Study of Nitazoxanide (NTZ) Based New Therapeutic Regimens for Helicobacter Pylori

Study Overview
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Brief Summary
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Current Helicobacter Pylori infection preferred treatment involves; proton pump inhibitor (PPI)-based triple or qudrable regimens. Omeprazole, Amoxicillin, and Clarithromycin is one of a global standard care for confirmed H.pylori infection . Metronidazole (MTZ) is used instead of Amoxicillin or Clarithromycin in cases of allergy or resistance . However, a recent study based on the Maastricht III guidelines, indicated that treatment with a PPI-based triple regimen as first-line therapy will fail in  30% of patients on an intention-to-treat (ITT) basis, and will fail in   50 % of patients who treated with PPI-based triple regimen with Metronidazole. This treatment resistance is also an issue warranting the investigation of other agents. Helicobacter pylori infection has become increasingly resistant to traditional first-line treatment regimens because of emerging antibiotic resistance coupled with poor patient compliance with completing the treatment course that decrease H. pylori eradication rates. So there is a considerable interest in evaluating new antibiotic combinations and regimens .

Detailed Description
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Helicobacter pylori (H.pylori) is a small, Gram-negative spirochete inhabiting the mucous layer overlying the gastric epithelial cells in humans. It is the most common prevalent chronic human bacterial infection and the most common cause of gastritis worldwide;. Furthermore, according to the World Health Organization, HP is classified as a type 1 carcinogen and is the primary cause of peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue lymphomas . Current Helicobacter Pylori infection preferred treatment involves; proton pump inhibitor (PPI)-based triple or qudrable regimens.Omeprazole,Amoxicillin &Clarithromycin is one of a global standard care for confirmed H.pylori infection .Metronidazole (MTZ) is used instead of Amoxicillin or Clarithromycin in cases of allergy or resistance . However, a study by Rokkas , et al., 2008 based on the Maastricht III guidelines, indicated that treatment with a PPI-based triple regimen as first-line therapy will fail in  30% of patients on an intention-to-treat (ITT) basis,and will fail in   50 % of patients who treated with PPI-based triple regimen with Metronidazole.This treatment resistance is also an issue warranting the investigation of other agents . Helicobacter pylori infection has become increasingly resistant to traditional first-line treatment regimens because of emerging antibiotic resistance coupled with poor patient compliance with completing the treatment course that decrease H. pylori eradication rates .So there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide (NTZ) is an antibiotic with microbiological characteristics similar to those of Metronidazole which was sittled as a therapy for intestinal protozoa and helminthic infection,and was studied as an additional therapy with Peg Interferon and Ribavirin for chronic hepatitis C virus (HCV) . In the last few years Nitazoxanide was evaluated as a single agent therapy for H. Pylori infection showing controversed results.. However (NTZ) based regimens were recently studied showing interesting results without the apparent problem of resistance as Metronidazole with nearby cost.Moreover ;Levofloxacin,PPI,NTZ&Doxycycline (LOAD) regimen with very good results in H.pylori infection  90% cure rate..But uptil now there are no actual similar reported trials in Egypt.

Official Title
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Study of Nitazoxanide (NTZ) Based New Therapeutic Regimens for Helicobacter Pylori

Conditions
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Helicobacter-associated Gastritis

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Metronidazole(MTZ)
* Drug: Omeprazole
* Drug: Clarithromycin
* Drug: Levofloxacin
* Drug: Doxicycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients with dyspeptic symptoms undergoing upper Gasto-intestinal tract (GIT) endoscopy selecting HP infected patients to be recruited for the study. Patients must have had Helicobacter Pylori - induced disease confirmed by endoscopy and HP monoclonal stool antigen. Exclusion Criteria: Previous gastric or duedenal operations or malignancy. Active GIT bleeding. Pregnancy. Previous treatment for HP. Current use of Antiacids ( proton pump inhibitor ( PPI ), H2 receptor antagonist) , anticoagulant, or recent use of antibiotics (within 6 weeks). Allergy to any medication included in the study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: group I<br>Metronidazole(MTZ) 500mg twice daily ,Omeprazole 20 mg twice daily as (Proton Pump Inhibitor (PPI)& Clarithromycin 500 mg twice daily .for 14 days . 40 patients | Drug: Metronidazole(MTZ)<br>* Metronidazole 500 mg twice daily<br>* Other names: Flagyl;Drug: Omeprazole<br>* Omeprazole 20 twice daily<br>* Other names: Omepak. Napizole;Drug: Clarithromycin<br>* KLacid twice daily<br>* Other names: KLacid;|
| Experimental: Group II<br>Nitazoxanide(NTZ)500 mg twice daily ,PPI 20 mg twice daily & Clarithromycin 500 mg twice daily for 14 days. 40 patients. | Drug: Nitazoxanide<br>* Nitazoxanide based treatment regimens as a new treatment regimens for helicobacter pylori infection<br>* Other names: Alenia,parazoxanide,Nitclean;Drug: Clarithromycin<br>* KLacid twice daily<br>* Other names: KLacid;|
| Experimental: Group III<br>Levofloxacin 250 mg once daily,Omeprazole 40mg once daily(PPI),Nitazoxanide (NTZ) 500mg twice daily & Doxicycline 100 mg once daily (LOND). 40 patients | Drug: Nitazoxanide<br>* Nitazoxanide based treatment regimens as a new treatment regimens for helicobacter pylori infection<br>* Other names: Alenia,parazoxanide,Nitclean;Drug: Omeprazole<br>* Omeprazole 20 twice daily<br>* Other names: Omepak. Napizole;Drug: Levofloxacin<br>* Tavanic. Tavacin<br>* Other names: Levofloxacin once daily;Drug: Doxicycline<br>* Vibramycin 100 mg twice daily<br>* Other names: vibramycin. Doxymycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with proven eradication of helicobacter | Number of patients with proven eradication of helicobacter after 6 weeks | 6 weeks |