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HIV InfectionPhase 2NCT00991289

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

A Phase 2 study testing Nitazoxanide (NTZ), Pegylated interferon alfa-2a (PEG) and Ribavirin (RBV) in people with HIV Infection and Hepatitis C Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 18 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Infection with hepatitis C virus (HCV) can cause liver scarring, or cirrhosis, and this usually occurs more rapidly among people infected with both HCV and human immunodeficiency virus (HIV). People infected with both HCV and HIV have poor response to the current HCV treatments. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Infection, Hepatitis C Infection
What is being tested?
Nitazoxanide (NTZ), Pegylated interferon alfa-2a (PEG) and Ribavirin (RBV)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
18 sitesin 2 countries
Study dates
Jan 2010to Jan 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HIV-1 infection
  • Documentation of hepatitis C virus (HCV) genotype 1 infection prior to entry
  • Chronic HCV infection for at least 180 days
  • CD4+ cell count greater than 200 cells/mm3 obtained within 90 days prior to study entry
  • Detectable HCV viral load obtained within 90 days prior to study entry
  • Any change in antiretroviral (ARV) regimen, including initiation of antiretroviral therapy (ART), a switch in ART regimen, or a discontinuation of ART, had to have occurred more than 60 days prior to study entry. Breaks in therapy for a maximum of 14 days total during the 60-day period were allowed. Participants not on ART should have had no plans to initiate therapy during the first 24 weeks after study entry. Participants who did start ART did not have to discontinue study treatment. Participants on ART should have planned to remain on the same therapy for at least 12 weeks after study entry. Changes in formulation or dosage were permitted.
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  • Certain laboratory values obtained within 42 days prior to study entry
  • Agreement to use contraception, if participating in sexual activity that could lead to pregnancy, for the duration of study and for 6 months afterward
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase less than or equal to five times the upper limit of normal (ULN)
  • Hemoglobin >=11 g/dl for men and >=10 g/dl for women

Who cannot join

  • Use of the ARV didanosine (ddI)
  • Receipt of any interferon
  • Receipt of any therapy for HCV, including ribavirin (RBV) or experimental treatment
  • Decompensated cirrhosis
  • Currently active or other known causes of significant liver disease, including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygous alpha-1 antitrypsin deficiency
  • Pregnancy or breastfeeding
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  • Men with pregnant sexual partners or men planning pregnancy with any sexual partner during treatment or for 24 weeks after treatment completion
  • Uncontrolled or active depression, other psychiatric disorder, or any hospitalization within the past 52 weeks that, in the opinion of the site investigator, would prevent participation
  • Prior suicide attempt
  • Active thyroid disease (use of thyroid hormone replacement therapy permitted if thyroid stimulating hormone [TSH] or free thyroxine [T4] in the normal range)
  • History of autoimmune processes, including Crohn's disease, ulcerative colitis, severe psoriasis, or rheumatoid arthritis, that may be exacerbated by interferon use
  • Systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
  • Serious illness, including malignancy or active coronary artery disease, within 24 weeks prior to study entry
  • Chronic medical condition that, in the site investigator's opinion, might preclude completion of the protocol
  • Presence of acute or active opportunistic infections within 24 weeks prior to study entry
  • Evidence of hepatocellular carcinoma (HCC) or alpha-fetoprotein level of greater than 50 ng/ml unless an imaging procedure (e.g., computed tomography [CT] scan or magnetic resonance imaging [MRI]) showed no evidence of a hepatic tumor. Each may have been obtained up to 24 weeks before study entry.
  • History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency toward hemolysis
  • History of major organ transplantation with an existing functional graft
  • Known allergy, sensitivity, or any hypersensitivity to components of study drugs or their formulations
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

United States17 sites

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294-2050

  • Massachusetts General Hospital CRS (MGH CRS)

    Boston, Massachusetts, 02114

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27514

  • Cincinnati Clinical Research Site

    Cincinnati, Ohio, 45267-0405

  • MetroHealth CRS

    Cleveland, Ohio, 44109

  • UCLA CARE Center CRS

    Los Angeles, California, 90035

  • Weill Cornell Chelsea CRS

    New York, New York, 10011

  • Columbia P&S CRS

    New York, New York, 10032

  • New Jersey Medical School- Adult Clinical Research Ctr. CRS

    Newark, New Jersey, 07103

  • Stanford AIDS Clinical Trials Unit CRS

    Palo Alto, California, 94304-5350

  • Penn Therapeutics, CRS

    Philadelphia, Pennsylvania, 19104

  • The Miriam Hospital Clinical Research Site (TMH CRS) CRS

    Providence, Rhode Island, 02906

  • Virginia Commonwealth Univ. Medical Ctr. CRS

    Richmond, Virginia, 23298

  • Trillium Health ACTG CRS

    Rochester, New York, 14607

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • UCSD Antiviral Research Center CRS

    San Diego, California, 92103

  • Ucsf Hiv/Aids Crs

    San Francisco, California, 94110

Other trials in United States

Puerto Rico1 site

  • Puerto Rico AIDS Clinical Trials Unit CRS

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: The Activity of Nitazoxanide in Addition to Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C Treatment-Naive Genotype 1 Subjects With HIV Coinfection

Infection with hepatitis C virus (HCV) can cause liver scarring, or cirrhosis, and this usually occurs more rapidly among people infected with both HCV and human immunodeficiency virus (HIV). People infected with both HCV and HIV have poor response to the current HCV treatments. This phase II pilot study evaluated whether adding a new HCV medication improves response to the current standard HCV treatment with pegylated interferon and ribavirin in people with both HCV and HIV.

Read the detailed description

Chronic hepatitis C virus (HCV) is a significant cause of liver scarring, or cirrhosis, and accounts for up to 30% of all liver transplants in the United States. People infected with HIV are at a high risk of coinfection with HCV, and the combination of these two infections appears to accelerate progression to cirrhosis. Current treatment for HCV infection includes a 48-week course of two medications taken together, peginterferon alfa-2a (PEG) and ribavirin (RBV). This combination is only effective in 14% to 29% of people infected with both HIV and HCV genotype 1 (the genotype most common in the United States). Further complicating treatment, antiretrovirals (which are used to treat HIV) and HCV medications can often have high toxicity when taken together, limiting dosing.

Nitazoxanide (NTZ) is a medication currently approved to treat intestinal infections that is being investigated for use in treating HCV. NTZ has few side effects and has been shown to increase effectiveness of HCV treatment when combined with PEG and RBV among HCV monoinfected people. This study will test whether adding NTZ to PEG+RBV regimen for people coinfected with HCV and HIV improves HCV treatment outcomes.

Participation in this study will last up to 76 weeks. At study entry, participants completed a brief physical exam, provided a urine sample for a routine safety test, provided a blood sample, and completed a pregnancy test. Participants then initiated NTZ, which they took twice a day with food for up to a year. After 4 weeks on NTZ, participants completed the second study visit, at which they completed the same assessments as at study entry and were asked about the medications they were taking. At this visit, participants initiated the other two study drugs, PEG and RBV. PEG was delivered via injection weekly and RBV was taken orally twice a day with dose dependent on participant's weight at entry.

Participants took NTZ, PEG and RBV together for up to 48 weeks. During this time, participants completed study visits every 4 weeks until Week 52 and then completed follow-up visits at Weeks 64 and 76. At these visits, participants completed the same assessments as at previous visits, and, at certain weeks, also fasted for 8 hours before blood draw. Additional blood samples were collected and stored at Weeks 4, 8, 16, 52 and 76 in order to do future testing.

Participants who did not achieve an early virologic response to the study treatment (at least a 2-log10 decrease in HCV viral load or undetectable HCV viral load at Week 16), or had detectable HCV viral load at Week 28), stopped study treatment and discontinued study early, at about 20 or 32 weeks, respectively.

Being tested
Nitazoxanide (NTZ), Pegylated interferon alfa-2a (PEG), Ribavirin (RBV)
Keywords
Hepatitis C genotype 1, HCV treatment naive, HCV/HIV coinfection, Antiretroviral, Ribavirin, Pegylated Interferon alfa, Nitazoxanide
Medical subject headings
HIV Infections, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nitazoxanide (NTZ)Drug

    Also called Alinia

    500 mg twice daily, taken orally with food

  • Pegylated interferon alfa-2a (PEG)Drug

    Also called Pegasys

    180 micrograms via subcutaneous injection once weekly

  • Ribavirin (RBV)Drug

    Also called Copegus

    Weight-based dosing; 1,000 mg daily, taken orally, for people weighing less than 75 kg or 1,200 mg for people weighing at least 75 kg.

Study groups in NCT00991289
Study groupRoleWhat they receive
NTZ/PEG/RBVExperimentalParticipants received nitazoxanide (NTZ) alone for 4 weeks followed by 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.
Receives: Drug: Nitazoxanide (NTZ); Drug: Pegylated interferon alfa-2a (PEG); Drug: Ribavirin (RBV)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Complete Early Virologic Response (cEVR)

    Complete early virologic response (cEVR) was defined as undetectable HCV viral load (<43 IU/ml) at week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).

    Measured: Week 16

  2. Percentage of Participants With Early Virologic Response (EVR)

    Early virologic response (EVR) was defined as undetectable HCV viral load (<43 IU/ml) at Week 16 or at least a 2-log10 decrease in HCV viral load from study entry at Week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).

    Measured: Weeks 0, 16

Secondary outcomes (9)

  1. Percentage of Participants With Sustained Virologic Response (SVR)

    Sustained virologic response (SVR) was defined as undetectable HCV viral load (<43 IU/ml) at 24 weeks after treatment discontinuation, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test). Participants who failed to achieve EVR or had detectable HCV RNA at Week 28 and per protocol discontinued study, and participants without HCV RNA from 24 weeks after treatment discontinuation, were considered non-responders.

    Measured: 24 weeks after treatment discontinuation

  2. Percentage of Participants With Rapid Virologic Response (RVR)

    Rapid virologic response (RVR) was defined as undetectable HCV viral load (<43 IU/ml) at Week 8 where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).

    Measured: Week 8

  3. Number of Participants With Adverse Events of Grade 2 or Higher

    Number of participants who experienced an adverse event of Grade 2 or higher at any time after study entry. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.

    Measured: From study entry to up to week 76

  4. Change in Hemoglobin Level From Study Entry

    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.

    Measured: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76.

  5. Percent Change in Fasting Insulin Level From Study Entry

    Percent Change in fasting insulin (FINS) was calculated as FINS at later time point (16, 28, 52, 76) minus FINS at study entry, divided by FINS at study entry x 100%. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting insulin testing.

    Measured: Weeks 0, 16, 28, 52, and 76

  6. Percent Change in Fasting Glucose Level From Study Entry

    Percent Change in fasting glucose (FGLUC) was calculated as FGLUC at later time point (16, 28, 52, 76) minus FGLUC at study entry, divided by FGLUC at study entry x 100%. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting glucose testing.

    Measured: Weeks 0, 16, 28, 52, and 76

  7. Percent Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Study Entry

    HOMA-IR was calculated as [fasting glucose (mg/dL) x fasting insulin (uIU/mL)]/405. Percent Change in HOMA-IR was calculated as HOMA-IR at later time point (16, 28, 52, 76) minus HOMA-IR at study entry, divided by HOMA-IR at study entry x 100%. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting insulin and fasting glucose testing.

    Measured: Weeks 0, 16, 28, 52, and 76

  8. Change in log10 HCV Viral Load After 4 Weeks of Nitazoxanide (NTZ) Monotherapy.

    Change in log10 HCV viral load was calculated as log10-transformed HCV viral load at Week 4 minus log10-transformed HCV viral load at study entry. HCV viral load testing was done using Cobas AmpliPrep/Taqman HCV Test.

    Measured: Weeks 0, 4

  9. Number of Participants With HCV Genotype 1

    Confirmatory HCV genotyping was performed on stored plasma from entry using VERSANT HCV Genotype assay v2.0 (LiPA, RUO, Siemens Healthcare Diagnostics Inc., Tarrytown, NY).

    Measured: Week 0

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2009 (estimated)
  2. Study startJan 2010
  3. Primary completionNov 2010
  4. Study completionJan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00991289
Sponsor's protocol ID
A5269
Other IDs
10764, ACTG A5269
Status last verified
Jan 2019
First submitted
7 Oct 2009
Last updated
4 Nov 2021
Data monitoring committee
Yes

Publications

  • Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB. Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin. Gastroenterology. 2009 Mar;136(3):856-62. doi: 10.1053/j.gastro.2008.11.037. Epub 2008 Nov 19.

    PubMed 19135998

  • Korba BE, Montero AB, Farrar K, Gaye K, Mukerjee S, Ayers MS, Rossignol JF. Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Res. 2008 Jan;77(1):56-63. doi: 10.1016/j.antiviral.2007.08.005. Epub 2007 Sep 4.

    PubMed 17888524

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nitazoxanide (NTZ), Pegylated interferon alfa-2a (PEG) and Ribavirin (RBV) in people with HIV Infection and Hepatitis C Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 18 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Sep 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Complete Early Virologic Response (cEVR) (time frame: Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00991289, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.

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