- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04039412
Comparison Between Quadruple Regimens for Helicobacter Pylori Infection in Egypt
Comparison Between Hybrid, Reverse Hybrid, and Non-Bismuth Levofloxacin Quadruple Regimens for Helicobacter Pylori Infection in Egypt: A Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
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:
- Medical history to all participants.
- Complete clinical examination.
- 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:
- 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.
- 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.
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Sharkia
-
Zagazig, Sharkia, Egypt, 44519
- Faculty of Human Medicine, Zagazig University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Positive Helicobacter pylori antigen in the stool
- Treatment-naive
Exclusion Criteria:
- Previous treatment for Helicobacter pylori
- Drug hypersensitivity
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: (1) Hybrid regimen
omeprazole 20mg bid, and amoxicillin 1gm bid in the 1st week, then clarithromycin 500mg bid, omeprazole 20mg bid, amoxicillin 1gm bid, and metronidazole 500mg tid in the 2nd week.
|
two-step (dual-quadruple) treatment
|
ACTIVE_COMPARATOR: (2) Reverse hybrid regimen
clarithromycin 500mg bid, omeprazole 20mg bid, amoxicillin 1gm bid, and metronidazole 500mg tid for 1 week, followed by omeprazole 20mg bid, and amoxicillin 1gm bid in the 2nd week.
|
one-step two-phase (quadruple-dual) treatment
|
ACTIVE_COMPARATOR: (3) Levofloxacin quadruple regimen
levofloxacin 250mg QD, omeprazole 40mg QD, nitazoxanide 500mg bid, and doxycycline 100mg QD for 10 days.
(LOAD)
|
non-Clarithromycin non-Bismuth quadruple therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Helicobacter Pylori Infection Cure
Time Frame: 40-44 days
|
Measuring the curative rate of each regimen by a fecal antigen test
|
40-44 days
|
Incidence of Treatment-Emergent Adverse Events
Time Frame: 10-14 days
|
Questionnaire to measure the number of Participants with Treatment-Emergent Adverse Events
|
10-14 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Helicobacter Pylori Treatment Completion
Time Frame: 10-14 days
|
Questionnaire to evaluate the compliance with each treatment regimen
|
10-14 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Ayman MM Sadek, MD, Zagazig University
Publications and helpful links
General Publications
- Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012 May;61(5):646-64. doi: 10.1136/gutjnl-2012-302084.
- Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5.
- Torres J, Perez-Perez G, Goodman KJ, Atherton JC, Gold BD, Harris PR, la Garza AM, Guarner J, Munoz O. A comprehensive review of the natural history of Helicobacter pylori infection in children. Arch Med Res. 2000 Sep-Oct;31(5):431-69. doi: 10.1016/s0188-4409(00)00099-0.
- Zamani M, Ebrahimtabar F, Zamani V, Miller WH, Alizadeh-Navaei R, Shokri-Shirvani J, Derakhshan MH. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. 2018 Apr;47(7):868-876. doi: 10.1111/apt.14561. Epub 2018 Feb 12.
- Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017 Aug;153(2):420-429. doi: 10.1053/j.gastro.2017.04.022. Epub 2017 Apr 27.
- El Dine SS, Mubarak M, Salama R, El Raziky M, El Sherbiny E, Zakaria S, Zakaria MS. Low Seroprevalence of anti-CagA antibodies inspite of high seroprevalence of anti-H. Pylori antibodies in rural Egyptian community. Research Journal of Medicine and Medical Sciences. 2008; 3(2):118-23.
- Diab M, El-Dine SS, Aboul-Fadl L, Shemis M, Omran Z, Badawi A, El-Ghannam M, El-Ray A, Fam N, El-Defrawy I, El-Sherbini E. Helicobacterpylori cag pathogenicity island genes among dyspeptic patients with chronic gastritis. Egypt J Med Microbiol. 2009; 18:43-53.
- Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002 Oct 10;347(15):1175-86. doi: 10.1056/NEJMra020542. No abstract available.
- Garza-Gonzalez E, Perez-Perez GI, Maldonado-Garza HJ, Bosques-Padilla FJ. A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication. World J Gastroenterol. 2014 Feb 14;20(6):1438-49. doi: 10.3748/wjg.v20.i6.1438.
- Huang YK, Wu MC, Wang SS, Kuo CH, Lee YC, Chang LL, Wang TH, Chen YH, Wang WM, Wu DC, Kuo FC. Lansoprazole-based sequential and concomitant therapy for the first-line Helicobacter pylori eradication. J Dig Dis. 2012 Apr;13(4):232-8. doi: 10.1111/j.1751-2980.2012.00575.x.
- Georgopoulos SD, Papastergiou V, Karatapanis S. Helicobacter pylori Eradication Therapies in the Era of Increasing Antibiotic Resistance: A Paradigm Shift to Improved Efficacy. Gastroenterol Res Pract. 2012;2012:757926. doi: 10.1155/2012/757926. Epub 2012 Jun 19.
- Liou JM, Fang YJ, Chen CC, Bair MJ, Chang CY, Lee YC, Chen MJ, Chen CC, Tseng CH, Hsu YC, Lee JY, Yang TH, Luo JC, Chang CC, Chen CY, Chen PY, Shun CT, Hsu WF, Hu WH, Chen YN, Sheu BS, Lin JT, Wu JY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2016 Nov 12;388(10058):2355-2365. doi: 10.1016/S0140-6736(16)31409-X. Epub 2016 Oct 18.
- Liatsos C, Georgopoulos SD. Helicobacter pylori best treatment approach: should a national consensus be the best consensus? Ann Gastroenterol. 2017;30(6):704-706. doi: 10.20524/aog.2017.0183. Epub 2017 Aug 2. No abstract available.
- Hsu PI, Tsay FW, Graham DY, Tsai TJ, Tsai KW, Kao JY, Peng NJ, Kuo CH, Kao SS, Wang HM, Lin TF, Wu DC; Taiwan Acid-related Disease (TARD) Study Group. Equivalent Efficacies of Reverse Hybrid and Bismuth Quadruple Therapies in Eradication of Helicobacter pylori Infection in a Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2018 Sep;16(9):1427-1433. doi: 10.1016/j.cgh.2018.03.031. Epub 2018 Mar 31.
- Basu PP, Rayapudi K, Pacana T, Shah NJ, Krishnaswamy N, Flynn M. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol. 2011 Nov;106(11):1970-5. doi: 10.1038/ajg.2011.306. Epub 2011 Oct 11.
- Abd-Elsalam S, Kobtan A, El-Kalla F, Elkhalawany W, Nawasany SE, Saif SA, Yousef M, Ali LA, Soliman S, Mansour L, Habba E, Soliman H, Rizk F, Shehata MA. A 2-week Nitazoxanide-based quadruple treatment as a rescue therapy for Helicobacter pylori eradication: A single center experience. Medicine (Baltimore). 2016 Jun;95(24):e3879. doi: 10.1097/MD.0000000000003879. Erratum In: Medicine (Baltimore). 2016 Aug 07;95(31):e5074.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Disease Attributes
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Infections
- Communicable Diseases
- Helicobacter Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Anti-Infective Agents, Urinary
- Renal Agents
- Levofloxacin
- Ofloxacin
Other Study ID Numbers
- ZU-IRB#5089
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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