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

NCT00662220 | Terminated Phase 3 DMC

• 2 other identifiers: HCV07-012007-005344-25
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 27

Brief 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. 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).

Conditions

Chronic Hepatitis C

Keywords

chronic; hepatitis C; ribavirin; SVR; genotype one; genotype four

Outcome Measures

Primary Outcomes (1)

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

  72 weeks

Secondary Outcomes (8)

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

  4 weeks

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

  12 weeks

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

  12 weeks

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

  48 weeks

• Relapse rate after ETR

  48 weeks - end of follow up

Study Arms (2)

Standard dose

ACTIVE COMPARATOR

Standard-dose ribavirin (12-15 mg/kg/day) in combination with peginterferon 180µg QW

Drug: ribavirin

High dose

EXPERIMENTAL

High-dose ribavirin (25-29 mg/kg/day) in combination with peginterferon 180µg QW

Drug: ribavirin

Interventions

ribavirin DRUG

25-29 mg/kg/day

Also known as: Copegus, Pegasys, NeoRecormon

High dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Foundation for Liver Research: lead
• Hoffmann-La Roche: collaborator

Study Sites (27)

Rijnstate

Arnhem, Gelderland, 6815AD, Netherlands

Location

St. Radboud University Medical Center

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Canisius-Wilhelmina Ziekenhuis

Nijmegen, Gelderland, 6532 SZ, Netherlands

Location

Atrium Medisch Centrum

Heerlen, Limburg, 6401CX, Netherlands

Location

Amphia hospital

Breda, North Brabant, 4818CK, Netherlands

Location

Catharina hospital

Eindhoven, North Brabant, 5602ZA, Netherlands

Location

Twee Steden hospital

Tilburg, North Brabant, 5000LA, Netherlands

Location

St. Elisabeth hospital

Tilburg, North Brabant, 5000LC, Netherlands

Location

Medisch Centrum Alkmaar

Alkmaar, North Holland, 1815JD, Netherlands

Location

Slotervaart hospital

Amsterdam, North Holland, 1006BK, Netherlands

Location

VU Medisch Centrum

Amsterdam, North Holland, 1007 MB, Netherlands

Location

Onze Lieve Vrouwen Gasthuis

Amsterdam, North Holland, 1090HM, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, North Holland, 2130 AT, Netherlands

Location

Deventer hospital

Deventer, Overijssel, 7415CM, Netherlands

Location

Groningen University Medical Center

Groningen, Provincie Groningen, 9713GZ, Netherlands

Location

St. Lucas hospital

Winschoten, Provincie Groningen, 9670RA, Netherlands

Location

IJsselland hospital

Capelle aan den IJssel, South Holland, 2906ZC, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, South Holland, 2600GA, Netherlands

Location

Albert Schweitzer hospital

Dordrecht, South Holland, 3300AK, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, South Holland, 2300 RC, Netherlands

Location

St Franciscus hospital

Rotterdam, South Holland, 3004BA, Netherlands

Location

Erasmus MC University Medical Center

Rotterdam, South Holland, 3015CE, Netherlands

Location

Maasstad hospital

Rotterdam, South Holland, 3078HT, Netherlands

Location

HAGA Ziekenhuis

The Hague, South Holland, 2545CH, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Utrecht, 3584CX, Netherlands

Location

Walcheren hospital

Flushing, Zeeland, 3200, Netherlands

Location

ZorgSaam Hospital

Terneuzen, Zeeland, 4535PA, Netherlands

Location

Related Links

• Study website

MeSH Terms

Conditions

Hepatitis C, Chronic; Bronchiolitis Obliterans Syndrome; Hepatitis C

Interventions

Ribavirin; peginterferon alfa-2a; epoetin beta

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• R J de Knegt, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• J PH Drenth, MD PhD

  St Radboud Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2008
• First Posted: April 21, 2008
• Study Start: April 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: November 1, 2013
• Last Updated: July 14, 2014

Record last verified: 2014-07

Locations

NL (27)