted

May 27, 2010

First Posted

June 2, 2010

Study Start

June 1, 2010

Primary Completion

December 1, 2014

Study Completion

December 1, 2014

Last Updated

February 26, 2015

Results First Posted

January 21, 2015

Record last verified: 2015-02

Locations

CA(1)