Nitazoxanide Plus Ribavirin and Peginterferon for Therapy of Treatment Naive HCV Genotype 1 and HIV Coinfected Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00991289
First received: October 7, 2009
Last updated: August 18, 2014
Last verified: August 2014
Results First Received: August 29, 2011  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV Infection
Hepatitis C Infection
Interventions: Drug: Nitazoxanide (NTZ)
Drug: Pegylated interferon alfa-2a (PEG)
Drug: Ribavirin (RBV)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Men and women at least 18 years of age with genotype 1 hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection and naive to previous HCV treatment were recruited for participation in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
NTZ/PEG/RBV Participants received nitazoxanide (NTZ) alone for 4 weeks followed by up to 48 weeks of NTZ with pegylated interferon (PEG) and ribavirin (RBV). Participants who did not achieve early virologic response (EVR) at Week 16 or had detectable hepatitis C virus (HCV) viral load at Week 28 discontinued treatment.

Participant Flow:   Overall Study
    NTZ/PEG/RBV  
STARTED     67 [1]
COMPLETED Week 16     61 [2]
COMPLETED     55 [3]
NOT COMPLETED     12  
Adverse Event                 1  
Physician Decision                 2  
Withdrawal by Subject                 3  
Lost to Follow-up                 4  
Protocol Violation                 2  
[1] 68 participants enrolled, one was found to have been ineligible and was excluded.
[2] Completed 16 weeks of the study (the primary endpoint time point). The study continued to Week 76.
[3] Completed study.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
NTZ/PEG/RBV Participants received nitazoxanide (NTZ) alone for 4 weeks followed by up to 48 weeks of NTZ with pegylated interferon (PEG) and ribavirin (RBV). Participants who did not achieve early virologic response (EVR) at Week 16 or had detectable hepatitis C virus (HCV) viral load at Week 28 discontinued treatment.

Baseline Measures
    NTZ/PEG/RBV  
Number of Participants  
[units: participants]
  67  
Age  
[units: years]
Mean ± Standard Deviation
  48.1  ± 8.5  
Age, Customized  
[units: participants]
 
<25 years     1  
25 to <30 years     1  
30 to <35 years     4  
35 to <40 years     3  
40 to <45 years     11  
45 to <50 years     13  
50 to <55 years     18  
55 to 60 years     13  
>=60 years     3  
Gender  
[units: participants]
 
Female     15  
Male     52  
Race/Ethnicity, Customized [1]
[units: Participants]
 
White, Non-Hispanic     21  
Black, Non-Hispanic     32  
Hispanic, Regardless of Race     12  
Other/Unknown     2  
Region of Enrollment  
[units: participants]
 
United States     67  
HCV viral load level [2]
[units: log10┬áIU/ml]
Median ( Inter-Quartile Range )
  6.4  
  ( 6.0 to 6.7 )  
CD4+ T cell count  
[units: cells/mm3]
Median ( Inter-Quartile Range )
  452  
  ( 323 to 738 )  
Number of participants with indicated HIV viral load [3]
[units: participant]
 
Undetectable HIV viral load     49  
Detectable HIV viral load     16  
Unknown     2  
HIV Antiretroviral therapy (ART) status  
[units: participant]
 
On ART     61  
Not on ART     6  
[1] Race/ethnicity, self-reported (NIH categories)
[2] Hepatitis C virus (HCV) viral load testing was done using Cobas AmpliPrep/Taqman HCV Test with lower limit of quantitation of 43 IU/ml.
[3] A blood sample was drawn to determine the HIV viral load by local laboratories. HIV viral load was categorized as <lower limit of quantification (undetectable) of the assay or >=lower limit of quantification of the assay (detectable). The assays used were bDNA assay (Versant HIV-1 RNA 3.0), Roche COBAS AmpliPrp/Taqman HIV-1 assay and Abbott RealTime HIV-1 assay.



  Outcome Measures
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1.  Primary:   Percentage of Participants With Complete Early Virologic Response (cEVR)   [ Time Frame: Week 16 ]

2.  Primary:   Percentage of Participants With Early Virologic Response (EVR)   [ Time Frame: Weeks 0, 16 ]

3.  Secondary:   Percentage of Participants With Sustained Virologic Response (SVR)   [ Time Frame: 24 weeks after treatment discontinuation ]

4.  Secondary:   Percentage of Participants With Rapid Virologic Response (RVR)   [ Time Frame: Week 8 ]

5.  Secondary:   Number of Participants With Adverse Events of Grade 2 or Higher   [ Time Frame: From study entry to up to week 76 ]

6.  Secondary:   Change in Hemoglobin Level From Study Entry   [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76. ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Change in Hemoglobin Level From Study Entry
Measure Description Change in hemoglobin (HGB) was calculated as HGB at later time point (Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76) minus HGB at study entry.
Time Frame Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who enrolled, except one participant who was found to have been ineligible after entry, and had HGB measurement available at entry and at the respective post-entry time point: 65, 65, 63, 60, 55, 51, 45, 38, 39, 34, 31, 32, 31 and 29 participants at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 76, respectively.

Reporting Groups
  Description
NTZ/PEG/RBV Participants received nitazoxanide (NTZ) alone for 4 weeks followed by up to 48 weeks of NTZ with pegylated interferon (PEG) and ribavirin (RBV). Participants who did not achieve early virologic response (EVR) at Week 16 or had detectable hepatitis C virus (HCV) viral load at Week 28 discontinued treatment.

Measured Values
    NTZ/PEG/RBV  
Number of Participants Analyzed  
[units: participants]
  67  
Change in Hemoglobin Level From Study Entry  
[units: g/dL]
Median ( Inter-Quartile Range )
 
Change in HGB at Week 4 (n=65)     -0.1  
  ( -0.6 to 0.4 )  
Change in HGB at Week 8 (n=65)     -2.1  
  ( -3.0 to -1.1 )  
Change in HGB at Week 12 (n=63)     -2.5  
  ( -3.5 to -1.8 )  
Change in HGB at Week 16 (n=60)     -2.5  
  ( -3.5 to -1.4 )  
Change in HGB at Week 20 (n=55)     -2.5  
  ( -3.8 to -1.3 )  
Change in HGB at Week 24 (n=51)     -2.4  
  ( -3.2 to -1.3 )  
Change in HGB at Week 28 (n=45)     -2.5  
  ( -3.4 to -1.6 )  
Change in HGB at Week 32 (n=38)     -2.7  
  ( -3.4 to -1.7 )  
Change in HGB at Week 36 (n=39)     -2.5  
  ( -3.9 to -1.7 )  
Change in HGB at Week 40 (n=34)     -2.6  
  ( -3.4 to -2.1 )  
Change in HGB at Week 44 (n=31)     -2.6  
  ( -3.9 to -1.6 )  
Change in HGB at Week 48 (n=32)     -2.7  
  ( -3.4 to -1.9 )  
Change in HGB at Week 52 (n=31)     -2.9  
  ( -3.8 to -1.6 )  
Change in HGB at Week 76 (n=29)     -0.9  
  ( -1.3 to -0.5 )  

No statistical analysis provided for Change in Hemoglobin Level From Study Entry



7.  Secondary:   Percent Change in Fasting Insulin Level From Study Entry   [ Time Frame: Weeks 0, 16, 28, 52, and 76 ]

8.  Secondary:   Percent Change in Fasting Glucose Level From Study Entry   [ Time Frame: Weeks 0, 16, 28, 52, and 76 ]

9.  Secondary:   Percent Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Study Entry   [ Time Frame: Weeks 0, 16, 28, 52, and 76 ]

10.  Secondary:   Change in log10 HCV Viral Load After 4 Weeks of Nitazoxanide (NTZ) Monotherapy.   [ Time Frame: Weeks 0, 4 ]

11.  Secondary:   Number of Participants With HCV Genotype 1   [ Time Frame: Week 0 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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