NCT00532701

Brief Summary

Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% versus 79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. The investigators aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
880

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2007

Longer than P75 for phase_4

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 18, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 20, 2007

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2007

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
Last Updated

June 4, 2014

Status Verified

June 1, 2014

Enrollment Period

6.3 years

First QC Date

September 18, 2007

Last Update Submit

June 3, 2014

Conditions

Chronic Hepatitis C

Keywords

Chronic hepatitis CGenotypeInterferonRibavirinGenotype 2Peginterferon

Outcome Measures

Primary Outcomes (1)

  • Sustained virologic response (SVR)

    1.5 year

Secondary Outcomes (2)

  • Histologic response (HR)

    1.5 year

  • Biochemical response (BR)

    1.5

Study Arms (5)

Peg-IFN + WB RBV for 16 weeks

ACTIVE COMPARATOR

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-16 in patients with RVR

Drug: Peg-IFN + WB RBV for 16 weeks

Peg-IFN + LD RBV for 16 weeks

ACTIVE COMPARATOR

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-6, and then low dose ribavirin (800 mg/day) from weeks 6-16 in patients with RVR

Drug: Peg-IFN + LD RBV for 16 weeks

Peg-IFN + WB RBV for 24 weeks

ACTIVE COMPARATOR

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-24 in patients without RVR

Drug: Peg-IFN + WB RBV for 24 weeks

Peg-IFN + WB RBV for 48 weeks

ACTIVE COMPARATOR

Weight-based ribavirin (1000-1200 mg/day) from weeks 1-48 in patients without RVR

Drug: Peg-IFN + WB RBV for 48 weeks

Peg-IFN + LD RBV for 24 weeks

ACTIVE COMPARATOR

Low dose ribavirin (800 mg/day) from weeks 1-24 in patients with or without RVR

Drug: Peg-IFN + LD RBV for 24 weeks

Interventions

Peg-IFN + WB RBV for 16 weeksDRUG

1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (\< 75 kg, 1000 mg/day; \>= 75 kg, 1200 mg/day) from weeks 1-4 2. Rapid virologic response (RVR) at week 4 of therapy: achieved 3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (\< 75 kg, 1000 mg/day; \>= 75 kg, 1200 mg/day) from weeks 5-16

Also known as: Pegasys plus Copegus
Peg-IFN + WB RBV for 16 weeks
Peg-IFN + LD RBV for 16 weeksDRUG

1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (\< 75 kg, 1000 mg/day; \>= 75 kg, 1200 mg/day) from weeks 1-6 2. Rapid virologic response (RVR) at week 4 of therapy: achieved 3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 800 mg/day from weeks 6-16

Also known as: Pegasys plus Copegus
Peg-IFN + LD RBV for 16 weeks
Peg-IFN + WB RBV for 24 weeksDRUG

1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (\< 75 kg, 1000 mg/day; \>= 75 kg, 1200 mg/day) from weeks 1-4 2. Rapid virologic response (RVR) at week 4 of therapy: not achieved 3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day from weeks 5-24

Also known as: Pegasys plus Copegus
Peg-IFN + WB RBV for 24 weeks
Peg-IFN + WB RBV for 48 weeksDRUG

1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (\< 75 kg, 1000 mg/day; \>= 75 kg, 1200 mg/day) from weeks 1-4 2. Rapid virologic response (RVR) at week 4 of therapy: not achieved 3. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day from weeks 5-48

Also known as: Pegasys plus Copegus
Peg-IFN + WB RBV for 48 weeks
Peg-IFN + LD RBV for 24 weeksDRUG

1. Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 800 mg/day from weeks 1-24 2. Rapid virologic response (RVR) at week 4 of therapy: both achieved and not achieved

Also known as: Pegasys plus Copegus
Peg-IFN + LD RBV for 24 weeks

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Treatment naïve
  • Age older than 18 years old
  • Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive \> 6 months
  • Detectable serum quantitative HCV-RNA (Cobas Taqman HCV Monitor v2.0, Roche Diagnostics) with dynamic range 25 \~ 391000000 IU/ml
  • HCV genotype 2 (Inno-LiPA HCV II, Innogenetics, Ghent, Belgium)
  • Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment
  • A liver biopsy consistent with the diagnosis of chronic hepatitis C

You may not qualify if:

  • Anemia (hemoglobin \< 13 grams per deciliter for men and \< 12 grams per deciliter for women)
  • Neutropenia (neutrophil count \< 1,500 per cubic milliliter)
  • Thrombocytopenia (platelets \< 90,000 per cubic milliliter)
  • Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
  • Chronic alcohol abuse (daily consumption \> 20 grams per day)
  • Decompensated liver disease (Child-Pugh class B or C)
  • Serum creatinine level more than 1.5 times the upper limit of normal
  • Autoimmune liver disease
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to use contraception
  • Unwilling to sign informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

National Taiwan University Hospital, Yun-Lin Branch

Douliu, Taiwan

Location

Kaohsiung Medical University

Kaohsiung City, Taiwan

Location

Kaohsiung Municipal Hsiao-Kang Hospital

Kaohsiung City, Taiwan

Location

Paochien Hospital

Pingtung City, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Buddhist Xindian Tzu Chi General Hospital

Taipei, Taiwan

Location

Far Eastern Memorial Hospital

Taipei, Taiwan

Location

Ren-Ai Branch, Taipei Municipal Hospital

Taipei, Taiwan

Location

Related Publications (11)

  • Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5.

    PMID: 11583749BACKGROUND

  • Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047.

    PMID: 12324553BACKGROUND

  • Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55. doi: 10.7326/0003-4819-140-5-200403020-00010.

    PMID: 14996676BACKGROUND

  • Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, Sarrazin C, Harvey J, Brass C, Albrecht J. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004 Jun;40(6):993-9. doi: 10.1016/j.jhep.2004.02.007.

    PMID: 15158341BACKGROUND

  • Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, Shafran SD, Barange K, Lin A, Soman A, Zeuzem S; ACCELERATE Investigators. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34. doi: 10.1056/NEJMoa066403.

    PMID: 17625124BACKGROUND

  • Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004 Apr;39(4):1147-71. doi: 10.1002/hep.20119. No abstract available.

    PMID: 15057920BACKGROUND

  • Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology. 2004 Dec;40(6):1260-5. doi: 10.1002/hep.20467.

    PMID: 15558712BACKGROUND

  • von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Haussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005 Aug;129(2):522-7. doi: 10.1016/j.gastro.2005.05.008.

    PMID: 16083709BACKGROUND

  • Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17. doi: 10.1056/NEJMoa042608.

    PMID: 15972867BACKGROUND

  • Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007 Apr;56(4):553-9. doi: 10.1136/gut.2006.102558. Epub 2006 Sep 6.

    PMID: 16956917BACKGROUND

  • Liu CH, Huang CF, Liu CJ, Dai CY, Huang JF, Lin JW, Liang CC, Yang SS, Lin CL, Su TH, Yang HC, Chen PJ, Chen DS, Chuang WL, Kao JH, Yu ML. Peginterferon plus weight-based ribavirin for treatment-naive hepatitis C virus genotype 2 patients not achieving rapid virologic response: a randomized trial. Sci Rep. 2015 Jul 1;5:11710. doi: 10.1038/srep11710.

    PMID: 26130141DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2aRibavirin

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

  • Jia-Horng Kao, MD, PhD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Ding-Shinn Chen, MD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Ming-Yang Lai, MD, PhD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Pei-Jer Chen, MD, PhD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Chun-Jen Liu, MD, PhD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Chen-Hua Liu, MD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Shih-Jer Hsu, MD

    National Taiwan University Hospital, Yun-Lin Branch

    PRINCIPAL INVESTIGATOR

  • Chih-Lin Lin, MD

    Taipei City Hospital, Ren-Ai Branch

    PRINCIPAL INVESTIGATOR

  • Cheng-Chao Liang, MD

    Far Eastern Memorial Hospital

    PRINCIPAL INVESTIGATOR

  • Ching-Sheng Hsu, MD

    Buddhist Xindian Tzu Chi General Hospital

    PRINCIPAL INVESTIGATOR

  • Sheng-Shun Yang, MD

    Taichung Veterans General Hospital

    PRINCIPAL INVESTIGATOR

  • Chia-Chi Wang, MD

    Buddhist Xindian Tzu Chi General Hospital

    PRINCIPAL INVESTIGATOR

  • Tai-Chung Tseng, MD

    Buddhist Xindian Tzu Chi General Hospital

    PRINCIPAL INVESTIGATOR

  • Ming-Lung Yu, MD, PhD

    Kaohsiung Medical University

    PRINCIPAL INVESTIGATOR

  • Wan-Long Chuang, MD, PhD

    Kaohsiung Medical University

    PRINCIPAL INVESTIGATOR

  • Chia-Yen Dai, MD, Ms

    Kaohsiung Municipal Hsiao-Kang Hospital

    PRINCIPAL INVESTIGATOR

  • Jee-Fu Huang, MD

    Kaohsiung Municipal Hsiao-Kang Hospital

    PRINCIPAL INVESTIGATOR

  • Chang-Fu Chiu, MD

    Paochien Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 18, 2007

First Posted

September 20, 2007

Study Start

November 1, 2007

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

June 4, 2014

Record last verified: 2014-06

Locations

TW(9)