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: June 18, 2013
Last verified: June 2013
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. ]

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
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Time Frame From study entry to Week 76.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    NTZ/PEG/RBV  
Total, other (not including serious) adverse events    
# participants affected / at risk     67/67  
Blood and lymphatic system disorders    
Anaemia † 1  
# participants affected / at risk     12/67 (17.91%)  
Neutropenia † 1  
# participants affected / at risk     16/67 (23.88%)  
Gastrointestinal disorders    
Abdominal pain † 1  
# participants affected / at risk     7/67 (10.45%)  
Constipation † 1  
# participants affected / at risk     4/67 (5.97%)  
Diarrhoea † 1  
# participants affected / at risk     18/67 (26.87%)  
Dysphagia † 1  
# participants affected / at risk     4/67 (5.97%)  
Nausea † 1  
# participants affected / at risk     13/67 (19.40%)  
Vomiting † 1  
# participants affected / at risk     6/67 (8.96%)  
General disorders    
Fatigue † 1  
# participants affected / at risk     23/67 (34.33%)  
Irritability † 1  
# participants affected / at risk     4/67 (5.97%)  
Pain † 1  
# participants affected / at risk     5/67 (7.46%)  
Pyrexia † 1  
# participants affected / at risk     5/67 (7.46%)  
Infections and infestations    
Pneumonia bacterial † 1  
# participants affected / at risk     4/67 (5.97%)  
Investigations    
Alanine aminotransferase increased † 1  
# participants affected / at risk     36/67 (53.73%)  
Aspartate aminotransferase increased † 1  
# participants affected / at risk     29/67 (43.28%)  
Blood albumin abnormal † 1  
# participants affected / at risk     7/67 (10.45%)  
Blood alkaline phosphatase increased † 1  
# participants affected / at risk     6/67 (8.96%)  
Blood bicarbonate abnormal † 1  
# participants affected / at risk     5/67 (7.46%)  
Blood bilirubin increased † 1  
# participants affected / at risk     14/67 (20.90%)  
Blood glucose abnormal † 1  
# participants affected / at risk     11/67 (16.42%)  
Blood glucose increased † 1  
# participants affected / at risk     6/67 (8.96%)  
Blood phosphorus decreased † 1  
# participants affected / at risk     14/67 (20.90%)  
Blood potassium decreased † 1  
# participants affected / at risk     6/67 (8.96%)  
Blood sodium decreased † 1  
# participants affected / at risk     9/67 (13.43%)  
Blood triglycerides abnormal † 1  
# participants affected / at risk     4/67 (5.97%)  
Blood uric acid increased † 1  
# participants affected / at risk     11/67 (16.42%)  
Haemoglobin decreased † 1  
# participants affected / at risk     24/67 (35.82%)  
Lipase increased † 1  
# participants affected / at risk     11/67 (16.42%)  
Neutrophil count decreased † 1  
# participants affected / at risk     54/67 (80.60%)  
Platelet count decreased † 1  
# participants affected / at risk     35/67 (52.24%)  
Weight decreased † 1  
# participants affected / at risk     21/67 (31.34%)  
White blood cell count decreased † 1  
# participants affected / at risk     23/67 (34.33%)  
Metabolism and nutrition disorders    
Decreased appetite † 1  
# participants affected / at risk     14/67 (20.90%)  
Musculoskeletal and connective tissue disorders    
Arthralgia † 1  
# participants affected / at risk     5/67 (7.46%)  
Back pain † 1  
# participants affected / at risk     5/67 (7.46%)  
Pain in extremity † 1  
# participants affected / at risk     5/67 (7.46%)  
Nervous system disorders    
Dizziness † 1  
# participants affected / at risk     9/67 (13.43%)  
Headache † 1  
# participants affected / at risk     7/67 (10.45%)  
Psychiatric disorders    
Anxiety † 1  
# participants affected / at risk     5/67 (7.46%)  
Depression † 1  
# participants affected / at risk     9/67 (13.43%)  
Insomnia † 1  
# participants affected / at risk     5/67 (7.46%)  
Respiratory, thoracic and mediastinal disorders    
Cough † 1  
# participants affected / at risk     5/67 (7.46%)  
Dyspnoea † 1  
# participants affected / at risk     7/67 (10.45%)  
Oropharyngeal pain † 1  
# participants affected / at risk     4/67 (5.97%)  
Respiratory tract congestion † 1  
# participants affected / at risk     4/67 (5.97%)  
Skin and subcutaneous tissue disorders    
Alopecia † 1  
# participants affected / at risk     4/67 (5.97%)  
Pruritus † 1  
# participants affected / at risk     4/67 (5.97%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.0



  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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