STEALTHC-2: Study of Nitazoxanide, Peginterferon Alfa-2a and Ribavirin for the Treatment of Hepatitis C

• Sponsor: Romark Laboratories L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00495391
• Collaborator: (none)
• Enrollment: 64
• Locations: 10
• Arms: 2
• Duration (Months): 31.1
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if nitazoxanide in combination with peginterferon alfa-2a and ribavirin is safe and effective in treating chronic hepatitis C in patients that have previously failed to respond to treatment with peginterferon and ribavirin.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Nitazoxanide; Drug: Placebo; Biological: Peginterferon alfa-2a; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase II, Randomized, Double-blind, Placebo-controlled Study of Nitazoxanide in Combination With Peginterferon Alfa-2a and Ribavirin in Patients With Hepatitis C Who Have Failed to Respond to a Prior Course of Peginterferon and Ribavirin
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.	Drug: Nitazoxanide; One oral 500 mg nitazoxanide tablet twice daily for 52 weeks.; Other Names: Alinia ; Biological: Peginterferon alfa-2a; Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.; Other Names: PEGASYS ; Drug: Ribavirin; 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks.; Other Names: COPEGUS
Placebo Comparator: 2 Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.	Drug: Placebo; One oral placebo tablet twice daily for 52 weeks.; Biological: Peginterferon alfa-2a; Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.; Other Names: PEGASYS ; Drug: Ribavirin; 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks.; Other Names: COPEGUS

Outcome Measures

Primary Outcome Measures

1. Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) [24 weeks after end of treatment]

   Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection 24 weeks after the end of treatment. All others were considered non-responders.

Secondary Outcome Measures

1. End of Treatment Response (HCV RNA Below Lower Limit of Detection) [At end of treatment]

   Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection at the end of treatment. All others were considered non-responders.

2. Early Virologic Response (HCV RNA Below Lower Limit of Detection) [After 12 weeks combination treatment]

   Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 12 weeks of combination therapy.

3. Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) [After 4 weeks combination treatment]

   Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 4 weeks of combination therapy.

4. Changes in ALT [From baseline to week 8]

   This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.

5. Changes in ALT [From baseline to week 16]

   This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.

6. Changes in ALT [From baseline to end of treatment]

   This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.

7. Changes in ALT [From baseline to end of follow up]

   This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic hepatitis C genotype 1.

• Failed to respond to ≥12 weeks of peginterferon and ribavirin (<2 log10 drop in Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 12 or detectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 24).

Exclusion Criteria:

• Females of child-bearing age who are either pregnant, breast-feeding or not using birth control and are sexually active.

• Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active.

• Other causes of liver disease including autoimmune hepatitis.

• Transplant recipients receiving immune suppression therapy.

• Screening tests positive for Anti-Hepatitis A Virus Immunoglobulin M Antibody (anti-HAV IgM Ab), Hepatitis B's antigen (HBsAg), Anti-Hepatitis B core antigen Immunoglobulin M Antibody (anti-HBc IgM Ab) or Anti-Human Immunodeficiency Virus Antibody (anti-HIV Ab).

• Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, Child-Turcotte-Pugh (CTP) score >6 or Model for End-stage Liver Disease (MELD) score >8.

• Alcohol consumption of >40 grams per day or an alcohol use pattern that will interfere with the study.

• Absolute neutrophil count <1500 cells/mm3; platelet count <135,000 cells/mm3; hemoglobin <12 g/dL for women and <13 g/dL for men; or serum creatinine concentration ≥1.5 times Upper Limit of Normal (ULN).

• Hypothyroidism or hyperthyroidism not effectively treated with medication.

• Hemoglobin A1C (HgbA1c) >7.5 or history of diabetes mellitus.

• Body Mass Index (BMI) >28.

• History or other clinical evidence of significant or unstable cardiac disease.

• History or other clinical evidence of chronic pulmonary disease associated with functional impairment.

• Serious or severe bacterial infection(s).

• Ulcerative or hemorrhagic/ischemic colitis.

• Pancreatitis.

• History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization.

• History of uncontrolled severe seizure disorder.

• Requires concomitant theophylline or methadone.

• History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids.

• History or other evidence of severe retinopathy or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension.

• Hemoglobinopathies.

• History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Palo Alto Healthcare System	Palo Alto	California	United States	94304
2	Stanford University School of Medicine	Stanford	California	United States	94305
3	Yale University Digestive Diseases	New Haven	Connecticut	United States	06520
4	University of Florida Hepatology	Gainesville	Florida	United States	32610
5	Florida Center for Gastroenterology	Largo	Florida	United States	33777
6	Atlanta Gastroenterology Associates	Atlanta	Georgia	United States	30308
7	Weill Cornell Medical College	New York	New York	United States	10021
8	Nashville Medical Research Institute	Nashville	Tennessee	United States	37205
9	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
10	McGuire VA Medical Center	Richmond	Virginia	United States	23249

Sponsors and Collaborators

• Romark Laboratories L.C.

Investigators

• Principal Investigator: David Nelson, MD, University of Florida Hepatology
• Principal Investigator: Stephen Harrison, MD, Brooke Army Medical Center
• Principal Investigator: Arthur Berman, DO, Florida Center for Gastroenterology
• Principal Investigator: Ronald Pruitt, MD, Nashville Medical Research Institute
• Principal Investigator: Ahmed Aijaz, MD, Stanford University
• Principal Investigator: Ramsey Cheung, MD, VA Palo Alto Health Care System
• Principal Investigator: Ira Jacobson, MD, Weill Medical College of Cornell University
• Principal Investigator: Mitchell Shiffman, MD, McGuire VA Medical Center
• Principal Investigator: Joseph Lim, MD, Yale University Digestive Diseases
• Principal Investigator: Norman Gitlin, MD, Atlanta Gastroenterology Associates

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Romark Laboratories L.C.
• ClinicalTrials.gov Identifier: NCT00495391
• Other Study ID Numbers: RM01-2025
• First Posted: Jul 3, 2007
• Last Update Posted: May 8, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Romark Laboratories L.C.: Hepatitis C, Chronic
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ribavirin; Peginterferon alfa-2a; Nitazoxanide

Study Results

Participant Flow

Recruitment Details	This study recruited patients from 10 study sites in the United States, including a Veterans Administrations hospital.

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Period Title: Overall Study
STARTED	42	22
From Baseline to Week 8	31	20
From Baseline to Week 16	24	11
From Baseline to End of Treatment	6	1
From Baseline to End of Follow up	6	1
COMPLETED	6	1
NOT COMPLETED	36	21

Baseline Characteristics

Arm/Group Title	NTZ+PR	Placebo+PR	Total
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.	Total of all reporting groups
Overall Participants	42	22	64
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	39 92.9%	21 95.5%	60 93.8%
>=65 years	3 7.1%	1 4.5%	4 6.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (8)	53 (6)	53.5 (6.9)
Sex: Female, Male (Count of Participants)
Female	13 31%	8 36.4%	21 32.8%
Male	29 69%	14 63.6%	43 67.2%
Region of Enrollment (participants) [Number]
United States	42 100%	22 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Sustained Virologic Response (HCV RNA Below Lower Limit of Detection)
Description	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection 24 weeks after the end of treatment. All others were considered non-responders.
Time Frame	24 weeks after end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	42	22
Responders	3 7.1%	0 0%
Non-responders	39 92.9%	22 100%

2. Secondary Outcome

Title	End of Treatment Response (HCV RNA Below Lower Limit of Detection)
Description	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection at the end of treatment. All others were considered non-responders.
Time Frame	At end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	42	22
Responders	6 14.3%	1 4.5%
Non-responders	36 85.7%	21 95.5%

3. Secondary Outcome

Title	Early Virologic Response (HCV RNA Below Lower Limit of Detection)
Description	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 12 weeks of combination therapy.
Time Frame	After 12 weeks combination treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	42	22
Responders	3 7.1%	0 0%
Non-responders	39 92.9%	22 100%

4. Secondary Outcome

Title	Rapid Virologic Response (HCV RNA Below Lower Limit of Detection)
Description	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 4 weeks of combination therapy.
Time Frame	After 4 weeks combination treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	42	22
Responders	2 4.8%	0 0%
Non-responders	40 95.2%	22 100%

5. Secondary Outcome

Title	Changes in ALT
Description	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.
Time Frame	From baseline to week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	31	20
Remains Elevated	14 33.3%	8 36.4%
Elevated to Normal	7 16.7%	2 9.1%
Remains Normal	9 21.4%	9 40.9%
Normal to Elevated	1 2.4%	1 4.5%

6. Secondary Outcome

Title	Changes in ALT
Description	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.
Time Frame	From baseline to week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	24	11
Remains Elevated	6 14.3%	2 9.1%
Elevated to Normal	6 14.3%	2 9.1%
Remains Normal	12 28.6%	6 27.3%
Normal to Elevated	0 0%	1 4.5%

7. Secondary Outcome

Title	Changes in ALT
Description	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.
Time Frame	From baseline to end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	6	1
Remains Elevated	0 0%	0 0%
Elevated to Normal	1 2.4%	0 0%
Remains Normal	5 11.9%	1 4.5%
Normal to Elevated	0 0%	0 0%

8. Secondary Outcome

Title	Changes in ALT
Description	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.
Time Frame	From baseline to end of follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ+PR	Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.	Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
Measure Participants	6	1
Remains Elevated	0 0%	0 0%
Elevated to Normal	1 2.4%	0 0%
Remains Normal	4 9.5%	1 4.5%
Normal to Elevated	1 2.4%	0 0%

Adverse Events

Time Frame	2 years, 1 month
Arm/Group Title	NTZ+PR		Placebo+PR
Arm/Group Description	Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Nitazoxanide : One oral 500 mg nitazoxanide tablet twice daily for 52 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.		Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. Ribavirin : 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks. Peginterferon alfa-2a : Weekly injections of 180µg peginterferon alfa-2a for 48 weeks. Placebo : One oral placebo tablet twice daily for 52 weeks.
All Cause Mortality
	NTZ+PR		Placebo+PR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	NTZ+PR		Placebo+PR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/42 (2.4%)		1/22 (4.5%)
Renal and urinary disorders
Pyelonephritis	1/42 (2.4%)	1	0/22 (0%)	0
Kidney Calculus	1/42 (2.4%)	1	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Edema Larynx	0/42 (0%)	0	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	NTZ+PR		Placebo+PR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/42 (100%)		20/22 (90.9%)
Blood and lymphatic system disorders
Leukopenia	20/42 (47.6%)	20	8/22 (36.4%)	8
Thrombocytopenia	12/42 (28.6%)	12	3/22 (13.6%)	3
Anemia	11/42 (26.2%)	11	5/22 (22.7%)	5
Gastrointestinal disorders
Pain Abdo	9/42 (21.4%)	9	2/22 (9.1%)	2
Diarrhea	17/42 (40.5%)	17	3/22 (13.6%)	3
Nausea	10/42 (23.8%)	10	4/22 (18.2%)	4
Anorexia	6/42 (14.3%)	6	1/22 (4.5%)	1
Constip	5/42 (11.9%)	5	2/22 (9.1%)	2
Liver Func Abnorm	4/42 (9.5%)	4	1/22 (4.5%)	1
Dry Mouth	1/42 (2.4%)	1	3/22 (13.6%)	3
General disorders
Asthenia	23/42 (54.8%)	23	10/22 (45.5%)	10
Headache	9/42 (21.4%)	9	6/22 (27.3%)	6
Pain Back	6/42 (14.3%)	6	0/22 (0%)	0
Flu Synd	5/42 (11.9%)	5	2/22 (9.1%)	2
Metabolism and nutrition disorders
Albuminuria	6/42 (14.3%)	6	3/22 (13.6%)	3
Musculoskeletal and connective tissue disorders
Myalgia	7/42 (16.7%)	7	2/22 (9.1%)	2
Arthralgia	4/42 (9.5%)	4	0/22 (0%)	0
Cramps Leg	4/42 (9.5%)	4	0/22 (0%)	0
Nervous system disorders
Agitation	12/42 (28.6%)	12	6/22 (27.3%)	6
Depression	8/42 (19%)	8	5/22 (22.7%)	5
Insomnia	8/42 (19%)	8	4/22 (18.2%)	4
Anxiety	1/42 (2.4%)	1	4/22 (18.2%)	4
Dizziness	7/42 (16.7%)	7	3/22 (13.6%)	3
Renal and urinary disorders
Polyuria	5/42 (11.9%)	5	2/22 (9.1%)	2
Respiratory, thoracic and mediastinal disorders
Pharyngitis	6/42 (14.3%)	6	1/22 (4.5%)	1
Rhinitis	4/42 (9.5%)	4	3/22 (13.6%)	3
Dyspnea	3/42 (7.1%)	3	3/22 (13.6%)	3
Cough Inc	3/42 (7.1%)	3	3/22 (13.6%)	3
Skin and subcutaneous tissue disorders
Rash	9/42 (21.4%)	9	5/22 (22.7%)	5
Skin Dry	7/42 (16.7%)	7	2/22 (9.1%)	2
Pruritus	5/42 (11.9%)	5	2/22 (9.1%)	2
Alopecia	4/42 (9.5%)	4	3/22 (13.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Presentation and/or publication is encouraged provided the Sponsor is notified in advance and given the opportunity to review the manuscript or abstract 30 days prior to its submission for presentation at a scientific meeting or for publication in a scientific journal. The investigators will have complete autonomy regarding the content and wording including the decision of whether or not to publish.