Clinical trial NCT01683786: 36 vs 48 Wks Peg-Intron Plus Ribavirin for HCV Patients Without Rapid Virologic Response But Without HCV RNA at wk 8
Official title: An Open Label, Randomized, Parallel Design Estimation Pilot Study to Compare the Effectiveness of 36 vs 48 Wks PegIntron Plus Ribavirin Treatment for HCV Patients Without Rapid Virologic Response(RVR) But With Undetectable HCV RNA at wk 8
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis C Infection
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-09-12
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Purpose:

To compare the effectiveness of 36 weeks versus 48 weeks pegintron plus ribavirin treatment for hepatitis C virus(HCV) patients without rapid virologic response(RVR), but with undetectable HCV RNA at wk 8.

Study Design:

a multi-site, prospective, open label, randomized, pilot trial. Approximately 60 HCV Genotype 1 patients who fail to achieve RVR but achieve undetectable HCV RNA at week 8 (\<50 IU/ml) will be recruited into 2 arms(30 in each arm). Patients must receive pegylated interferon-α2b at 1.5 μg/kg of body weight/week and ribavirin 800\~1400 mg/day for 12 wks before entering this study.

Detailed description: Purpose:

To compare the effectiveness of 36 wks versus 48 wks pegintron plus ribavirin treatment for HCV patients without RVR, but with undetectable HCV RNA at wk 8.

Study Design:

This is a multi-site, prospective, open label, randomized, pilot trial. Approximately 60 HCV Genotype 1 patients who fail to achieve RVR at wk 4 but achieve undetectable HCV RNA at wk 8 (\<50 IU/ml) will be recruited into 2 arms(30 in each arm). Patients must receive pegylated IFN-α2b at 1.5 μg/kg of body weight/week and ribavirin 800\~1400 mg/day for 12 wks before entering this study.

Study Duration:

The estimated recruitment period is 12 months; the follow-up duration is 72 weeks (longest treatment period plus 6 month- f/u period); the total study duration (FPE-\>LPLV) is estimated to be 2.5 years

Statistical Analysis and Sample Size Justification:

A. The study is not primarily designed for hypothesis testing; thus the sample size calculation is not based on the primary objective, Approximately 60 subjects (30 in each arm) will be recruited into this study B. For descriptive statistics, the continuous variables will be expressed as mean ± standard deviation, and the categorical variables will be performed the number of cases and the corresponding percentages.

The primary analysis will focus on the efficacy response to the shortened HCV treatment course (36 wks) compared with standard course (48 wks). The between-group difference for efficacy endpoint will be assessed by the difference in the percentage of virologic responder after 24 wks of HCV treatment. For univariate analyses, comparisons of independent samples (shortened vs. standard course) will be assessed with Student's t test. The comparisons of categorical variables will be assessed using the chi-square test. Regarding the multivariate analysis, the proportion of patients achieving virologic responder will be compared among groups using a logistic regression analysis with terms of potential confounding factors. The OR estimates will be derived from the logistic regression model and the corresponding 95% CIs will be used to quantify the each effect of treatment course length and confounding factors.

All randomized patients who take at least one dose of HCV regimen will be included in safety assessment. Fisher's exact test will be used to compare between-group incidences of AEs. For patients with any clinical AEs, treatment related AEs, serious AEs, or discontinuations because of AEs, the data among groups will be provided as well. Statistical significance will be determined at the 0.05 level for all tests.

Eligibility criteria: Inclusion Criteria:

1. Aged 20y/o or older
2. Positive for the HCV antibody and HCV RNA detected with abnormal ALT (≧ 1X) before initiating PegIFN plus RBV treatment
3. HCV Genotype 1
4. Have failed to achieve RVR at week 4 but achieve undetectable HCV RNA at week 8 (\< 50 IU/ml) with PegIFN plus RBV treatment
5. Have received PegIFN plus RBV treatment for 12weeks with good compliance (who have received \>80% of expected PegIFN and RBV doses and completed at least 80% of the expected duration (80/80/80 adherence) and achieve EVR before entering this study

Exclusion Criteria:

1. Subjects with decompensated liver disease or overt cirrhosis by ultrasound.
2. With prior exposures to interferon (standard or pegylated) treatment before baseline.
3. With human immunodeficiency virus
4. With hepatitis B infection
5. With neutrophil count \< 1500 mm3,
6. With platelet count \< 90000 mm3,
7. With hemoglobin level \< 12g/dL for men or \< 11 g/dL for women
8. With serum creatinine level \> 1.5 mg/dL
9. With clinically significant cardiac or cardiovascular abnormalities, organ grafts, systemic infections, clinically significant bleeding disorders, evidence of malignant neoplastic diseases
10. Female patients with pregnancy or lactation. Pregnancy in partners of male patients.
11. Hypersensitive to study drugs cases.

Primary outcomes:
measure: The rate of sustained virologic response
timeFrame: At 24 weeks after end of treatment
Secondary outcomes:
measure: the factors associated with sustained virologic response(SVR) between groups
timeFrame: 24 weeks after the end of treatment
measure: the rate of end-of-treatment response(EOT)
timeFrame: At the end of treatment (36 or 48 weeks of treatment period)
measure: The relapse rate
timeFrame: At 24 weeks after end of treatment
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung Branch
city: Pingtung
country: Taiwan
facility: Pingtung Christian Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center - Liouying Branch
city: Taipei
country: Taiwan
facility: Shin Kong Wu Ho-Su Memorial Hosipital
Study officials:
affiliation: Chang Gung Medical Foundation, Kaohsiung Branch
name: Tsung-Hui Hu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: