Hepatitis CPhase 4SUSTAINNCT00938860
Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
A Phase 4 study testing cyclosporin (Neoral) and tacrolimus (Prograf) in people with Hepatitis C and Liver Transplantation, run by Novartis Pharmaceuticals at 45 sites in 13 countries.
Trial summary
This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C, Liver Transplantation
- What is being tested?
- cyclosporin (Neoral) and tacrolimus (Prograf)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 45 sitesin 13 countries
- Study dates
- Sep 2009to May 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Liver transplantation performed at least 6 months and up to 5 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
- Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at least 6 months prior randomization
- Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at screening
- Indication of treatment with Peg-IFN and ribavirin due to histological evidence of chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to 4 months prior to randomization.
Who cannot join
- Serum creatinine >150 μmol/L (1.6 7 mg/dL) or eGFR < 50 ml/min (4-variable Modification of Diet in Renal Disease [MDRD Cockcroft-Gault formula])
- Multi-organ transplant recipients
- Recent episode of steroid-treated acute rejection (AR) within 3 months prior to randomization, or >1 episode of steroid-treated AR in the last 6 months, or any number of steroid-resistant AR episodes in the last 6 months including evidence of chronic rejection or ductopenia
- Evidence of conditions that could cause graft dysfunction other than HCV infection
- Patients with signs of decompensated liver disease, defined as presence of ascites, variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin <3.5g/dL or, total direct bilirubin >1.5mg/dL or, INR >1.5)
- Co-infection with HIV or Hepatitis B (defined as HBsAg-positive) at screening
Show all 13Show fewer
- Use of mTOR inhibitors (everolimus or sirolimus) in the 6 months prior to screening
- Antiviral treatment for HCV administered at any time after liver transplantation
- Patients on daily doses of corticosteroids higher than 5 mg/day
- Patients with fibrosing cholestatic hepatitis
- Patients with current diagnosis of malignancies, including lymphoproliferative disorders
- Patients with platelet count <70,000/mm3 or neutrophiles <1,500/mm3
- History of HCC outside Milan criteria based on radiology or UCSF criteria based on analysis of the explant
Trial locations and contacts
45 sites in 13 countries.
45 sites in 13 countries
United States9 sites
Novartis Investigative Site
Chapel Hill, North Carolina, 27599-7211
Novartis Investigative Site
Gainesville, Florida, 32610
Novartis Investigative Site
Houston, Texas, 77030-2400
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Madison, Wisconsin, 53792
Novartis Investigative Site
Oklahoma City, Oklahoma, 73112
Novartis Investigative Site
Palo Alto, California, 95128
Novartis Investigative Site
Phoenix, Arizona, 85054
Novartis Investigative Site
San Francisco, California, 94143-2205
France6 sites
Novartis Investigative Site
Créteil, 94000
Novartis Investigative Site
Lyon, 69317
Novartis Investigative Site
Montpellier, 34295
Novartis Investigative Site
Paris, 75012
Novartis Investigative Site
Toulouse, 31054
Novartis Investigative Site
Villejuif, 94800
Canada5 sites
Novartis Investigative Site
Edmonton, Alberta, T6G 2B7
Novartis Investigative Site
London, Ontario, N6A 4G5
Novartis Investigative Site
Toronto, Ontario, M5G 2C4
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1M9
Novartis Investigative Site
Winnipeg, Manitoba, R3E 0W3
Spain5 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Oviedo, Principality of Asturias, 33006
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
Novartis Investigative Site
Valladolid, Castille and León, 47012
Germany4 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
München, 81377
South Korea4 sites
Novartis Investigative Site
Seoul, Korea, 110 744
Novartis Investigative Site
Seoul, Korea, 120-752
Novartis Investigative Site
Seoul, Korea, 135-710
Novartis Investigative Site
Seoul, Korea, 137-701
Italy3 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Udine, UD, 33100
Brazil2 sites
Novartis Investigative Site
Fortaleza, Ceará, 60430-270
Novartis Investigative Site
São Paulo, São Paulo, 04023-900
Colombia2 sites
Novartis Investigative Site
Bogotá, Cundinamarca, 110111
Novartis Investigative Site
Bogotá
Russia2 sites
Novartis Investigative Site
Moscow, 123182
Novartis Investigative Site
Moscow, 129010
About this study
Official title: A Multi-center, Randomized, Open Label, Controlled Study to Compare the Sustained Virological Response During Treatment With Neoral or Tacrolimus in Maintenance Liver Transplant Recipients Treated With Pegylated Interferon and Ribavirin for Recurrent Hepatitis C
This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.
- Conditions
- Hepatitis C, Liver Transplantation
- Being tested
- cyclosporin (Neoral), tacrolimus (Prograf)
- Keywords
- Hepatitis C, liver transplantation, anti-viral therapy
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporin (Neoral)Drug
Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
tacrolimus (Prograf)Drug
Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.
| Study group | Role | What they receive |
|---|---|---|
| Neoral | Experimental | Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges Receives: Drug: cyclosporin (Neoral) |
| tacrolimus | Active comparator | Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges. Receives: Drug: tacrolimus (Prograf) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus
The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Measured: Week 24
Secondary outcomes (8)
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
Efficacy failure (biopsy proven acute rejection (BPAR), graft loss, or death
Measured: Week 80
Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline)
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite, Participants showing an increase of Ishak Knodell fibrosis score by at least one level (increase of ≥1)
Measured: Week 80
Number of Participants of Rapid Viral Response (RVR)
RVR defined as non-detectable HCV RNA 4 weeks after initiation of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Measured: Week 4
Number of Participants of Early Viral Response (EVR)
EVR defined as non-detectable HCV RNA or a ≥2 logs reduction of HCV RNA at 12 weeks after initiation of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Measured: Week 12
Number of Participants for the End of Treatment Response (ETR)
ETR defined as non-detectable HCV RNA at the completion of AV treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Measured: Week 80
Number of Participants of True Non-responder Rate
Defined as failure to achieve at least a 2 log reduction of Hepatitis C virus (HCV) RNA. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Measured: Week 80
Number of Participants for Relapse Rate
Defined as reappearance of detectable Hepatitis C Virus (HCV) RNA at 24 weeks after completion of antiviral treatment when HCV RNA was undetectable at the end of treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Measured: Week 24
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Defined as number of patients with dose reduction or discontinuation of AV therapy due to poor tolerability
Measured: Week 80
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2009 (estimated)
- Study startSep 2009
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00938860
- Sponsor's protocol ID
- COLO400A2430
- Other IDs
- 2009-010806-12, 2009
- Acronym
- SUSTAIN
- Status last verified
- May 2015
- First submitted
- 13 Jul 2009
- Last updated
- 22 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Open Label, Controlled Study to Compare the Sustained Virological Response During Treatment With Neoral or Tacrolimus in Maintenance Liver Transplant Recipients Treated With Pegylated Interferon and Ribavirin for Recurrent Hepatitis C
- ClinicalTrials.gov ID
- NCT00938860
- Acronym / sponsor ID
- SUSTAIN / COLO400A2430
- Conditions
- Hepatitis C, Liver Transplantation
- Keywords
- Hepatitis C, liver transplantation, anti-viral therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 14 Jul 2009 (estimated)
- Results
- Posted 26 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoral | Experimental | Drug: cyclosporin (Neoral)Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges |
| tacrolimus | Active comparator | Drug: tacrolimus (Prograf)Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Liver transplantation performed at least 6 months and up to 5 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
- Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at least 6 months prior randomization
- Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at screening
- Indication of treatment with Peg-IFN and ribavirin due to histological evidence of chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to 4 months prior to randomization.
Key exclusion criteria (13 listed)
- Serum creatinine >150 μmol/L (1.6 7 mg/dL) or eGFR < 50 ml/min (4-variable Modification of Diet in Renal Disease [MDRD Cockcroft-Gault formula])
- Multi-organ transplant recipients
- Recent episode of steroid-treated acute rejection (AR) within 3 months prior to randomization, or >1 episode of steroid-treated AR in the last 6 months, or any number of steroid-resistant AR episodes in the last 6 months including evidence of chronic rejection or ductopenia
- Evidence of conditions that could cause graft dysfunction other than HCV infection
- Patients with signs of decompensated liver disease, defined as presence of ascites, variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin <3.5g/dL or, total direct bilirubin >1.5mg/dL or, INR >1.5)
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 |
|---|---|---|
| cyclosporin (Neoral)Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges | Drug | Neoral |
| tacrolimus (Prograf)Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges. | Drug | tacrolimus |
Primary outcome
Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus
Time frame: Week 24
The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
8 secondary outcomes
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
Time frame: Week 80
Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline)
Time frame: Week 80
Number of Participants of Rapid Viral Response (RVR)
Time frame: Week 4
Number of Participants of Early Viral Response (EVR)
Time frame: Week 12
Number of Participants for the End of Treatment Response (ETR)
Time frame: Week 80
Number of Participants of True Non-responder Rate
Time frame: Week 80
Number of Participants for Relapse Rate
Time frame: Week 24
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Time frame: Week 80
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
45 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cyclosporin (Neoral) and tacrolimus (Prograf) in people with Hepatitis C and Liver Transplantation, run by Novartis Pharmaceuticals at 45 sites in 13 countries.
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 4 inclusion and 13 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 22 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, France, Canada, Spain, Germany and 8 more countries. 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?
Yes. Results are posted in the registry (first posted 26 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2015.