Chronic Hepatitis cPhase 2/3NCT01276756
Efficacy of Nitazoxanide in the Treatment of Chronic Hepatitis C Virus (HCV)
A Phase 2/3 study testing Pegylated interferon alfa-2a, Nitazoxanide and Ribavirin in people with Chronic Hepatitis c, run by Cairo University at 1 site in Egypt.
Trial summary
Chronic hepatitis C has become an endemic disease in Egypt with a rising prevalence (genotype 4), worldwide it also poses a significant health burden. To date standard of care treatment (pegylated interferon and ribavirin) give modest results with a sustained virological response (SVR) of about 50%. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis c
- What is being tested?
- Pegylated interferon alfa-2a, Nitazoxanide and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- Dec 2010to Nov 2012
- Phase
- Phase 2/3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (male or female), 18 to 65 years of age, with chronic HCV infection
- BMI < 35
- Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system
- Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR (international normalized ratio) no more than 1.5, serum albumin > 3.4, platelet count > 75,000 mm, and no evidence of hepatic decompensation (hepatic encephalopathy or ascites)
- Acceptable hematological and biochemical indices (hemoglobin 13g/dl for men and 12 g/dl for women; neutrophil count 1500/mm3 or more and serum creatinine < 1.5 mg/dl
- Patients must be serum hepatitis B surface antigen (HBsAg) negative
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- Negative Antinuclear Antibodies (ANA) or titer of < 1:160
- Serum positive for anti-HCV antibodies and HCV-RNA
- Abdominal Ultrasound obtained within 3 months prior to entry in the study
- Electrocardiogram for men aged > 40 years and for women aged > 50 years
- Normal fundus examination
- Ensure strict measures to avoid conception for both male and female participants by using a proper contraception measure all throughout the course of treatment and six months later
- Female patients must not breast feed during therapy
Who cannot join
- Patients who previously received interferon
- HgbA1c > 7.5 (glycoslylated haemoglobin)or history of diabetes mellitus
- BMI > 34
- Women who are pregnant or breast-feeding
- 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
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- Transplant recipients receiving immune suppression therapy
- Screening tests positive for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab or anti-HIV Ab
- Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6 (Child-Turcot-Pugh) or MELD score > 8
- 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 ULN (upper limit of normal)
- Hypothyroidism or hyperthyroidism not effectively treated with medication
- Alcohol consumption of > 40 grams per day or an alcohol use pattern that will interfere with the study
- 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)
- 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
- History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids
- Patients with clinically significant retinal abnormalities
- History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Study for the Assessment of Nitazoxanide in the Treatment of Chronic Hepatitis C Genotype 4
Chronic hepatitis C has become an endemic disease in Egypt with a rising prevalence (genotype 4), worldwide it also poses a significant health burden. To date standard of care treatment (pegylated interferon and ribavirin) give modest results with a sustained virological response (SVR) of about 50%. Several pharmaceutical and herbal agents have been used with an aim to improve current results. Recent reports have suggested an increased SVR with the addition of Nitazoxanide to standard of care. The results are preliminary and need to be confirmed. This is a randomized trial to assess the efficacy of nitazoxanide added to standard of care compared to standard of care alone.
- Conditions
- Chronic Hepatitis c
- Being tested
- Pegylated interferon alfa-2a, Nitazoxanide, Ribavirin
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pegylated interferon alfa-2aDrug
Also called Reiferon retard
Pegylated interferon 160ug once weekly 48 weeks
NitazoxanideDrug
Also called Xerovirin-C
Nitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks
RibavirinDrug
Ribavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Active comparator | Group A: comprises 50 treatment-naive chronic hepatitis c patients who will receive the standard of care treatment: peginterferon Alfa 2a 160 ug once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks. Receives: Drug: Pegylated interferon alfa-2a; Drug: Ribavirin |
| Triple therapy | Experimental | Group B: comprises 50 treatment-naive chronic HCV patients who will receive oral Nitazoxanide 500 mg twice daily for 4 weeks (lead-in phase) followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (160ug once weekly) and weight-based ribavirin 1000-1200 mg daily (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks. Receives: Drug: Pegylated interferon alfa-2a; Drug: Nitazoxanide; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Virologic Response
sustained virological response is defined as a negative HCV PCR at 180 days after the end of treatment (End of treatment being at 48 weeks for Group A, 52 weeks for Group B). For any patient who stopped treatment prematurely (e.g. due to adverse events) SVR was defined as a negative HCV PCR (polymerase chain reaction) at 180 days after the last dose of all medications (interferon, ribavirin and nitazoxanide)
Measured: 180 days (+- 7 days) after the end of treatment. (48 weeks for Group A, 52 weeks for Group B, or after the last dose of treatment for patients who stopped prematurely).
Secondary outcomes (4)
Rapid Virological Response
A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment
Measured: 28 - 33 days after start of Pegylated interferon and ribavirin
Early Virological Response
A complete early virologic response is defined as a negative HCV PCR 90 days after the start of pegylated interferon.
A partial early virologic response is defined as a decrease of 2 or more log in HCV PCR at 90 days after the start of pegylated interferon
Measured: 90 ± 7 days from the start of pegylated interferon and ribavirin
End-of-treatment Response
An end-of-treatment response is defined as a negative HCV PCR at 48 weeks after the start of pegylated interferon and ribavirin
Measured: 48 weeks +- 7 days after starting pegylated interferon and ribavirin
Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events)
The occurence of adverse events that could be linked temporally and reasonably to the administration of the tested drug.
Measured: throughout the period of treatment and up to 90 days after end of triple therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startDec 2010
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis cStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Collaborators
- Egyptian Railway Hospital
- Responsible party
- Principal investigator, Hany Shehab, Cairo University
- Investigators
- Hany M Shehab, MD, Principal investigator, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276756
- Sponsor's protocol ID
- RAIL001
- Status last verified
- Mar 2013
- First submitted
- 12 Jan 2011
- Last updated
- 3 May 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Shehab HM, Elbaz TM, Deraz DM. Nitazoxanide plus pegylated interferon and ribavirin in the treatment of genotype 4 chronic hepatitis C, a randomized controlled trial. Liver Int. 2014 Feb;34(2):259-65. doi: 10.1111/liv.12267. Epub 2013 Jul 24.
PubMed 23890273
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study for the Assessment of Nitazoxanide in the Treatment of Chronic Hepatitis C Genotype 4
- ClinicalTrials.gov ID
- NCT01276756
- Acronym / sponsor ID
- RAIL001
- Conditions
- Chronic Hepatitis c
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Collaborators
- Egyptian Railway Hospital
- Study start
- Dec 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 13 Jan 2011 (estimated)
- Results
- Posted 3 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic hepatitis C has become an endemic disease in Egypt with a rising prevalence (genotype 4), worldwide it also poses a significant health burden. To date standard of care treatment (pegylated interferon and ribavirin) give modest results with a sustained virological response (SVR) of about 50%. Several pharmaceutical and herbal agents have been used with an aim to improve current results. Recent reports have suggested an increased SVR with the addition of Nitazoxanide to standard of care. The results are preliminary and need to be confirmed. This is a randomized trial to assess the efficacy of nitazoxanide added to standard of care compared to standard of care alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Active comparator | Drug: Pegylated interferon alfa-2a, Drug: RibavirinGroup A: comprises 50 treatment-naive chronic hepatitis c patients who will receive the standard of care treatment: peginterferon Alfa 2a 160 ug once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks. |
| Triple therapy | Experimental | Drug: Pegylated interferon alfa-2a, Drug: Nitazoxanide, Drug: RibavirinGroup B: comprises 50 treatment-naive chronic HCV patients who will receive oral Nitazoxanide 500 mg twice daily for 4 weeks (lead-in phase) followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (160ug once weekly) and weight-based ribavirin 1000-1200 mg daily (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adult (male or female), 18 to 65 years of age, with chronic HCV infection
- BMI < 35
- Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system
- Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR (international normalized ratio) no more than 1.5, serum albumin > 3.4, platelet count > 75,000 mm, and no evidence of hepatic decompensation (hepatic encephalopathy or ascites)
- Acceptable hematological and biochemical indices (hemoglobin 13g/dl for men and 12 g/dl for women; neutrophil count 1500/mm3 or more and serum creatinine < 1.5 mg/dl
Key exclusion criteria (20 listed)
- Patients who previously received interferon
- HgbA1c > 7.5 (glycoslylated haemoglobin)or history of diabetes mellitus
- BMI > 34
- Women who are pregnant or breast-feeding
- Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pegylated interferon alfa-2aAlso: Reiferon retardPegylated interferon 160ug once weekly 48 weeks | Drug | Standard of care, Triple therapy |
| NitazoxanideAlso: Xerovirin-CNitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks | Drug | Triple therapy |
| RibavirinRibavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks | Drug | Standard of care, Triple therapy |
Primary outcome
Sustained Virologic Response
Time frame: 180 days (+- 7 days) after the end of treatment. (48 weeks for Group A, 52 weeks for Group B, or after the last dose of treatment for patients who stopped prematurely).
sustained virological response is defined as a negative HCV PCR at 180 days after the end of treatment (End of treatment being at 48 weeks for Group A, 52 weeks for Group B). For any patient who stopped treatment prematurely (e.g. due to adverse events) SVR was defined as a negative HCV PCR (polymerase chain reaction) at 180 days after the last dose of all medications (interferon, ribavirin and nitazoxanide)
4 secondary outcomes
Rapid Virological Response
Time frame: 28 - 33 days after start of Pegylated interferon and ribavirin
Early Virological Response
Time frame: 90 ± 7 days from the start of pegylated interferon and ribavirin
End-of-treatment Response
Time frame: 48 weeks +- 7 days after starting pegylated interferon and ribavirin
Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events)
Time frame: throughout the period of treatment and up to 90 days after end of triple therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23890273Shehab HM, Elbaz TM, Deraz DM. Nitazoxanide plus pegylated interferon and ribavirin in the treatment of genotype 4 chronic hepatitis C, a randomized controlled trial. Liver Int. 2014 Feb;34(2):259-65. doi: 10.1111/liv.12267. Epub 2013 Jul 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hany M Shehab, MD principal investigator
Cairo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pegylated interferon alfa-2a, Nitazoxanide and Ribavirin in people with Chronic Hepatitis c, run by Cairo University at 1 site in Egypt.
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 13 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 3 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 May 2013). 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?
Sustained Virologic Response (time frame: 180 days (+- 7 days) after the end of treatment. (48 weeks for Group A, 52 weeks for Group B, or after the last dose of treatment for patients who stopped prematurely).). 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 NCT01276756, which also lists 1 linked publication.
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 3 May 2013.