Chronic Hepatitis CPhase 2NCT00735969
High-Dose Ribavirin and Peginterferon to Treat Chronic Hepatitis C Genotype 1
A Phase 2 study testing Peginterferon and 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
This study will evaluate the effectiveness of an experimental treatment regimen for hepatitis C (HCV). Standard treatment consists of combination therapy with ribavirin, taken by mouth twice a day, and Peginterferon, injected under the skin once a week. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Peginterferon and Ribavirin
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Jun 2013
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or above, male or female
- Documented relapse or non-response to a prior adequate course of peginterferon and ribavirin
- Genotype 1 HCV as determined by probe specific hybridization (Inno-Lipa assay).
- Written informed consent.
Who cannot join
- Age greater than 65 years
- If cirrhosis is present, decompensated liver disease, as marked by serum bilirubin greater than 4 mg percent, albumin less than 3.0 gm percent, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy.
- Serum Alanine transaminase (ALT) or Aspartate transaminase (AST) levels greater than 1000 U/L (greater than 25 times the ULN). Such patients will not be enrolled but may be followed until three determinations are below this level.
- Pregnancy or, in women of child bearing potential or in spouses of pregnant women, inability to practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicide, or birth control pills, or an intrauterine device.
- Breastfeeding.
- Significant systemic or major illnesses including congestive heart failure, organ transplantation, serious psychiatric disease or depression, human immunodeficiency virus (HIV) infection, and angina pectoris.
Show all 20Show fewer
- Previous intolerance of weight based ribavirin dose (1,000-1,200 mg daily) including need for dose reduction, use of erythropoietin or serious adverse event attributable to ribavirin use.
- Renal insufficiency (creatinine clearance less than 60 ml/min) or renal failure
- Pre existing anemia (hematocrit less than 34 percent) or known history of hemolytic anemia.
- Uncontrolled hypertension or diabetes mellitus
- Other antiviral therapy within the last 6 months.
- Immunosuppressive therapy with either corticosteroids (more than 5 mg of prednisone daily) or major immunosuppressive agents (such as azathioprine or 6-mercaptopurine).
- Evidence of another form of liver disease in addition to viral hepatitis (for example autoimmune liver disease, Wilson disease, alcoholic liver disease, hemochromatosis, alpha 1 antitrypsin deficiency).
- Evidence of coronary artery disease or cerebral vascular disease, including abnormalities on exercise stress testing in patients with defined risk factors who will be screened for evidence of underlying coronary artery disease.
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous year.
- Evidence of hepatocellular carcinoma; either alpha-fetoprotein (AFP) levels greater than 200 ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study) demonstrating a mass suggestive of liver cancer.
- Clinical gout.
- Active, serious autoimmune disease, such as lupus erythematosis, ulcerative colitis, Crohn s disease or rheumatoid arthritis that in the opinion of the investigators might be exacerbated by therapy with peginterferon.
- Uncontrolled thyroid disease
- Evidence if severe retinopathy or clinically relevant ophthalmological disorder (only patients with pre-existing hypertension or diabetes will undergo an ophthalmological assessment).
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
Official title: High Dose Ribavirin in Combination With Peginterferon for Patients With Chronic Hepatitis C Genotype 1 Infection Who Have Failed to Respond or Relapsed After Standard Therapy
This study will evaluate the effectiveness of an experimental treatment regimen for hepatitis C (HCV). Standard treatment consists of combination therapy with ribavirin, taken by mouth twice a day, and Peginterferon, injected under the skin once a week. Hepatitis C genotypes 2 and 3 have a high success rate with this regimen, while genotype 1 is more difficult to treat. This study will determine if patients with genotype 1 respond better to treatment that uses a higher dose of ribavirin than the standard approved dose of 1,000 to 1,200 mg daily.
Patients 18 years of age and older with chronic hepatitis C genotype 1 who have not been successfully treated with a standard course of Peginterferon and ribavirin may be eligible for this study. Participants eligible will receive Peginterferon plus twice the standard dose of ribavirin (2,000 to 2,400 mg daily) for 48 weeks. In addition to treatment, all patients receive undergo the following:
Read more
Before Treatment:
- Medical history and physical examination, symptom questionnaires, blood tests, urine collection, chest x-ray, electrocardiogram, liver ultrasound, Fibroscan (ultrasound to measure stiffness of the liver) and pregnancy test for women who are able to have children.
- Patients with other medical conditions or special risk factors may have further evaluations before starting treatment. These may include, for example, eye evaluation for patients with diabetes, exercise stress test for people over age 40 or who have risk factors for heart disease and psychiatric evaluation for people who have depression or anxiety disorder.
During Treatment
- Periodic blood tests to monitor blood counts and viral levels.
- Outpatient clinic visits every 4 weeks for the duration of the study for laboratory tests and review of symptoms and treatment side effects. Physical examinations and urine tests are done every 12 weeks.
Following Completion of Treatment
About 1 1/2 years after starting treatment, subjects are re-evaluated as they were at the start of treatment.
...
Read the detailed description
Up to 60 patients with chronic hepatitis C genotype 1 infection who were previously treated with standard doses of peginterferon and ribavirin (1000 to 1200 mg daily) but who did not have a virological response (non-responders: n=35) or who relapsed after therapy (relapsers: n = 25) will be re-treated using peginterferon and higher doses of ribavirin (2000 to 2400 mg daily). After medical evaluation, documentation of eligibility and written informed consent, patients will be started on therapy with standard doses of peginterferon alfa-2a (180 micro g per week) and twice the standard dose of ribavirin (2000 mg daily for patients less than 75 kg; 2400 mg daily for patients greater than or equal to 75 kg). Viral kinetics will be evaluated on the basis of changes in HCV RNA levels during the first 24 weeks of therapy with blood sampling done on days 0, 1, and 2 and weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24. Patients who fail to decrease levels of HCV RNA by more than 2 log(10) IU/ml by week 12 will be considered non-responders and therapy will stop. Similarly, patients who do not become HCV RNA negative (less than 10 IU) by week 24 will also be considered non-responders and therapy will be discontinued. Patients who do become HCV RNA negative during the first 24 weeks of therapy will continue for 48 weeks and be followed for at least 24 weeks thereafter. The primary end-point of this study will be a sustained virological response (SVR), which is defined by the absence of detectable HCV RNA in serum on treatment and for at least 24 weeks after stopping therapy. The SVR rate for re-treatment using conventional doses of peginterferon and ribavirin is expected to be less than 5 percent. The estimated rate of SVR using peginterferon with high doses of ribavirin is 50 percent for patients with a previous relapse and 25 percent for those with a previous non-response. A sample size of 35 patients would be needed to achieve statistical significance based upon these estimates of response rates for non-responders and 25 patients for relapsers. If none of the first ten non-responder patients treated in this protocol achieve an SVR, no more non-responder patients will be enrolled and this part of the study will be terminated early. Patients also will be monitored closely for side effects of therapy, the major one for ribavirin being anemia. Patients who develop anemia will be treated with darbepoietin to maintain a hemoglobin level above 10 gm percent. This pilot study is expected to demonstrate whether use of high doses of ribavirin is an option for patients who fail to have an adequate response to conventional doses of peginterferon and ribavirin for chronic hepatitis C.
- Conditions
- Chronic Hepatitis C
- Being tested
- Peginterferon, Ribavirin
- Keywords
- Non-Responder, Relapser, High Dose Ribavirin, Peginterferon, Chronic Hepatitis C
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PeginterferonDrug
RibavirinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Virological Response, (HCV RNA Neg.) in Serum 24 Weeks Off Therapy.
Measured: 24 weeks after treatment stop
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionJun 2013
- Study completionJun 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.
- Publications (3)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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Marc Ghany, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Marc G Ghany, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00735969
- Sponsor's protocol ID
- 080149
- Other IDs
- 08-DK-0149
- Status last verified
- Oct 2014
- First submitted
- 14 Aug 2008
- Last updated
- 20 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000 Feb 15;132(4):296-305. doi: 10.7326/0003-4819-132-4-200002150-00008.
PubMed 10681285Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.
PubMed 16702586Nainan OV, Alter MJ, Kruszon-Moran D, Gao FX, Xia G, McQuillan G, Margolis HS. Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. Gastroenterology. 2006 Aug;131(2):478-84. doi: 10.1053/j.gastro.2006.06.007.
PubMed 16890602
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose Ribavirin in Combination With Peginterferon for Patients With Chronic Hepatitis C Genotype 1 Infection Who Have Failed to Respond or Relapsed After Standard Therapy
- ClinicalTrials.gov ID
- NCT00735969
- Acronym / sponsor ID
- 080149
- Conditions
- Chronic Hepatitis C
- Keywords
- Non-Responder, Relapser, High Dose Ribavirin, Peginterferon, Chronic Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Aug 2008
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 15 Aug 2008 (estimated)
- Results
- Posted 16 Sep 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 evaluate the effectiveness of an experimental treatment regimen for hepatitis C (HCV). Standard treatment consists of combination therapy with ribavirin, taken by mouth twice a day, and Peginterferon, injected under the skin once a week. Hepatitis C genotypes 2 and 3 have a high success rate with this regimen, while genotype 1 is more difficult to treat. This study will determine if patients with genotype 1 respond better to treatment that uses a higher dose of ribavirin than the standard approved dose of 1,000 to 1,200 mg daily.
Patients 18 years of age and older with chronic hepatitis C genotype 1 who have not been successfully treated with a standard course of Peginterferon and ribavirin may be eligible for this study. Participants eligible will receive Peginterferon plus twice the standard dose of ribavirin (2,000 to 2,400 mg daily) for 48 weeks. In addition to treatment, all patients receive undergo the following:
Before Treatment:
- Medical history and physical examination, symptom questionnaires, blood tests, urine collection, chest x-ray, electrocardiogram, liver ultrasound, Fibroscan (ultrasound to measure stiffness of the liver) and pregnancy test for women who are able to have children.
- Patients with other medical conditions or special risk factors may have further evaluations before starting treatment. These may include, for example, eye evaluation for patients with diabetes, exercise stress test for people over age 40 or who have risk factors for heart disease and psychiatric evaluation for people who have depression or anxiety disorder.
During Treatment
- Periodic blood tests to monitor blood counts and viral levels.
- Outpatient clinic visits every 4 weeks for the duration of the study for laboratory tests and review of symptoms and treatment side effects. Physical examinations and urine tests are done every 12 weeks.
Following Completion of Treatment
About 1 1/2 years after starting treatment, subjects are re-evaluated as they were at the start of treatment.
...
Detailed description
Up to 60 patients with chronic hepatitis C genotype 1 infection who were previously treated with standard doses of peginterferon and ribavirin (1000 to 1200 mg daily) but who did not have a virological response (non-responders: n=35) or who relapsed after therapy (relapsers: n = 25) will be re-treated using peginterferon and higher doses of ribavirin (2000 to 2400 mg daily). After medical evaluation, documentation of eligibility and written informed consent, patients will be started on therapy with standard doses of peginterferon alfa-2a (180 micro g per week) and twice the standard dose of ribavirin (2000 mg daily for patients less than 75 kg; 2400 mg daily for patients greater than or equal to 75 kg). Viral kinetics will be evaluated on the basis of changes in HCV RNA levels during the first 24 weeks of therapy with blood sampling done on days 0, 1, and 2 and weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24. Patients who fail to decrease levels of HCV RNA by more than 2 log(10) IU/ml by week 12 will be considered non-responders and therapy will stop. Similarly, patients who do not become HCV RNA negative (less than 10 IU) by week 24 will also be considered non-responders and therapy will be discontinued. Patients who do become HCV RNA negative during the first 24 weeks of therapy will continue for 48 weeks and be followed for at least 24 weeks thereafter. The primary end-point of this study will be a sustained virological response (SVR), which is defined by the absence of detectable HCV RNA in serum on treatment and for at least 24 weeks after stopping therapy. The SVR rate for re-treatment using conventional doses of peginterferon and ribavirin is expected to be less than 5 percent. The estimated rate of SVR using peginterferon with high doses of ribavirin is 50 percent for patients with a previous relapse and 25 percent for those with a previous non-response. A sample size of 35 patients would be needed to achieve statistical significance based upon these estimates of response rates for non-responders and 25 patients for relapsers. If none of the first ten non-responder patients treated in this protocol achieve an SVR, no more non-responder patients will be enrolled and this part of the study will be terminated early. Patients also will be monitored closely for side effects of therapy, the major one for ribavirin being anemia. Patients who develop anemia will be treated with darbepoietin to maintain a hemoglobin level above 10 gm percent. This pilot study is expected to demonstrate whether use of high doses of ribavirin is an option for patients who fail to have an adequate response to conventional doses of peginterferon and ribavirin for chronic hepatitis C.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 years or above, male or female
- Documented relapse or non-response to a prior adequate course of peginterferon and ribavirin
- Genotype 1 HCV as determined by probe specific hybridization (Inno-Lipa assay).
- Written informed consent.
Key exclusion criteria (20 listed)
- Age greater than 65 years
- If cirrhosis is present, decompensated liver disease, as marked by serum bilirubin greater than 4 mg percent, albumin less than 3.0 gm percent, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy.
- Serum Alanine transaminase (ALT) or Aspartate transaminase (AST) levels greater than 1000 U/L (greater than 25 times the ULN). Such patients will not be enrolled but may be followed until three determinations are below this level.
- Pregnancy or, in women of child bearing potential or in spouses of pregnant women, inability to practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicide, or birth control pills, or an intrauterine device.
- Breastfeeding.
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 |
|---|---|---|
| Peginterferon | Drug | – |
| Ribavirin | Drug | – |
Primary outcome
Sustained Virological Response, (HCV RNA Neg.) in Serum 24 Weeks Off Therapy.
Time frame: 24 weeks after treatment stop
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10681285Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000 Feb 15;132(4):296-305. doi: 10.7326/0003-4819-132-4-200002150-00008.
- Background: PubMed 16702586Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.
- Background: PubMed 16890602Nainan OV, Alter MJ, Kruszon-Moran D, Gao FX, Xia G, McQuillan G, Margolis HS. Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. Gastroenterology. 2006 Aug;131(2):478-84. doi: 10.1053/j.gastro.2006.06.007.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Marc G Ghany, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Peginterferon and 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 4 inclusion and 20 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 20 Oct 2014. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Sep 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?
Sustained Virological Response, (HCV RNA Neg.) in Serum 24 Weeks Off Therapy. (time frame: 24 weeks after treatment stop). 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 NCT00735969, which also lists 3 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 20 Oct 2014.