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Chronic Hepatitis CPhase 3VIRIDNCT00662220

High-dose Ribavirin in Treatment of Chronic Hepatitis C Genotype 1 or 4

A Phase 3 study testing ribavirin in people with Chronic Hepatitis C, run by Foundation for Liver Research at 27 sites in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Optimal ribavirin dosages are essential in achieving SVR (sustained virological response). Several studies have shown higher SVR rates in patients receiving higher doses of ribavirin. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Chronic Hepatitis C
What is being tested?
ribavirin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
110 participants
Where
27 sitesNetherlands
Study dates
Apr 2008to Nov 2013
Phase
Phase 3
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

  • hepatitis C genotype 1 or 4
  • high viral load (>400000 IU/ml)
  • indication for antiviral treatment or patient's desire for antiviral treatment
  • hepatitis C treatment naive
  • liver biopsy within 3 years of screening visit or when biopsy is contraindicated e.g in patients with clotting diseases or when a patient refuses to undergo a new biopsy in case the liver biopsy is older than 3 years, substitution by fibroscan is allowed.
  • age 18-70 years

Who cannot join

  • serum bilirubin >35 μmol/l
  • albumin <36 g/l
  • prothrombin time >4 sec prolonged
  • platelets <90x109/l
  • decompensated cirrhosis (Child-Pugh Grade B or C)
  • hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma (hepatic imaging should be performed within 3 months prior to screening for cirrhotic patients and within 6 months prior to screening for non-cirrhotic patients)
Show all 27Show fewer
  • alcoholic liver disease (indicator: MCV>100)
  • obesity induced liver disease (indicators: steatosis proven by biopsy or ultrasound in association with a body mass index >30)
  • drug related liver disease (indicator: positive history of hepatic toxic drug intake with a causal relation)
  • auto-immune hepatitis (indicators: IgG >30g/l, anti smooth-muscle or antinuclear antibodies titer ³1:40)
  • hemochromatosis (indicator: ferritin >1000 μg/l)
  • Wilson's disease (indicator: ceruloplasmin (<0.2 g/l)
  • alpha-1 antitrypsin deficiency (indicator alpha-1 antitrypsin <0.8 g/L)
  • co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
  • any cardiovascular dysfunction (e.g. cardiac decompensation, myocardial infarction, present or history of arrythmia)
  • other medical illness that might interfere with this study: significant pulmonary or renal dysfunction, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g.: steroid therapy, organ transplants other than cornea and hair transplant)
  • contra-indications for peginterferon and/or ribavirin:
  • severe psychiatric disorder, such as major psychoses, suicidal ideation, suicidal attempt and/or manifest depression. Severe depression would include the following: (a) subjects who have been hospitalized for depression, (b) subjects who have received electroconvulsive therapy for depression, or (c) subjects whose depression has resulted in a prolonged absence of work and/or significant disruption of daily functions. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject's mental status supports that the subject is clinically stable and that there is ongoing evaluation of the patient's mental status during the study
  • visual symptoms related to retinal abnormalities
  • pregnancy, breast-feeding or inadequate contraception
  • thalassemia, spherocytosis
  • females who are pregnant or intending to become pregnant or male partners of females who are pregnant or intending to become pregnant
  • absolute neutrophil count (ANC) <1.40x109/l
  • hemoglobin (Hb) <7.5 mmol/l (female) or <8.1 mmol/l (male)
  • serum creatinine concentration >1.5 times the upper limit of normal at screening
  • substance abuse, such as I.V. drugs or alcohol (indicator: >28 drinks/week). If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 1 year
  • any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

Netherlands27 sites

  • Medisch Centrum Alkmaar

    Alkmaar, North Holland, 1815JD

  • Slotervaart hospital

    Amsterdam, North Holland, 1006BK

  • VU Medisch Centrum

    Amsterdam, North Holland, 1007 MB

  • Onze Lieve Vrouwen Gasthuis

    Amsterdam, North Holland, 1090HM

  • Rijnstate

    Arnhem, Gelderland, 6815AD

  • Amphia hospital

    Breda, North Brabant, 4818CK

  • IJsselland hospital

    Capelle aan den IJssel, South Holland, 2906ZC

  • Reinier de Graaf Gasthuis

    Delft, South Holland, 2600GA

  • Deventer hospital

    Deventer, Overijssel, 7415CM

  • Albert Schweitzer hospital

    Dordrecht, South Holland, 3300AK

  • Catharina hospital

    Eindhoven, North Brabant, 5602ZA

  • Walcheren hospital

    Flushing, Zeeland, 3200

  • Groningen University Medical Center

    Groningen, Provincie Groningen, 9713GZ

  • Atrium Medisch Centrum

    Heerlen, Limburg, 6401CX

  • Spaarne Ziekenhuis

    Hoofddorp, North Holland, 2130 AT

  • Leids Universitair Medisch Centrum

    Leiden, South Holland, 2300 RC

  • St. Radboud University Medical Center

    Nijmegen, Gelderland, 6525GA

  • Canisius-Wilhelmina Ziekenhuis

    Nijmegen, Gelderland, 6532 SZ

  • St Franciscus hospital

    Rotterdam, South Holland, 3004BA

  • Erasmus MC University Medical Center

    Rotterdam, South Holland, 3015CE

  • Maasstad hospital

    Rotterdam, South Holland, 3078HT

  • ZorgSaam Hospital

    Terneuzen, Zeeland, 4535PA

  • HAGA Ziekenhuis

    The Hague, South Holland, 2545CH

  • Twee Steden hospital

    Tilburg, North Brabant, 5000LA

  • St. Elisabeth hospital

    Tilburg, North Brabant, 5000LC

  • Universitair Medisch Centrum Utrecht

    Utrecht, Utrecht, 3584CX

  • St. Lucas hospital

    Winschoten, Provincie Groningen, 9670RA

Other trials in Netherlands

About this study

Official title: High-dose Versus Standard-dose Weight-based Ribavirin in Combination With Peginterferon Alfa-2a for Patients Infected With Hepatitis C Virus Genotype 1 or 4

Optimal ribavirin dosages are essential in achieving SVR (sustained virological response). Several studies have shown higher SVR rates in patients receiving higher doses of ribavirin. Therefore we propose a randomized controlled open label multicenter trial to investigate wether high (25-29mg/kg) dose ribavirin can improve outcome in patients in infected with hepatitis C virus genotype 1 or 4 compared to standard dose (12-15mg/kg).

Read the detailed description

Optimal ribavirin dosages are essential in achieving SVR. The initial evidence supporting higher doses of ribavirin for peginterferon alfa-2b comes from a secondary analysis of the pivotal multicenter trial of peginterferon alfa-2b and ribavirin. Patients receiving more than 10.6 mg/kg/day ribavirin experienced significantly higher SVR rates (48% vs. 38%). A large multicenter trial designed to test standard dose ribavirin (1000-1200 mg/day) versus low-dose ribavirin (800 mg/day) in combination with peginterferon alfa-2a, showed 52% SVR in the standard dose group versus 41% in the low-dose group for genotype 1 infected patients. In the pooled data from two pivotal studies with peginterferon alfa-2a and ribavirin, the probability of achieving an SVR for genotype 1 patients was influenced by the ribavirin dose per kg body weight. A 40-50% increase in the probability of SVR was found for a 12-16 mg/kg dose increase of ribavirin. For peginterferon alfa-2b it was also shown among genotype 1 patients, that weight-based ribavirin (800-1400 mg/day) leads to higher SVR rates compared to fixed dose ribavirin (800 mg/day) (34% vs. 29%). Moreover, ribavirin dosing up to 1400 mg/day was safe and the rate of treatment discontinuation was the same for both treatment groups. In a small pilot study, 10 genotype 1 patients with a high baseline load were treated with peginterferon alfa-2a and individualized high-dose ribavirin in order to achieve a ribavirin target concentration in serum of 15 μmol/l. The mean ribavirin dose of 2540 mg/day (range 1600-3600 mg/day) was high, but resulted in 90% SVR. All patients experienced severe anemia, which was treated with concomitant epoetin beta and blood transfusion.

As mentioned before, the main concern of high-dose ribavirin will be a dose-dependent hemolytic anemia and the addition of epoetin alfa has shown significant increase of haemoglobin during (peg)interferon/ribavirin therapy. Erythropoietin doses from 9,000 to 60,000 IU/week have been used in order keep the highest possible ribavirin doses. A recent trial showed a significant higher SVR rate in genotype 1 patients treated with peginterferon alfa-2b, increased dose ribavirin (15.2 mg/kg/day) and epoetin alfa than in patients treated with peginterferon alfa-2b and standard dose ribavirin (13.3 mg/kg/day) with or without epoetin alfa. Using the standard ribavirin dose, routine use of erythropoietin significantly decreased the frequency of anemia and the mean ribavirin dose reduction. Moreover, with the addition of erythropoietin, a significant higher mean dose could be given to patients in the increased ribavirin dose arm.

Being tested
ribavirin
Keywords
chronic, hepatitis C, ribavirin, SVR, genotype one, genotype four
Medical subject headings
Hepatitis C, Chronic, Bronchiolitis Obliterans Syndrome, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ribavirinDrug

    Also called Copegus, Pegasys, NeoRecormon

    25-29 mg/kg/day

  • ribavirinDrug

    Also called Copegus, Pegasys, NeoRecormon

    12-15 mg/kg/day

Study groups in NCT00662220
Study groupRoleWhat they receive
Standard doseActive comparatorStandard-dose ribavirin (12-15 mg/kg/day) in combination with peginterferon 180µg QW
Receives: Drug: ribavirin
High doseExperimentalHigh-dose ribavirin (25-29 mg/kg/day) in combination with peginterferon 180µg QW
Receives: Drug: ribavirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HCV-RNA negativity by qualitative assay 24 weeks after end of treatment (sustained virological response, SVR)

    Measured: 72 weeks

Secondary outcomes (8)

  1. HCV-RNA negativity at week 4 (rapid virological response, RVR)

    Measured: 4 weeks

  2. HCV-RNA negativity at week 12 (complete early virological response, cEVR)

    Measured: 12 weeks

  3. HCV-RNA ≥ 2log10 drop at week 12, but HCV-RNA still detectable (partial early virological response, pEVR)

    Measured: 12 weeks

  4. HCV- RNA negativity at week 48 (end of treatment response, ETR)

    Measured: 48 weeks

  5. Relapse rate after ETR

    Measured: 48 weeks - end of follow up

  6. Safety and tolerability of high-dose daily ribavirin (serious adverse events, grade 4 NCI toxicity, percentage of patients completing treatment on full or >80% of total intended dose and reasons for dose adjustments)

    Measured: week 0 till end of follow up

  7. Biochemical response (normalization of serum ALT at the end of therapy and at the end of follow-up)

    Measured: week 0 - end of follow up

  8. Health related quality of life and psychopathology before, during and after treatment by SF-36 and SCL-90 questionnaires

    Measured: week 0 - week 72

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionJun 2013
  4. Study completionNov 2013

Why it stopped: Due to the arrival of DAAs replacing standard of care for genotype 1 patients the VIRID study had to be terminated.

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00662220
Sponsor's protocol ID
HCV07-01
Other IDs
2007-005344-25
Acronym
VIRID
Status last verified
Jul 2014
First submitted
17 Apr 2008
Last updated
14 Jul 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ribavirin in people with Chronic Hepatitis C, run by Foundation for Liver Research at 27 sites in Netherlands.

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 6 inclusion and 27 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: stopped early, as of the sponsor's last update on 14 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 stopped early (reason given: Due to the arrival of DAAs replacing standard of care for genotype 1 patients the VIRID study had to be terminated.). 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?

HCV-RNA negativity by qualitative assay 24 weeks after end of treatment (sustained virological response, SVR) (time frame: 72 weeks). 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 NCT00662220.

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 14 Jul 2014.

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