Clinical trial NCT04039412: Comparison Between Quadruple Regimens for Helicobacter Pylori Infection in Egypt
Official title: Comparison Between Hybrid, Reverse Hybrid, and Non-Bismuth Levofloxacin Quadruple Regimens for Helicobacter Pylori Infection in Egypt: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Helicobacter Pylori Infection
Keywords: Helicobacter Pylori Infection
Quadruple Therapy
Egypt
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2019-07-31
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized controlled (interventional) study conducted at Zagazig University Hospital, internal medicine department clinic
Primary purpose: TREATMENT

Brief summary: The overall prevalence of H. Pylori in the developing countries is 50.8%, with the highest one presented in Africa (79.1%). Hybrid therapy is supposed to be more effective as a first-line regimen for Helicobacter pylori infection in Egypt than the Reverse hybrid and non-bismuth Levofloxacin quadruple therapies. We are aiming here to compare the Hybrid, Reverse hybrid, and Levofloxacin quadruple therapies as first-line therapy, trying to reach the safest, cost-effective, and compliance-inducing regimen in Egypt. We will conduct a randomized controlled (interventional) study at Zagazig University Hospital, internal medicine department clinic, on 330 patients. 110 patients will be allocated to each regimen.

Detailed description: Introduction:

Although the decreasing prevalence of Helicobacter Pylori (H. Pylori) worldwide, it remains high in developing countries. According to the most recent studies, the overall prevalence of H. Pylori in the developing countries is 50.8%, with the highest one presented in Africa (79.1%).

Unfortunately, the data on the prevalence of H. Pylori, are not available from all the countries of Africa. There is a paucity of information about the magnitude of the problem in Egypt, according to the few available studies, the prevalence is ranging from 71.7-91.7%.

The importance of H. Pylori infection lies in the major role in chronic gastritis, gastric ulcer, and duodenal ulcer, up to gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma.

Diagnosis of H. Pylori can be through invasive tests, which are cumbersome and expensive despite their high sensitivity and specificity. On the contrary, there are more easily and cheaper non-invasive tests, especially H. Pylori stool antigen and urea breath test that has a higher sensitivity than serology.

The decreasing eradication rate of the standard triple therapy (STT) below 80% due to the emergence of resistant strains to Clarithromycin, raise the need for newer therapies that provide higher efficacy, and in the same time, better safety and compliance.

Bismuth-containing quadruple therapy came as the treatment of choice that avoids Clarithromycin use, but it was a non-reasonable option for the countries that are lacking in bismuth salts and/or tetracycline, beside of the complex administration and low safety. It raises the era of the competing sequential and concomitant non-bismuth (clarithromycin containing) quadruple treatments.

A novel two-step (dual-quadruple) treatment called the hybrid therapy (HT), which is actually a combined sequential and concomitant therapy, with a lower cost and better efficacy.

However, the adding of two drugs in the last seven days of the therapy may confuse the patient, making him less willing to complete the treatment that promote the idea of reversing the sequence (quadruple-dual) in what is called the reverse hybrid therapy (RHT), to simplify the treatment in one-step two-phase treatment.

Another non-Clarithromycin non-Bismuth quadruple therapy that is less complex and safer than bismuth quadruple therapy, which is called Levofloxacin quadruple therapy that contains levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOND), showed promising results on the level of the cure rate and low drug resistance profile.

Methods:

Technical Design:

A) The site of study:

The study was conducted in Internal medicine department clinic in Zagazig University Hospitals.

B) Sample size:

Assuming that the eradication rate in patients receiving Hybrid therapy is 91% versus 78.3% in Reverse Hybrid therapy. So, the sample size is 309, using OPEN EPI at power 80% and C.I 95%.

Tools of data collection:

1. Medical history to all participants.
2. Complete clinical examination.
3. The fecal antigen test (FAT) which identifies H. pylori antigen in the stool by enzyme immunoassay was positive in all participants.

Operational design:

A) This is a randomized (interventional) study conducted at Zagazig University Hospital, internal medicine department clinic after informed consent. All the participants were positive for H. pylori fecal antigen test.

B) Steps of performance: (330) participants were chosen from the Internal Medicine Department clinic, grouped into 3 groups:

1. Group 1: (110) participants received reverse hybrid regimen in the form of clarithromycin 500mg bid, omeprazole 20 mg bid, amoxicillin 1gm bid, and metronidazole 500 mg tid for 1 week, followed by omeprazole 20 mg bid, and amoxicillin 1gm bid in the 2nd week.
2. Group2: (110) participants received hybrid regimen in the form of omeprazole 20 mg bid, and amoxicillin 1gm bid in the 1st week, then clarithromycin 500mg bid, omeprazole 20 mg bid, amoxicillin 1gm bid, and metronidazole 500 mg tid in the 2nd week.
3. Group3: (110) participants received Levofloxacin quadruple regimen (LOAD) in the form of nitazoxanide 500 mg bid, levofloxacin 250 mg QD, omeprazole 40 mg QD, and doxycycline 100 mg QD for 10 days

C) Retesting by The fecal antigen test (FAT) after stopping the regimen by at least one month and withholding proton pump inhibitors for four weeks.

Eligibility criteria: Inclusion Criteria:

* Positive Helicobacter pylori antigen in the stool
* Treatment-naive

Exclusion Criteria:

* Previous treatment for Helicobacter pylori
* Drug hypersensitivity

Primary outcomes:
measure: Percentage of Helicobacter Pylori Infection Cure
timeFrame: 40-44 days
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 10-14 days
Secondary outcomes:
measure: Rate of Helicobacter Pylori Treatment Completion
timeFrame: 10-14 days
Other outcomes:
Locations:
city: Zagazig
country: Egypt
facility: Faculty of Human Medicine, Zagazig University
state: Sharkia
Study officials:
affiliation: Zagazig University
name: Ayman MM Sadek, MD
role: STUDY_DIRECTOR
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