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

Phase 3

• Conditions: Helicobacter-associated Gastritis
• Interventions: Drug: Metronidazole(MTZ); Drug: Nitazoxanide; Drug: Omeprazole; Drug: Clarithromycin; Drug: Levofloxacin; Drug: Doxicycline

• Registration Number: NCT02422706
• Lead Sponsor: Sherief Abd-Elsalam

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-04-13
• Study First Submitted QC: 2015-04-20
• Study First Posted: 2015-04-21
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-23
• Last Update Posted: 2017-04-25
• Primary Completion: 2018-12
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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

1. Previous gastric or duedenal operations or malignancy.
2. Active GIT bleeding.
3. Pregnancy.
4. Previous treatment for HP.
5. Current use of Antiacids ( proton pump inhibitor ( PPI ), H2 receptor antagonist) , anticoagulant, or recent use of antibiotics (within 6 weeks).
6. Allergy to any medication included in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
group I	Metronidazole(MTZ)	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
group I	Omeprazole	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
group I	Clarithromycin	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
Group II	Nitazoxanide	Nitazoxanide(NTZ)500 mg twice daily ,PPI 20 mg twice daily \& Clarithromycin 500 mg twice daily for 14 days. 40 patients.
Group II	Clarithromycin	Nitazoxanide(NTZ)500 mg twice daily ,PPI 20 mg twice daily \& Clarithromycin 500 mg twice daily for 14 days. 40 patients.
Group III	Nitazoxanide	Levofloxacin 250 mg once daily,Omeprazole 40mg once daily(PPI),Nitazoxanide (NTZ) 500mg twice daily \& Doxicycline 100 mg once daily (LOND). 40 patients
Group III	Omeprazole	Levofloxacin 250 mg once daily,Omeprazole 40mg once daily(PPI),Nitazoxanide (NTZ) 500mg twice daily \& Doxicycline 100 mg once daily (LOND). 40 patients
Group III	Levofloxacin	Levofloxacin 250 mg once daily,Omeprazole 40mg once daily(PPI),Nitazoxanide (NTZ) 500mg twice daily \& Doxicycline 100 mg once daily (LOND). 40 patients
Group III	Doxicycline	Levofloxacin 250 mg once daily,Omeprazole 40mg once daily(PPI),Nitazoxanide (NTZ) 500mg twice daily \& Doxicycline 100 mg once daily (LOND). 40 patients

Primary Outcome Measures

Name	Time	Method
Number of patients with proven eradication of helicobacter	6 weeks	Number of patients with proven eradication of helicobacter after 6 weeks

Trial Locations

Locations (1)

Tanta university hospital; 🇪🇬 Cairo, Egypt