Hepatitis C, ChronicPhase 4NCT00127777
Peginterferon Alfa-2a, Ribavirin, Amantadine/Placebo in Hepatitis C Virus (HCV)-Genotype-1-Infection (PRAMA)
A Phase 4 study testing Amantadine sulphate (in addition to standard treatment) in people with Hepatitis C, Chronic, run by University Hospital, Saarland.
Trial summary
This was a randomized, multi-center, partially placebo-controlled Phase IV study to compare the efficacy and tolerability of a 48-week combined therapy with pegylated interferon alpha-2a, ribavirin and amantadine sulphate versus placebo in untreated patients with chronic hepatitis C virus-genotype-1-infection. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- Amantadine sulphate (in addition to standard treatment)
- How many people
- 700 participants
- Where
- No sites listed yet
- Study dates
- Jul 2002to Dec 2006
- 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
- Female and male subjects over 18 years of age and below 70 years of age
- Serological indication of chronic hepatitis C infection with positive anti-HCV test and serum HCV-RNA quantification >600 IE/ml by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor test, v.2.0.
- Untreated patients with HCV-induced chronic infection.
- Indication of a genotype HCV-1 on the basis of the reverse hybridizing assay Inno LiPA from Bayer Versant (Innogenetics).
- Increased GPT serum level on at least one determination date within the 56-day screening phase prior to start of administration of study medication.
- Histological identification of inflammatory activity in the liver, with or without an indication of compensated cirrhosis, during the 24 months prior to start of the study.
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- Compensated liver disease (Child-Pugh Grade A).
- Negative urine or serum pregnancy test in fertile female subjects within 24 hours before taking the first dose of study medication.
- During the administration of study medication and for 24 weeks after the treatment has stopped, patients must apply two approved contraception methods, one of which must have a barrier effect on the male, e.g. condom.
- If one or more of the above inclusion criteria are not fulfilled, the patient is excluded from the study!
Who cannot join
- Any known sensitive reaction to interferon, ribavirin or amantadine sulphate.
- Pregnant or breast-feeding women and fertile women who do not practice contraception.
- Male partners of pregnant women.
- Previous treatment with interferon and/or ribavirin.
- Treatment with systemic anti-neoplastic or immunomodulatory medication (supraphysiologic doses of steroids or radiation included) within the last 6 months prior to the study and throughout the whole study.
- Immunosuppressed/immunocompromised patients.
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- Participation in a clinical study within the last three months.
- Infection with HCV genotype-2, -3, -4, -5 or -6.
- Positive indication of HBsAg, HIV antibodies in the screening phase.
- Non-hepatitis C virus-induced chronic hepatitis (e.g. hematochromatosis, autoimmune hepatitis, metabolic or alcoholic liver disease).
- Decompensated liver cirrhosis or liver disease; Child-Pugh Grade B or C; or threshold compensated liver disease.
- Signs of a hepatocellular carcinoma within 2 months before the randomization, coupled with existing or developing cirrhosis.
- History of oesophagus varices haemorrhage.
- Hemoglobin <12 g/dl in female subjects and <13 g/dl in male subjects in the screening phase.
- Subjects with a higher risk of anemia (e.g. thalassemia, spherocytosis, history of gastrointestinal bleeding) or subjects for whom anemia could be a highly potential medical risk.
- Neutropenia <1500 /µl or thrombocytopenia <90,000 /µl diagnosed in the screening phase.
- Serum creatinine >1.5 mg/dl in the screening phase.
- History of severe psychiatric diseases, especially severe depression, whereby severe psychiatric disease is defined as any anti-depressive or anti-psychotic therapy of at least 3 months in the history, or any indication of suicidal inclination or hospitalization caused by a psychiatric disease.
- Epilepsy.
- Autoimmune disease (e.g. inflammatory intestinal diseases, idiopathic thrombocytopenic purpura, lupus erythematosus sclerodermia, severe psoriasis, rheumatoid arthritis, etc.).
- History of thyroid disease, poorly controlled by prescribed medications
- Chronic pulmonary disease with functional restriction.
- History of severe cardiac disease, e.g. cardiac insufficiency New York Heart Association (NYHA) class III or IV; myocardial infarction within the last 6 months; ventricular tachyarrhythmia requiring treatment; unstable angina pectoris; cerebrovascular circulation disorders; or other significant cardiovascular diseases.
- Patients with pacemakers.
- Cardiomyopathy and myocarditis
- Atrioventricular (AV)-block Grade II and III.
- Previously known bradycardia rating under 55 strokes/minute
- Known, lengthy QT-interval (QTc as per Bazett > 420 ms) or recognizable U waves or hereditary QT-syndrome in the family history.
- History of a severe ventricular arrythmia including Torsade de pointes.
- Simultaneous therapy with budipine or other QT-extending medication such as:
- Certain antiarrhythmias of class IA (e.g. quinidine, disopyramide, procainamide) and class III (such as amiodarone, sotalol);
- Certain antipsychotics (e.g. thioridazine, chlorpromazine, haloperidol, pimozide);
- Certain tri- and tetracyclic anti-depressive medications (e.g. amitriptyline);
- Certain antihistaminic medications (e.g. astemizol, terfenadin);
- Certain macrolide antibiotics (e.g. erythromycin, clarithromycin);
- Certain gyrase inhibitors (e.g. sparfloxacin);
- Azole-antimycotics and other medications such as halofantrine, cotrimoxazol, pentamidine, cisapride or bepridil;
- Simultaneous treatment with Memantine.
- Morbus Parkinson.
- History of major organ transplantations, with the exception of cornea transplantation.
- Cancer or any other disease, which, in the opinion of the investigator, is an exclusion criterion for the study.
- Evidence of severe retinopathy (e.g. cytomegalovirus [CMV] retinitis or macular degeneration).
- Patients with narrow-angle glaucoma.
- Active drug abuse (excessive alcohol consumption included) within the last year prior to study (with the exception of a prescribed substitute).
- Patients with state of agitation or confusion
- Patients with a history of acute brain syndrome or exogenous psychosis
- Patients are already enrolled in the study.
- Prostate hypertrophy
- Simultaneous administering of diuretics of combination type triamterene/hydrochlorothiazide.
- Unwillingness or incapability to give written consent after receiving medical information; doubts about the proper protection of patient data; and general reluctance to take part in the study and to adhere to the study terms.
- If one or more of these exclusion criteria is fulfilled, the patient shall be excluded from the study!
About this study
Official title: Randomized, Multi-Center, Partially Placebo-Controlled Phase IV-Study to Compare Efficacy and Tolerability of 48-Week Combined Therapy With Peginterferon Alfa-2a, Ribavirin and Amantadine Sulphate Versus Placebo in Untreated Patients With Chronic Hepatitis C Virus-Genotype-1-Infection
This was a randomized, multi-center, partially placebo-controlled Phase IV study to compare the efficacy and tolerability of a 48-week combined therapy with pegylated interferon alpha-2a, ribavirin and amantadine sulphate versus placebo in untreated patients with chronic hepatitis C virus-genotype-1-infection. The hypothesis was that there will be an increase in sustained response rate for triple therapy compared to current standard treatment.
Read the detailed description
Primary Objective:
- Proof that a triple-therapy (peginterferon alfa-2a, ribavirin and amantadine sulphate) dispensed over a period of 50 weeks, improves the permanent virological efficacy by more than 10% as compared to a combination therapy with peginterferon alpha-2a and ribavirin, defined as negative HCV-RNA result obtained by a molecular verification method (e.g. Roche AmplicorTM HCV, v.2.0, sensitivity <50 IE/ml) 24 weeks after the end of the therapy.
Secondary Objectives:
- Verification of the initial virological efficacy up to week 12, defined as negative HCV-RNA test results by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor v.2.0 (sensitivity <600 IE/ml).
- Biochemical efficacy, defined by the serum GPT values 24 weeks after the end of the therapy.
- Virological efficacy, measured on the basis of the HCV-RNA values at the end of the therapy.
- Biochemical efficacy defined by the serum GPT values at the end of the therapy.
- Conditions
- Hepatitis C, Chronic
- Being tested
- Amantadine sulphate (in addition to standard treatment)
- Keywords
- HCV genotype 1, peginterferon alfa-2a, ribavirin, amantadine, treatment-naive
- 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.
Amantadine sulphate (in addition to standard treatment)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Proof that peginterferon alfa-2a, ribavirin and amantadine sulphate over a period of 50 weeks improves the permanent virological efficacy by more than 10% compared to peginterferon alfa-2a and ribavirin
Secondary outcomes (4)
Verification of the initial virological efficacy up to week 12, defined as negative HCV-RNA test results by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor v.2.0 (sensitivity <600 IE/ml)
Biochemical efficacy, defined by the serum GPT values 24 weeks after the end of the therapy
Virological efficacy, measured on the basis of the HCV-RNA values at the end of the therapy
Biochemical efficacy defined by the serum GPT values at the end of the therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2005 (estimated)
- Study startJul 2002
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis C, ChronicStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 700 participants
Sponsor and investigators
- Lead sponsor
- University Hospital, Saarland
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Investigators
- Stefan Zeuzem, MD, Principal investigator, Saarland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00127777
- Sponsor's protocol ID
- ML17002
- Status last verified
- Aug 2005
- First submitted
- 4 Aug 2005
- Last updated
- 25 Aug 2005
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Multi-Center, Partially Placebo-Controlled Phase IV-Study to Compare Efficacy and Tolerability of 48-Week Combined Therapy With Peginterferon Alfa-2a, Ribavirin and Amantadine Sulphate Versus Placebo in Untreated Patients With Chronic Hepatitis C Virus-Genotype-1-Infection
- ClinicalTrials.gov ID
- NCT00127777
- Acronym / sponsor ID
- ML17002
- Conditions
- Hepatitis C, Chronic
- Keywords
- HCV genotype 1, peginterferon alfa-2a, ribavirin, amantadine, treatment-naive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 700 participants
- Lead sponsor
- University Hospital, SaarlandUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Jul 2002
- Study completion
- Dec 2006
- First posted
- 8 Aug 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.
This was a randomized, multi-center, partially placebo-controlled Phase IV study to compare the efficacy and tolerability of a 48-week combined therapy with pegylated interferon alpha-2a, ribavirin and amantadine sulphate versus placebo in untreated patients with chronic hepatitis C virus-genotype-1-infection. The hypothesis was that there will be an increase in sustained response rate for triple therapy compared to current standard treatment.
Detailed description
Primary Objective:
- Proof that a triple-therapy (peginterferon alfa-2a, ribavirin and amantadine sulphate) dispensed over a period of 50 weeks, improves the permanent virological efficacy by more than 10% as compared to a combination therapy with peginterferon alpha-2a and ribavirin, defined as negative HCV-RNA result obtained by a molecular verification method (e.g. Roche AmplicorTM HCV, v.2.0, sensitivity <50 IE/ml) 24 weeks after the end of the therapy.
Secondary Objectives:
- Verification of the initial virological efficacy up to week 12, defined as negative HCV-RNA test results by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor v.2.0 (sensitivity <600 IE/ml).
- Biochemical efficacy, defined by the serum GPT values 24 weeks after the end of the therapy.
- Virological efficacy, measured on the basis of the HCV-RNA values at the end of the therapy.
- Biochemical efficacy defined by the serum GPT values at the end of the therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female and male subjects over 18 years of age and below 70 years of age
- Serological indication of chronic hepatitis C infection with positive anti-HCV test and serum HCV-RNA quantification >600 IE/ml by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor test, v.2.0.
- Untreated patients with HCV-induced chronic infection.
- Indication of a genotype HCV-1 on the basis of the reverse hybridizing assay Inno LiPA from Bayer Versant (Innogenetics).
- Increased GPT serum level on at least one determination date within the 56-day screening phase prior to start of administration of study medication.
Key exclusion criteria (51 listed)
- Any known sensitive reaction to interferon, ribavirin or amantadine sulphate.
- Pregnant or breast-feeding women and fertile women who do not practice contraception.
- Male partners of pregnant women.
- Previous treatment with interferon and/or ribavirin.
- Treatment with systemic anti-neoplastic or immunomodulatory medication (supraphysiologic doses of steroids or radiation included) within the last 6 months prior to the study and throughout the whole study.
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 |
|---|---|---|
| Amantadine sulphate (in addition to standard treatment) | Drug | – |
Primary outcome
Proof that peginterferon alfa-2a, ribavirin and amantadine sulphate over a period of 50 weeks improves the permanent virological efficacy by more than 10% compared to peginterferon alfa-2a and ribavirin
4 secondary outcomes
Verification of the initial virological efficacy up to week 12, defined as negative HCV-RNA test results by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor v.2.0 (sensitivity <600 IE/ml)
Biochemical efficacy, defined by the serum GPT values 24 weeks after the end of the therapy
Virological efficacy, measured on the basis of the HCV-RNA values at the end of the therapy
Biochemical efficacy defined by the serum GPT values at the end of the therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2005.
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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.
Stefan Zeuzem, MD principal investigator
Saarland University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amantadine sulphate (in addition to standard treatment) in people with Hepatitis C, Chronic, run by University Hospital, Saarland.
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 10 inclusion and 51 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: status not confirmed, as of the sponsor's last update on 25 Aug 2005. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
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?
Proof that peginterferon alfa-2a, ribavirin and amantadine sulphate over a period of 50 weeks improves the permanent virological efficacy by more than 10% compared to peginterferon alfa-2a and ribavirin. 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 25 Aug 2005.