Hepatitis C Recurrence After Liver TransplantPhase 3NCT01707849

The Impact of Everolimus Based Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation

A Phase 3 study testing EVL arm and MMF arm in people with Hepatitis C Recurrence After Liver Transplant, run by Hospital Vall d'Hebron at 1 site in Spain.

Completed

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

Official record

Search all trials

Trial summary

Background: Hepatitis C recurrence, which invariably occurs in viremic liver transplant (LT) recipients, associated with accelerated liver fibrosis leading to established graft cirrhosis in 40-20% of patients in 5 years with another 5% experiencing an aggressive form with cirrhosis and graft loss in 1 year. Read more about this study

Who is it for?: Ages 18 to 68 years
Conditions the study is for: Hepatitis C Recurrence After Liver Transplant
What is being tested?: EVL arm and MMF arm
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteSpain
Study dates: Oct 2012to Aug 2016
Phase: Phase 3
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 to 68 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age≥18 years
First liver transplant
RNA-HCV positive within 12 months previous to the transplant

Who cannot join

Multiorgan transplant
Split liver
Fulminant hepatitis
ABO incompatible
HIV positive patients
Glomerular Filtration rate ≤60mL/min/1.73m2

Trial locations and contacts

1 site in 1 country.

Spain1 site

Department of HPB Surgery and Transplant, Hospital Vall d´Hebron
Barcelona, 08035

Other trials in Spain

About this study

Official title: An Unicenter, Prospective, Randomized, Pilot Study Comparing the Effect of Everolimus-containing Versus mTOR Inhibitor Free Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation.

Background:

Hepatitis C recurrence, which invariably occurs in viremic liver transplant (LT) recipients, associated with accelerated liver fibrosis leading to established graft cirrhosis in 40-20% of patients in 5 years with another 5% experiencing an aggressive form with cirrhosis and graft loss in 1 year. Since treatment after LT has a low efficacy, the overall survival of HCV-infected LT recipients is shorter than that of uninfected LT patients.

New immunosuppressive agents such as mTOR inhibitors (Everolimus/Sirolimus) reduce the risk of liver graft rejection, have antifibrotic properties and do not worsen HCV recurrence. Moreover new directly-acting antiviral agents have increased efficacy of interferon-based treatment but their use in LT recipients may be limited by side effects.

Hypothesis:

Use of individualized immunosuppressive regimen and early personalized anti-viral treatment based on recipient and viral factors would improve outcome of HCV infected liver transplant recipients.

Objectives:

To evaluate safety and efficacy of two steroid-free immunosuppressive regimens to reduce hepatitis C recurrence associated to fibrosis progression (F≥2 under ISHAK score) at one year post-transplant.
To identify viral and recipient factors associated with liver fibrosis progression using ultra-deep pyrosequencing (UDPS).

Read the detailed description

Study design:

A pilot, open-label, prospective, randomized and unicenter study. As pilot study, the number of patients expected to be included is n=40.

Inclusion criteria:

Age≥18 years
First liver transplant
RNA-HCV positive within 12 months previous to the transplant

Exclusion criteria:

Multiorgan transplant
Split liver
ABO incompatible
HIV positive patients
Glomerular Filtration rate ≤60mL/min/1.73m2

Patients will receive double immunosuppression therapy at induction with tacrolimus (basal dose 0.1 mg/Kg/day) and mycophenolate mofetil (MMF, basal dose 2g/day) within the first 12 hours after skin closure.

Patients will be randomized in one of the following groups at day 28th post-transplant:

MMF group (n=20): tacrolimus (levels 8-10ng/ml) and MMF (levels 1-3ng/mL).
EVL group (n=20): tacrolimus (levels 8-10ng/ml) and everolimus (levels 2- 4 ng/mL).

HCV monitorization:

HVC-RNA detection and quantification. Serum samples will be taken immediately before liver transplantation, in the anhepatic phase, at the beginning and at the end of the reperfusion, and at 1h, 4h, 8h, 12h, 18h, 1d, 3d, 7d, 14d, 28d, 2m, 3m, 6m, 9m and 12m. Blood samples will be taken from the peripheral circulation and centrifugated within 2 to 3 hours after extraction, aliquoted, and frozen at -80 ºC. The concentration of HCV-RNA will be determined by using a quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay (Cobas Ampliprep/Cobas TaqMan; Roche Molecular Diagnostics, Barcelona, Spain) that achieves a sensitivity of 15 UI/mL and ultra deep pyrosequencing (UDSP) protocols will be used to study DNA genomic factor and viral RNA variability.
Serum fibrosis markers. Serum samples will be taken at 3rd, 6th and 12th months post-transplant from peripheral circulation and frozen at -21ºC. Serum markers (HA, PIIINP, and TIMP-1) will be analyzed by a fully automated, two-site sandwich immunoassay using direct chemiluminometric technology (ADVIA Centayr XP, Siemens Healthcare Diagnositics). The algorithm including the three markers (3-M-ALG) {score= -7,412 + [ln (HA)x0,681] + [ln (PIIINP)x0.775] + [ln (TIMP-1)]x0,494} will be also obtained.
Transient elastography (FibroScan). Liver stiffness measurements using Fibroscan (Echosens, Paris, France) will be performed in clinics at 6th and 12th months post-transplant.
Liver biopsy. Liver biopsy will be performed at 12th months post-transplant. All biopsy specimens will be read by a single pathologist. Necroinflammatory activity and fibrosis stage will be scored using ISHAK classification.

Follow-up and clinical data:

After discharge, patients will be visited in the outpatient clinic monthly for the first 3 months and every 3 months thereafter during the first 12 months post-transplant, at which time clinical and analytical variables will be recorded.Baseline characteristics, HCV genotype and viral load before transplant, surgical variables (type of liver transplant, donor age and steatosis, ischemia time), post-transplantation information and follow-up will be prospectively collected in an electronic database.

Patient withdrawal:

No consent form given by the patient
Severe adverse events related to immunosuppressors used
Steroids are required for long period of time
Antiviral therapy given before during the first year post-transplant
Lost follow-up
Patient death

Conditions: Hepatitis C Recurrence After Liver Transplant
Being tested: EVL arm, MMF arm
Keywords: Hepatitis C, Liver Fibrosis, m-TOR inhibitors
Medical subject headings: Hepatitis C, Liver Cirrhosis

What participants receive

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

EVL armDrug
Also called Everolimus
Patients will be randomized at day 28th post-transplant. This group will receive Tacrolimus+Everolimus.
MMF armDrug
Also called Mofetil Mycophenolate
Patients will be randomized at day 28th post-transplant. This group will continue of current immunosuppressive regimen (Tacrolimus+MMF) / no everolimus introduction.

Study groups in NCT01707849
Study group	Role	What they receive
MMF arm	Active comparator	MMF arm (n=20) They will receive immunosuppression as stipulated by hospital protocol: Tacrolimus (levels 8-10ng/mL) and Mycophenalate mofetil 1mg bid(levels 1-3ng/mL). Receives: Drug: MMF arm
EVL arm	Experimental	EVL arm (n=20): Tacrolimus (levels 8-10ng/ml) + everolimus 1mg bid (levels 2-4 ng/mL) Receives: Drug: EVL arm

What is being measured

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

To compare the liver fibrosis progression (F≥2 under ISHAK score) in patients who receive everolimus vs mTOR free immunosuppression
Liver biopsy will be performed at 12th months post-transplant. All biopsy specimens will be read by a single pathologist. Necroinflammatory activity and fibrosis stage were scored using ISHAK classification.
Measured: One year

Secondary outcomes (1)

To identify viral and recipient molecular predictors of fibrosis and anti-HCV treatment responses in liver transplant recipients under steroid-free immunosuppression
Serum samples from the recipient will be taken immediately before liver transplantation, in the anhepatic phase, at the beginning and at the end of the reperfusion, and at 1h, 4h, 8h, 12h, 18h, 1d, 3d, 7d, 14d, 28d, 2m, 3m, 6m, 9m and 12m. Blood samples will be taken from the peripheral circulation and centrifugated within 2 to 3 hours after extraction, aliquoted, and frozen at -80 ºC.
- The concentration of HCV-RNA will be determined by using a quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay (Cobas Ampliprep/Cobas TaqMan; Roche Molecular Diagnostics, Barcelona, Spain) that achieves a sensitivity of 15 UI/mL. -
- DNA will be extracted from the liver donor and the recipient to characterize DNA polymorphisms. RNA Viral population complexity and presence of resistant mutations will be also studied using ultra-deep pyrosequence using eithre GS-Junior or GS-FLX platforms
Measured: Immediately before liver transplantation, in the anhepatic phase, at the beginning and at the end of the reperfusion, and at 1h, 4h, 8h, 12h, 18h, 1dy, 3dy, 7dy, 14dy, 28dy, 2mo, 3mo, 6mo, 9mo and 12mo post-transplant

Timeline

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

Oct 2012Aug 2016

First posted16 Oct 2012 (estimated)
Study startOct 2012
Primary completionAug 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (23)Papers the sponsor has linked to this study.
Other trials for Hepatitis C Recurrence After Liver TransplantStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 3
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01707849
Sponsor's protocol ID: EVL-VHC-HVH.12
Status last verified: Aug 2016
First submitted: 13 Oct 2012
Last updated: 7 Feb 2018
Results posted: No
Data monitoring committee: Yes
Individual data sharing: No

Publications

Biecker E, De Gottardi A, Neef M, Unternahrer M, Schneider V, Ledermann M, Sagesser H, Shaw S, Reichen J. Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis: analysis of the underlying mechanisms. J Pharmacol Exp Ther. 2005 Jun;313(3):952-61. doi: 10.1124/jpet.104.079616. Epub 2005 Mar 15.
PubMed 15769867
Neef M, Ledermann M, Saegesser H, Schneider V, Reichen J. Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis. J Hepatol. 2006 Dec;45(6):786-96. doi: 10.1016/j.jhep.2006.07.030. Epub 2006 Sep 22.
PubMed 17050028
Patsenker E, Schneider V, Ledermann M, Saegesser H, Dorn C, Hellerbrand C, Stickel F. Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. J Hepatol. 2011 Aug;55(2):388-98. doi: 10.1016/j.jhep.2010.10.044. Epub 2010 Dec 17.
PubMed 21168455
Bilbao I, Sapisochin G, Dopazo C, Lazaro JL, Pou L, Castells L, Caralt M, Blanco L, Gantxegi A, Margarit C, Charco R. Indications and management of everolimus after liver transplantation. Transplant Proc. 2009 Jul-Aug;41(6):2172-6. doi: 10.1016/j.transproceed.2009.06.087.
PubMed 19715864
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
McKenna GJ, Trotter JF, Klintmalm E, Onaca N, Ruiz R, Jennings LW, Neri M, O'Leary JG, Davis GL, Levy MF, Goldstein RM, Klintmalm GB. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression. Am J Transplant. 2011 Nov;11(11):2379-87. doi: 10.1111/j.1600-6143.2011.03767.x. Epub 2011 Oct 3.
PubMed 21967703
Carrion JA, Torres F, Crespo G, Miquel R, Garcia-Valdecasas JC, Navasa M, Forns X. Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation. Hepatology. 2010 Jan;51(1):23-34. doi: 10.1002/hep.23240.
PubMed 19839063
Pungpapong S, Nunes DP, Krishna M, Nakhleh R, Chambers K, Ghabril M, Dickson RC, Hughes CB, Steers J, Nguyen JH, Keaveny AP. Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C. Liver Transpl. 2008 Sep;14(9):1294-302. doi: 10.1002/lt.21508.
PubMed 18756457
Nobili V, Parkes J, Bottazzo G, Marcellini M, Cross R, Newman D, Vizzutti F, Pinzani M, Rosenberg WM. Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease. Gastroenterology. 2009 Jan;136(1):160-7. doi: 10.1053/j.gastro.2008.09.013. Epub 2008 Sep 20.
PubMed 18992746
Carrion JA, Fernandez-Varo G, Bruguera M, Garcia-Pagan JC, Garcia-Valdecasas JC, Perez-Del-Pulgar S, Forns X, Jimenez W, Navasa M. Serum fibrosis markers identify patients with mild and progressive hepatitis C recurrence after liver transplantation. Gastroenterology. 2010 Jan;138(1):147-58.e1. doi: 10.1053/j.gastro.2009.09.047. Epub 2009 Sep 26.
PubMed 19786026
Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, Rimola A, Rodes J. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology. 2002 Mar;35(3):680-7. doi: 10.1053/jhep.2002.31773.
PubMed 11870384
Domingo E, Gomez J. Quasispecies and its impact on viral hepatitis. Virus Res. 2007 Aug;127(2):131-50. doi: 10.1016/j.virusres.2007.02.001. Epub 2007 Mar 8.
PubMed 17349710
Martell M, Esteban JI, Quer J, Genesca J, Weiner A, Esteban R, Guardia J, Gomez J. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol. 1992 May;66(5):3225-9. doi: 10.1128/JVI.66.5.3225-3229.1992.
PubMed 1313927
Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature. 2006 Jan 19;439(7074):344-8. doi: 10.1038/nature04388. Epub 2005 Dec 4.
PubMed 16327776
Forns X, Purcell RH, Bukh J. Quasispecies in viral persistence and pathogenesis of hepatitis C virus. Trends Microbiol. 1999 Oct;7(10):402-10. doi: 10.1016/s0966-842x(99)01590-5.
PubMed 10498948

Study at a glance

From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Unicenter, Prospective, Randomized, Pilot Study Comparing the Effect of Everolimus-containing Versus mTOR Inhibitor Free Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation.
ClinicalTrials.gov ID: NCT01707849
Acronym / sponsor ID: EVL-VHC-HVH.12
Conditions: Hepatitis C Recurrence After Liver Transplant
Keywords: Hepatitis C, Liver Fibrosis, m-TOR inhibitors
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Hospital Vall d'HebronUniversity, hospital or other
Study start: Oct 2012
Primary completion: Aug 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 16 Oct 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Hypothesis:

Use of individualized immunosuppressive regimen and early personalized anti-viral treatment based on recipient and viral factors would improve outcome of HCV infected liver transplant recipients.

Objectives:

To evaluate safety and efficacy of two steroid-free immunosuppressive regimens to reduce hepatitis C recurrence associated to fibrosis progression (F≥2 under ISHAK score) at one year post-transplant.
To identify viral and recipient factors associated with liver fibrosis progression using ultra-deep pyrosequencing (UDPS).

Detailed description

Study design:

A pilot, open-label, prospective, randomized and unicenter study. As pilot study, the number of patients expected to be included is n=40.

Inclusion criteria:

Age≥18 years
First liver transplant
RNA-HCV positive within 12 months previous to the transplant

Exclusion criteria:

Multiorgan transplant
Split liver
ABO incompatible
HIV positive patients
Glomerular Filtration rate ≤60mL/min/1.73m2

Patients will be randomized in one of the following groups at day 28th post-transplant:

MMF group (n=20): tacrolimus (levels 8-10ng/ml) and MMF (levels 1-3ng/mL).
EVL group (n=20): tacrolimus (levels 8-10ng/ml) and everolimus (levels 2- 4 ng/mL).

HCV monitorization:

HVC-RNA detection and quantification. Serum samples will be taken immediately before liver transplantation, in the anhepatic phase, at the beginning and at the end of the reperfusion, and at 1h, 4h, 8h, 12h, 18h, 1d, 3d, 7d, 14d, 28d, 2m, 3m, 6m, 9m and 12m. Blood samples will be taken from the peripheral circulation and centrifugated within 2 to 3 hours after extraction, aliquoted, and frozen at -80 ºC. The concentration of HCV-RNA will be determined by using a quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay (Cobas Ampliprep/Cobas TaqMan; Roche Molecular Diagnostics, Barcelona, Spain) that achieves a sensitivity of 15 UI/mL and ultra deep pyrosequencing (UDSP) protocols will be used to study DNA genomic factor and viral RNA variability.
Serum fibrosis markers. Serum samples will be taken at 3rd, 6th and 12th months post-transplant from peripheral circulation and frozen at -21ºC. Serum markers (HA, PIIINP, and TIMP-1) will be analyzed by a fully automated, two-site sandwich immunoassay using direct chemiluminometric technology (ADVIA Centayr XP, Siemens Healthcare Diagnositics). The algorithm including the three markers (3-M-ALG) {score= -7,412 + [ln (HA)x0,681] + [ln (PIIINP)x0.775] + [ln (TIMP-1)]x0,494} will be also obtained.
Transient elastography (FibroScan). Liver stiffness measurements using Fibroscan (Echosens, Paris, France) will be performed in clinics at 6th and 12th months post-transplant.
Liver biopsy. Liver biopsy will be performed at 12th months post-transplant. All biopsy specimens will be read by a single pathologist. Necroinflammatory activity and fibrosis stage will be scored using ISHAK classification.

Follow-up and clinical data:

Patient withdrawal:

No consent form given by the patient
Severe adverse events related to immunosuppressors used
Steroids are required for long period of time
Antiviral therapy given before during the first year post-transplant
Lost follow-up
Patient death

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
MMF arm	Active comparator	Drug: MMF armMMF arm (n=20) They will receive immunosuppression as stipulated by hospital protocol: Tacrolimus (levels 8-10ng/mL) and Mycophenalate mofetil 1mg bid(levels 1-3ng/mL).
EVL arm	Experimental	Drug: EVL armEVL arm (n=20): Tacrolimus (levels 8-10ng/ml) + everolimus 1mg bid (levels 2-4 ng/mL)

Who may qualify

Ages: 18 to 68 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Age≥18 years
First liver transplant
RNA-HCV positive within 12 months previous to the transplant

Key exclusion criteria (6 listed)

Multiorgan transplant
Split liver
Fulminant hepatitis
ABO incompatible
HIV positive patients

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EVL armAlso: EverolimusPatients will be randomized at day 28th post-transplant. This group will receive Tacrolimus+Everolimus.	Drug	EVL arm
MMF armAlso: Mofetil MycophenolatePatients will be randomized at day 28th post-transplant. This group will continue of current immunosuppressive regimen (Tacrolimus+MMF) / no everolimus introduction.	Drug	MMF arm

Primary outcome

To compare the liver fibrosis progression (F≥2 under ISHAK score) in patients who receive everolimus vs mTOR free immunosuppression
Time frame: One year
Liver biopsy will be performed at 12th months post-transplant. All biopsy specimens will be read by a single pathologist. Necroinflammatory activity and fibrosis stage were scored using ISHAK classification.

1 secondary outcome

To identify viral and recipient molecular predictors of fibrosis and anti-HCV treatment responses in liver transplant recipients under steroid-free immunosuppression
Time frame: Immediately before liver transplantation, in the anhepatic phase, at the beginning and at the end of the reperfusion, and at 1h, 4h, 8h, 12h, 18h, 1dy, 3dy, 7dy, 14dy, 28dy, 2mo, 3mo, 6mo, 9mo and 12mo post-transplant

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
Background: PubMed 15769867Biecker E, De Gottardi A, Neef M, Unternahrer M, Schneider V, Ledermann M, Sagesser H, Shaw S, Reichen J. Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis: analysis of the underlying mechanisms. J Pharmacol Exp Ther. 2005 Jun;313(3):952-61. doi: 10.1124/jpet.104.079616. Epub 2005 Mar 15.
Background: PubMed 17050028Neef M, Ledermann M, Saegesser H, Schneider V, Reichen J. Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis. J Hepatol. 2006 Dec;45(6):786-96. doi: 10.1016/j.jhep.2006.07.030. Epub 2006 Sep 22.
Background: PubMed 21168455Patsenker E, Schneider V, Ledermann M, Saegesser H, Dorn C, Hellerbrand C, Stickel F. Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. J Hepatol. 2011 Aug;55(2):388-98. doi: 10.1016/j.jhep.2010.10.044. Epub 2010 Dec 17.
Background: PubMed 19715864Bilbao I, Sapisochin G, Dopazo C, Lazaro JL, Pou L, Castells L, Caralt M, Blanco L, Gantxegi A, Margarit C, Charco R. Indications and management of everolimus after liver transplantation. Transplant Proc. 2009 Jul-Aug;41(6):2172-6. doi: 10.1016/j.transproceed.2009.06.087.
Background: PubMed 20483386Wagner 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.
Background: PubMed 21967703McKenna GJ, Trotter JF, Klintmalm E, Onaca N, Ruiz R, Jennings LW, Neri M, O'Leary JG, Davis GL, Levy MF, Goldstein RM, Klintmalm GB. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression. Am J Transplant. 2011 Nov;11(11):2379-87. doi: 10.1111/j.1600-6143.2011.03767.x. Epub 2011 Oct 3.
Background: PubMed 19839063Carrion JA, Torres F, Crespo G, Miquel R, Garcia-Valdecasas JC, Navasa M, Forns X. Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation. Hepatology. 2010 Jan;51(1):23-34. doi: 10.1002/hep.23240.
Background: PubMed 18756457Pungpapong S, Nunes DP, Krishna M, Nakhleh R, Chambers K, Ghabril M, Dickson RC, Hughes CB, Steers J, Nguyen JH, Keaveny AP. Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C. Liver Transpl. 2008 Sep;14(9):1294-302. doi: 10.1002/lt.21508.
Background: PubMed 18992746Nobili V, Parkes J, Bottazzo G, Marcellini M, Cross R, Newman D, Vizzutti F, Pinzani M, Rosenberg WM. Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease. Gastroenterology. 2009 Jan;136(1):160-7. doi: 10.1053/j.gastro.2008.09.013. Epub 2008 Sep 20.
Background: PubMed 19786026Carrion JA, Fernandez-Varo G, Bruguera M, Garcia-Pagan JC, Garcia-Valdecasas JC, Perez-Del-Pulgar S, Forns X, Jimenez W, Navasa M. Serum fibrosis markers identify patients with mild and progressive hepatitis C recurrence after liver transplantation. Gastroenterology. 2010 Jan;138(1):147-58.e1. doi: 10.1053/j.gastro.2009.09.047. Epub 2009 Sep 26.
Background: PubMed 11870384Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, Rimola A, Rodes J. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology. 2002 Mar;35(3):680-7. doi: 10.1053/jhep.2002.31773.
Background: PubMed 17349710Domingo E, Gomez J. Quasispecies and its impact on viral hepatitis. Virus Res. 2007 Aug;127(2):131-50. doi: 10.1016/j.virusres.2007.02.001. Epub 2007 Mar 8.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Itxarone Bilbao, PhD/MD principal investigator

Department of HPB Surgery and Transplant, Hospital Vall d´Hebron (Barcelona, Spain)

Ramon Charco, PhD/MD study director

Department of HPB and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

Josep Quer, PhD/MD study chair

Hepatology Unit, Department of Internal Medicine, Hospital Vall d´Hebron, CIBERehd, Barcelona (Spain)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing EVL arm and MMF arm in people with Hepatitis C Recurrence After Liver Transplant, run by Hospital Vall d'Hebron at 1 site in Spain.

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 3 inclusion and 6 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 7 Feb 2018. 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 Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

To compare the liver fibrosis progression (F≥2 under ISHAK score) in patients who receive everolimus vs mTOR free immunosuppression (time frame: One year). 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 NCT01707849, which also lists 23 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 7 Feb 2018.