Hepatitis CPhase 4NCT00167557
Orthotopic Liver Transplant (OLT) Recipients With Hepatitis C Virus (HCV) Under Preemptive Treatment
A Phase 4 study testing Pegylated Interferon, Ribavirin and Liver Biopsy in people with Hepatitis C, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
After a liver transplant, the hepatitis C virus (which destroyed one's own liver) eventually comes back. In many patients, this will eventually cause the loss of the new liver and can also confuse the doctors taking care of them because it is hard to tell the difference between one's body rejecting the new liver and… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Pegylated Interferon, Ribavirin and Liver Biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Mar 2008
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female patients between 18 and 70 years of age
- All liver transplant patients with a positive HCV RNA by PCR within 30 days after transplant.
- No evidence of acute or chronic rejection within 4 weeks of enrollment
- Compensated liver disease according to the following criteria:
- Hemoglobin > 10 gm/dL;
- Neutrophil count > 1,000/mm3;
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- Platelet count > 50,000/mm3;
- Serum creatinine < 2.0 mg/dL.
- Documentation of adequate contraception in females and males sexually active or of childbearing potential.
Who cannot join
- Hypersensitivity to alpha interferon and/or ribavirin
- Previous treatment with interferon and/or ribavirin post liver transplantation
- HIV
- Autoimmune hepatitis
- Active alcohol or substance abuse
- Non compliance
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- Hemoglobinopathies or hemolytic anemia
- Clinical significant retinal abnormalities
- Decompensated cardio-vascular, endocrine, pulmonary, renal, immune, metabolic, dermatologic or psychiatric illness
- Re-transplantation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Tacrolimus Monotherapy in OLT Recipients With HCV Under Preemptive Treatment With Interferon and Ribavirin
After a liver transplant, the hepatitis C virus (which destroyed one's own liver) eventually comes back. In many patients, this will eventually cause the loss of the new liver and can also confuse the doctors taking care of them because it is hard to tell the difference between one's body rejecting the new liver and hepatitis. This can cause serious treatment errors that can lead to more severe hepatitis or to rejection of the liver. Some of the drugs used to prevent rejection of one's new liver can cause the hepatitis to come back in a more severe form. This is especially true for the drugs known as corticosteroids.
Right now, the only effective treatment against hepatitis C is a combination of two drugs called interferon and ribavirin. These drugs act by strengthening one's immune system to fight the virus and by directly reducing the reproduction of the virus. Because the treatment with these drugs is associated with many side effects, there is little experience with treating patients after liver transplantation with them.
Read more
In the investigators' transplant program, they have decided to treat all patients with hepatitis C as early as possible after transplantation and to follow them closely for the development of hepatitis and side effects of the treatment. The investigators treat one's hepatitis as early as possible, before any actual damage has occurred in the new liver. This approach has been tried before but it has been hard to tell if it has worked or not. The main reason for failure was that many patients could not complete the treatment due to side effects. The investigators' purpose is to treat those side effects aggressively so that most patients can complete the treatment course.
The purpose of this study is to collect all the data regarding the investigators' treatment protocol so that they will be able to learn if this form of treatment is beneficial.
The study includes performing liver biopsies at scheduled times after one's liver transplant and for scheduled blood tests to see how much virus is still in the blood. If patients show signs that they are not responding to treatment they will be removed from the study.
Read the detailed description
HCV recurs in the transplanted liver almost invariably. The clinical course is variable and ranges from no hepatitis to severe aggressive hepatitis with cirrhosis. Factors that affect outcome are high viral load prior to OLT, genotype, and immunosuppressive regimen. Recent studies indicate that the severity of recurrence is increasing with longer follow up, and longevity of both graft and patient is compromised by HCV. Viral load appears to be particularly affected by corticosteroids. The impact of mycophenolate mofetil and tacrolimus is not certain. The results of re-transplantation are generally poor and seem to be a non-cost beneficial way to deal with recurrence HCV cirrhosis. Additionally, re-transplantation deprives other patients from getting OLT in a timely fashion.
Recent studies have shown that with intensive alpha interferon and ribavirin treatment, up to 40% of patients can be cleared of virus as measured by PCR. Thus, despite the cost and side effects of this treatment, it appears justified to treat recurrence preemptively.
Due to the deleterious effects of high dose Corticosteroids it seems logical to attempt to withdraw them as soon as possible from treatment. MMF is often incompatible with interferon and ribavirin treatment due to leukopenia and anemia. The same is true for sirolimus. Thus, most patients will eventually be treated with Tacrolimus monotherapy. Presently, numerous patients end up being treated with Tacrolimus monotherapy as part of the reduction in immune suppression, which occurs over time. There is, however, very little prospective data regarding Tacrolimus monotherapy and almost no data on the specific issue of monotherapy in HCV patients. Even less is known with respect to this type of treatment while using interferon and ribavirin.
Our purpose in this protocol is to examine both the effect of preemptive antiviral treatment on recurrent HCV and the effect of Tacrolimus monotherapy in this setting. This may be important as more and more programs are turning to preemptive anti viral treatment and the issue of appropriate immune suppression becomes seminal to this discussion.
Aims
- To determine the safety and efficacy of PEG interferon and ribavirin in the treatment of HCV recurrence after OLT.
- To determine the effectiveness and safety of maintenance dose of PEG interferon to delay progression of fibrosis and histologic damage, in non-responders to the initial regimen of PEG interferon and ribavirin.
- To determine the effect of early prednisone withdrawal in the rate of response to treatment with PEG interferon and ribavirin.
- To assess the feasibility of Tacrolimus monotherapy in patients undergoing treatment for HCV recurrence post transplant.
- Conditions
- Hepatitis C
- Being tested
- Pegylated Interferon, Ribavirin, Liver Biopsy
- Keywords
- Liver Transplantation
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pegylated InterferonDrug
180mcg SC weekly starting 30 days post transplant
RibavirinDrug
goal dose 13mg/kg starting 120 days post transplant for a minimum of 48 wks
Liver BiopsyProcedure or surgery
Liver biopsies performed at 9 points in time from time of liver transplant
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Study | Experimental | Not described Receives: Drug: Pegylated Interferon; Drug: Ribavirin; Procedure: Liver Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral clearance after liver transplantation
Measured: 3 yrs. post liver transplant
Secondary outcomes (2)
histological progression of fibrosis and inflammation
Measured: 3 yrs. post liver transplant
rate of rejection on HCV treatment
Measured: 3 yrs post liver transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startJan 2005
- Primary completionMar 2008
- Study completionMar 2008
Why it stopped: The PI left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Responsible party
- Sponsor
- Investigators
- Hadar J Merhav, MD, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167557
- Sponsor's protocol ID
- HSC-MS-04-0346
- Other IDs
- Astellas Pharma, FHIprojectno.JK-04-002
- Status last verified
- Nov 2013
- First submitted
- 9 Sep 2005
- Last updated
- 19 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tacrolimus Monotherapy in OLT Recipients With HCV Under Preemptive Treatment With Interferon and Ribavirin
- ClinicalTrials.gov ID
- NCT00167557
- Acronym / sponsor ID
- HSC-MS-04-0346
- Conditions
- Hepatitis C
- Keywords
- Liver Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The PI left the institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Study start
- Jan 2005
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 14 Sep 2005 (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.
After a liver transplant, the hepatitis C virus (which destroyed one's own liver) eventually comes back. In many patients, this will eventually cause the loss of the new liver and can also confuse the doctors taking care of them because it is hard to tell the difference between one's body rejecting the new liver and hepatitis. This can cause serious treatment errors that can lead to more severe hepatitis or to rejection of the liver. Some of the drugs used to prevent rejection of one's new liver can cause the hepatitis to come back in a more severe form. This is especially true for the drugs known as corticosteroids.
Right now, the only effective treatment against hepatitis C is a combination of two drugs called interferon and ribavirin. These drugs act by strengthening one's immune system to fight the virus and by directly reducing the reproduction of the virus. Because the treatment with these drugs is associated with many side effects, there is little experience with treating patients after liver transplantation with them.
In the investigators' transplant program, they have decided to treat all patients with hepatitis C as early as possible after transplantation and to follow them closely for the development of hepatitis and side effects of the treatment. The investigators treat one's hepatitis as early as possible, before any actual damage has occurred in the new liver. This approach has been tried before but it has been hard to tell if it has worked or not. The main reason for failure was that many patients could not complete the treatment due to side effects. The investigators' purpose is to treat those side effects aggressively so that most patients can complete the treatment course.
The purpose of this study is to collect all the data regarding the investigators' treatment protocol so that they will be able to learn if this form of treatment is beneficial.
The study includes performing liver biopsies at scheduled times after one's liver transplant and for scheduled blood tests to see how much virus is still in the blood. If patients show signs that they are not responding to treatment they will be removed from the study.
Detailed description
HCV recurs in the transplanted liver almost invariably. The clinical course is variable and ranges from no hepatitis to severe aggressive hepatitis with cirrhosis. Factors that affect outcome are high viral load prior to OLT, genotype, and immunosuppressive regimen. Recent studies indicate that the severity of recurrence is increasing with longer follow up, and longevity of both graft and patient is compromised by HCV. Viral load appears to be particularly affected by corticosteroids. The impact of mycophenolate mofetil and tacrolimus is not certain. The results of re-transplantation are generally poor and seem to be a non-cost beneficial way to deal with recurrence HCV cirrhosis. Additionally, re-transplantation deprives other patients from getting OLT in a timely fashion.
Recent studies have shown that with intensive alpha interferon and ribavirin treatment, up to 40% of patients can be cleared of virus as measured by PCR. Thus, despite the cost and side effects of this treatment, it appears justified to treat recurrence preemptively.
Due to the deleterious effects of high dose Corticosteroids it seems logical to attempt to withdraw them as soon as possible from treatment. MMF is often incompatible with interferon and ribavirin treatment due to leukopenia and anemia. The same is true for sirolimus. Thus, most patients will eventually be treated with Tacrolimus monotherapy. Presently, numerous patients end up being treated with Tacrolimus monotherapy as part of the reduction in immune suppression, which occurs over time. There is, however, very little prospective data regarding Tacrolimus monotherapy and almost no data on the specific issue of monotherapy in HCV patients. Even less is known with respect to this type of treatment while using interferon and ribavirin.
Our purpose in this protocol is to examine both the effect of preemptive antiviral treatment on recurrent HCV and the effect of Tacrolimus monotherapy in this setting. This may be important as more and more programs are turning to preemptive anti viral treatment and the issue of appropriate immune suppression becomes seminal to this discussion.
Aims
- To determine the safety and efficacy of PEG interferon and ribavirin in the treatment of HCV recurrence after OLT.
- To determine the effectiveness and safety of maintenance dose of PEG interferon to delay progression of fibrosis and histologic damage, in non-responders to the initial regimen of PEG interferon and ribavirin.
- To determine the effect of early prednisone withdrawal in the rate of response to treatment with PEG interferon and ribavirin.
- To assess the feasibility of Tacrolimus monotherapy in patients undergoing treatment for HCV recurrence post transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm Study | Experimental | Drug: Pegylated Interferon, Drug: Ribavirin, Procedure: Liver Biopsy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adult male or female patients between 18 and 70 years of age
- All liver transplant patients with a positive HCV RNA by PCR within 30 days after transplant.
- No evidence of acute or chronic rejection within 4 weeks of enrollment
- Compensated liver disease according to the following criteria:
- Documentation of adequate contraception in females and males sexually active or of childbearing potential.
Key exclusion criteria (10 listed)
- Hypersensitivity to alpha interferon and/or ribavirin
- Previous treatment with interferon and/or ribavirin post liver transplantation
- HIV
- Autoimmune hepatitis
- Active alcohol or substance abuse
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 |
|---|---|---|
| Pegylated Interferon180mcg SC weekly starting 30 days post transplant | Drug | Single Arm Study |
| Ribaviringoal dose 13mg/kg starting 120 days post transplant for a minimum of 48 wks | Drug | Single Arm Study |
| Liver BiopsyLiver biopsies performed at 9 points in time from time of liver transplant | Procedure or surgery | Single Arm Study |
Primary outcome
Viral clearance after liver transplantation
Time frame: 3 yrs. post liver transplant
2 secondary outcomes
histological progression of fibrosis and inflammation
Time frame: 3 yrs. post liver transplant
rate of rejection on HCV treatment
Time frame: 3 yrs post liver transplant
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2013.
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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.
Hadar J Merhav, MD principal investigator
The University of Texas Health Science Center, Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pegylated Interferon, Ribavirin and Liver Biopsy in people with Hepatitis C, run by The University of Texas Health Science Center, Houston at 1 site in United States.
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 9 inclusion and 10 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: withdrawn, as of the sponsor's last update on 19 Nov 2013. 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 United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
Viral clearance after liver transplantation (time frame: 3 yrs. post liver transplant). 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 19 Nov 2013.