Chronic Hepatitis CPhase 4NCT00001854
Long-Term Therapy With Ribavirin for Chronic Hepatitis C
A Phase 4 study testing Ribavirin in people with Chronic Hepatitis C, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Chronic hepatitis C is a disease of the liver caused by the hepatitis C virus. The disease can be serious and even fatal. Approximately 25% of patients with chronic hepatitis C will develop cirrhosis and some of these patients will develop cancer of the liver or liver failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Ribavirin
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 1999to 15 Jan 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age above 18 years, male or female.
- Elevated alanine (ALT) or asparate (AST) aminotransferase activities averaging at least twice the upper limit of normal on three determinations taken at least one month apart during the previous 6 months. The mean of these three determinations will be defined as "baseline" ALT and AST levels.
- Presence of anti-HCV and HCV RNA in serum tested at least once during the previous six months.
- Evidence of chronic hepatitis on liver biopsy done within the previous 12 months with a histology activity index of at least 6 (out of a maximum of 22).
- Contraindications to the use of alpha interferon, either in the form of specific contraindications to its use (depression, psychiatric illness, neurological impairment, severe thrombocytopenia, autoimmune disease), or the history of severe side effects or intolerance during a previous course of alpha interferon, or lack of a sustained virological (sustained lost of HCV RNA from serum for more than six months after stopping treatment) response to an adequate course (6 months) of the combination of alpha interferon and ribavirin or (after September 1, 2003) the combination of peginterferon and ribavirin.
- Written informed consent.
- An important group of patients who were enrolled in the current study, were patients who participated in the Clinical Research Protocol 98-DK-0003 (Combination of alpha interferon with long-term ribavirin for patients with chronic hepatitis C) and who did not have a sustained virological response to this treatment. These patients were eligible to enroll into the current study once they had finished the therapy and follow up period in that trial. These patients fit the inclusion criteria listed above with one exception: some patients were receiving ribavirin monotherapy as a part of their participation in 98-DK-0003. These patients were eligible to be immediately enrolled into this study without a medication-free period in between.
Who cannot join
- Pregancy or, in women of childbearing potential, inability to practice adequate contraception. Men with spouses or sexual partners of childbearing potential also be excluded if they are unable to practice adequate contraception.
- Significant systemic illnesses other than liver disease, including a history of congestive heart failure, cerebral vascular disease, renal failure (creatinine clearance less than 50 ml/min), and angina pectoris.
- Patients with an abnormal stress test or carotid untrasound will not be enrolled into this study.
- Pre-existing anemia (hematocrit less than 32%) or known history of hemolytic anemia.
- Interferon or immunosuppressive therapy within the last 6 months.
- Evidence of another form of liver disease in addition to viral hepatitis, such as autoimmune or alcoholic liver disease.
- Active or recent (within one year) alcohol or drug abuse or psychiatric illness that is likely to interfere with compliance and requirements for safety monitoring during this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Chronic hepatitis C is a disease of the liver caused by the hepatitis C virus. The disease can be serious and even fatal. Approximately 25% of patients with chronic hepatitis C will develop cirrhosis and some of these patients will develop cancer of the liver or liver failure.
Presently the disease is treated with a combination of alpha interferon or peginterferon (antiviral and immune stimulating drugs) and ribavirin (an antiviral drug). Alpha interferon is given by injection three times a week whereas peginterferon is given by injection only once a week. Ribavirin is given as a tablet by mouth twice a day. The combination therapy is given for 6 to months. About half of the patients given these medications will receive a lasting benefit and many patients do not respond well to the combination therapy.
Read more
This study will select up to 50 patients will chronic hepatitis C who have not responded to combination therapy or who could not stand the side effects associated with interferon or peginterferon therapy. These subjects will be evaluated and undergo liver biopsy to determine their present liver condition. If selected as subjects they will be started on single drug therapy with ribavirin. The drug will be given orally twice a day at a dose based on the patient's body weight.
The patients will be followed on an out-patient basis. They will we asked to return for regular check-ups and blood tests every 2 to 8 weeks for the duration of the study. After 6 months, the medication will be stopped or adjusted based on the results of the subject's blood tests (liver enzymes). A response is considered if a decrease of 50% or more of the initial liver enzyme (alanine aminotransferase, ALT) is noted. A complete response will be considered if liver enzymes return to normal levels.
Therapy will be discontinued after 6 months if patients do not respond. However, patients that respond to the single drug therapy will continue to receive the medication at a decreased dose. The patients will remain on an appropriate dose for up to 8 years with repeat liver biopsies at 2, 4 and 8 years to assess progress.
This study will determine if long-term therapy with ribavirin is safe and effective.
Read the detailed description
Up to 50 patients with chronic hepatitis C will be treated for up to eight years with ribavirin, an orally administered antiviral agent. Patients will be chosen who have moderate to severe chronic hepatitis C who previously failed to have a sustained virological response to the combination of alpha interferon and ribavirin or who were intolerant to interferon therapy or who have significant contraindications to the use of interferon.
After medical evaluation and liver biopsy, patients will begin receiving ribavirin in a dose of 1000 mg (body weight less than 75 K) or 1200 mg daily (two or three capsules of 200 mg twice daily by mouth). Patients will be followed on therapy with visits to the outpatient clinic for medical interview, physical examinations and blood tests at 2 to 8 week intervals. After six months, the dose of ribavirin will be stopped or adjusted based upon changes in alanine aminotransferase (ALT) levels comparing the average of the three values from month 2, 4, and 6 to the baseline levels. A decrease by 50% or more will be considered a partial biomedical response and a decrease to within the normal range will be considered a complete biochemical response. In patients who do not respond by six months, therapy will be stopped, whereas, in patients who respond, therapy will be continued decreasing the dose in increments of 200 mg per day every 6 months as long as a biochemical response is maintained. The minimal dose will be 400 mg per day. In patients with a response, therapy will be continued for up to 8 years with repeat liver biopsies and evaluations at 2, 4 and 8 years.
The primary criterion for success of therapy will be the degree of histologic improvement on liver biopsy at 2, 4 and 8 years; supportive, secondary criteria will be improvements in ALT levels and in symptoms done at the same time points. This open-label pilot study will allow for therapy of patients with resistant forms of chronic hepatitis C and will address whether long-term therapy with this agent is safe, as well as whether prolonged monotherapy with ribavirin leads to sustained improvements in serum ALT levels, whether these can be maintained using lower doses of ribavirin, and whether the improvements reflect amelioration of the underlying liver disease as judged histologically.
- Conditions
- Chronic Hepatitis C
- Being tested
- Ribavirin
- Keywords
- Ribavirin, Liver Disease, Antiviral Agent, Cirrhosis, Chronic Hepatitis, Iron, Viral Hepatitis, Hepatitis C Virus, Hemolytic Anemia, Hemolysis
- Medical subject headings
- Hepatitis C, Chronic, Liver Diseases, Fibrosis, Hepatitis, Chronic, Hepatitis C, Anemia, Hemolytic, Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibavirinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start12 Feb 1999
- Primary completion10 Oct 2007
- Study completion15 Jan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001854
- Sponsor's protocol ID
- 990042
- Other IDs
- 99-DK-0042
- Status last verified
- 15 Jan 2008
- First submitted
- 3 Nov 1999
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Lau DT, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH. 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology. 1998 Oct;28(4):1121-7. doi: 10.1002/hep.510280430.
PubMed 9755252
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-Term Therapy With Ribavirin for Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT00001854
- Acronym / sponsor ID
- 990042
- Conditions
- Chronic Hepatitis C
- Keywords
- Ribavirin, Liver Disease, Antiviral Agent, Cirrhosis, Chronic Hepatitis, Iron, Viral Hepatitis, Hepatitis C Virus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 12 Feb 1999
- Primary completion
- 10 Oct 2007 (actual)
- Study completion
- 15 Jan 2008 (actual)
- First posted
- 4 Nov 1999 (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.
Chronic hepatitis C is a disease of the liver caused by the hepatitis C virus. The disease can be serious and even fatal. Approximately 25% of patients with chronic hepatitis C will develop cirrhosis and some of these patients will develop cancer of the liver or liver failure.
Presently the disease is treated with a combination of alpha interferon or peginterferon (antiviral and immune stimulating drugs) and ribavirin (an antiviral drug). Alpha interferon is given by injection three times a week whereas peginterferon is given by injection only once a week. Ribavirin is given as a tablet by mouth twice a day. The combination therapy is given for 6 to months. About half of the patients given these medications will receive a lasting benefit and many patients do not respond well to the combination therapy.
This study will select up to 50 patients will chronic hepatitis C who have not responded to combination therapy or who could not stand the side effects associated with interferon or peginterferon therapy. These subjects will be evaluated and undergo liver biopsy to determine their present liver condition. If selected as subjects they will be started on single drug therapy with ribavirin. The drug will be given orally twice a day at a dose based on the patient's body weight.
The patients will be followed on an out-patient basis. They will we asked to return for regular check-ups and blood tests every 2 to 8 weeks for the duration of the study. After 6 months, the medication will be stopped or adjusted based on the results of the subject's blood tests (liver enzymes). A response is considered if a decrease of 50% or more of the initial liver enzyme (alanine aminotransferase, ALT) is noted. A complete response will be considered if liver enzymes return to normal levels.
Therapy will be discontinued after 6 months if patients do not respond. However, patients that respond to the single drug therapy will continue to receive the medication at a decreased dose. The patients will remain on an appropriate dose for up to 8 years with repeat liver biopsies at 2, 4 and 8 years to assess progress.
This study will determine if long-term therapy with ribavirin is safe and effective.
Detailed description
Up to 50 patients with chronic hepatitis C will be treated for up to eight years with ribavirin, an orally administered antiviral agent. Patients will be chosen who have moderate to severe chronic hepatitis C who previously failed to have a sustained virological response to the combination of alpha interferon and ribavirin or who were intolerant to interferon therapy or who have significant contraindications to the use of interferon.
After medical evaluation and liver biopsy, patients will begin receiving ribavirin in a dose of 1000 mg (body weight less than 75 K) or 1200 mg daily (two or three capsules of 200 mg twice daily by mouth). Patients will be followed on therapy with visits to the outpatient clinic for medical interview, physical examinations and blood tests at 2 to 8 week intervals. After six months, the dose of ribavirin will be stopped or adjusted based upon changes in alanine aminotransferase (ALT) levels comparing the average of the three values from month 2, 4, and 6 to the baseline levels. A decrease by 50% or more will be considered a partial biomedical response and a decrease to within the normal range will be considered a complete biochemical response. In patients who do not respond by six months, therapy will be stopped, whereas, in patients who respond, therapy will be continued decreasing the dose in increments of 200 mg per day every 6 months as long as a biochemical response is maintained. The minimal dose will be 400 mg per day. In patients with a response, therapy will be continued for up to 8 years with repeat liver biopsies and evaluations at 2, 4 and 8 years.
The primary criterion for success of therapy will be the degree of histologic improvement on liver biopsy at 2, 4 and 8 years; supportive, secondary criteria will be improvements in ALT levels and in symptoms done at the same time points. This open-label pilot study will allow for therapy of patients with resistant forms of chronic hepatitis C and will address whether long-term therapy with this agent is safe, as well as whether prolonged monotherapy with ribavirin leads to sustained improvements in serum ALT levels, whether these can be maintained using lower doses of ribavirin, and whether the improvements reflect amelioration of the underlying liver disease as judged histologically.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age above 18 years, male or female.
- Elevated alanine (ALT) or asparate (AST) aminotransferase activities averaging at least twice the upper limit of normal on three determinations taken at least one month apart during the previous 6 months. The mean of these three determinations will be defined as "baseline" ALT and AST levels.
- Presence of anti-HCV and HCV RNA in serum tested at least once during the previous six months.
- Evidence of chronic hepatitis on liver biopsy done within the previous 12 months with a histology activity index of at least 6 (out of a maximum of 22).
- Contraindications to the use of alpha interferon, either in the form of specific contraindications to its use (depression, psychiatric illness, neurological impairment, severe thrombocytopenia, autoimmune disease), or the history of severe side effects or intolerance during a previous course of alpha interferon, or lack of a sustained virological (sustained lost of HCV RNA from serum for more than six months after stopping treatment) response to an adequate course (6 months) of the combination of alpha interferon and ribavirin or (after September 1, 2003) the combination of peginterferon and ribavirin.
Key exclusion criteria (7 listed)
- Pregancy or, in women of childbearing potential, inability to practice adequate contraception. Men with spouses or sexual partners of childbearing potential also be excluded if they are unable to practice adequate contraception.
- Significant systemic illnesses other than liver disease, including a history of congestive heart failure, cerebral vascular disease, renal failure (creatinine clearance less than 50 ml/min), and angina pectoris.
- Patients with an abnormal stress test or carotid untrasound will not be enrolled into this study.
- Pre-existing anemia (hematocrit less than 32%) or known history of hemolytic anemia.
- Interferon or immunosuppressive therapy within the last 6 months.
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 |
|---|---|---|
| Ribavirin | Drug | – |
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 9755252Lau DT, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH. 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology. 1998 Oct;28(4):1121-7. doi: 10.1002/hep.510280430.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Ribavirin in people with Chronic Hepatitis C, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 7 inclusion and 7 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 2 Jul 2017. 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 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001854, which also lists 1 linked publication.
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 2 Jul 2017.