Ignite Creation Date:
2024-05-06 @ 7:39 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06088316
Status:
RECRUITING
Last Update Posted:
2023-10-18
First Post:
2023-10-12
Brief Title:
Efficacy of Amoxicillin-Esomeprazole HDDT Compared to Levofloxacin Triple Therapy for H Pylori Eradication A RCT
Sponsor:
Bangabandhu Sheikh Mujib Medical University Dhaka Bangladesh
Organization:
Bangabandhu Sheikh Mujib Medical University Dhaka Bangladesh
Study Overview
Official Title:
Efficacy of Amoxicillin-Esomeprazole High Dose Dual Therapy Compared to Levofloxacin Containing Triple Therapy for the Eradication of Helicobacter Pylori in a Tertiary Care Hospital A Single-blind Randomized Controlled Trial
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to compare the efficacy of two different therapeutic regimen for the treatment of Helicobacter pylori infected dyspeptic patients The aim is -
1 To identify the percentage of H pylori infection among dyspeptic patients
2 To compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for the eradication of Helicobacter pylori
Participants will be screened on the basis of two different test stool antigen test endoscopy with rapid urease test to detect H pylori infection Who are positive on both tests will be finally enrolled in the study and randomized into two groups one group will receive amoxicillin esomeprazole for 14 days in higher dose The other group will receive amoxicillin levofloxacin esomeprazole for 14 days in usual dose
Dyspeptic symptoms will be recorded before after treatment Side effects of drugs will also be recorded Finally 1 month after completion of treatment Hpylori status will be cheeked by stool antigen test and results will be compared between two groups
1 To identify the percentage of H pylori infection among dyspeptic patients
2 To compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for the eradication of Helicobacter pylori
Participants will be screened on the basis of two different test stool antigen test endoscopy with rapid urease test to detect H pylori infection Who are positive on both tests will be finally enrolled in the study and randomized into two groups one group will receive amoxicillin esomeprazole for 14 days in higher dose The other group will receive amoxicillin levofloxacin esomeprazole for 14 days in usual dose
Dyspeptic symptoms will be recorded before after treatment Side effects of drugs will also be recorded Finally 1 month after completion of treatment Hpylori status will be cheeked by stool antigen test and results will be compared between two groups
Detailed Description:
Introduction
Helicobacter pylori infection is one of the most common infections worldwide and represents a major cause of gastritis gastric and duodenal ulcers mucosa-associated lymphoid tissue lymphoma Moreover H pylori is recognized as a class 1 carcinogen by the International Agency for Research on cancer WHO It is the most important risk factor for developing gastric cancer the timely elimination of which could lead to a 75 reduction in risk
H pylori infection higher in developing countries as compared to industrially developed countries and the prevalence varies between populations and between groups within the same populationAccording to a recent meta-analysis Bangladesh has the highest prevalence of H pylori infection among Asian countries86
H pylori antimicrobial resistance is an urgent global issue In addition to clarithromycin resistance to metronidazole and fluoroquinolones has also increased worldwide A recent study in Bangladesh showed clarithromycin metronidazole levofloxacin resistance at 393 946 and 661 respectively On the contrary amoxicillin resistance is quite low 36
Since its discovery various H pylori eradication regimens have been investigated around the world with variable efficacy Recent Maastrichts VI guideline recommends susceptibility testing before prescribing 1st line treatment if possible Otherwise bismuth or non-bismuth quadruple therapy followed by levofloxacin containing triple or quadruple therapy for 14 day is recommended for the treatment of H pylori Although these treatment regimens provide acceptable H pylori eradication rates dual triple resistance to antibiotics adversely affects efficacy of these regimens Moreover these regimens can promote resistance due to prolonged therapy with multiple antibiotics A new strategy that can eradicate H pylori as well as reduce the antibiotic exposure is required to prevent future antimicrobial resistance
Amoxicillin is a beta-lactam antibiotic that inhibits cell wall synthesis of actively replicating cells and acts in a time-dependent manner meaning the more time plasma amoxicillin level remains above MIC better the efficacy So increasing dosing frequency enhances the bactericidal action of amoxicillin PPI reduces intra-gastric acidity Increasing the dosing frequency of PPI maintains acid suppression effectively over 24hour period This promotes H pylori replication facilitates amoxicillin action High dose dual therapy with esomeprazole and amoxicillin could be an alternative for H pylori eradication in an era of growing antimicrobial resistanceFor this reason this study was designed to compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for the eradication of H pylori
Research Question
Is amoxicillin-esomeprazole high dose dual therapy non-inferior to levofloxacin containing triple therapy for eradication of Helicobacter pylori
General objective
To compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for the eradication of Helicobacter pylori in a tertiary care hospital
Specific objectives
1 To identify H pylori infection on the basis of stool antigen test rapid urease test among dyspeptic patients
2 To identify H pylori status on the basis of stool antigen test 4 weeks after amoxicillin- esomeprazole high dose dual therapy
3 To identify H pylori status on the basis of stool antigen test 4 weeks after levofloxacin containing triple therapy
4 To assess the efficacy of amoxicillin-esomeprazole high dose dual therapy for H pylori eradication
5 To assess the efficacy of levofloxacin containing triple therapy for H pylori eradication
6 To compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for H pylori eradication
Study design single-blind randomized controlled trial
Study population Patients with dyspeptic symptoms attending the outpatient department of Gastroenterology BSMMU-Dhaka meeting inclusion exclusion criteria
Inclusion criteria
1 Age 18 years
2 Dyspeptic patients with positive Rapid urease test stool antigen test
3 patients giving written informed consent
Exclusion criteria
1 Treatment with proton pump inhibitor H2-receptor antagonist bismuth preparation within the last 2 weeks or antibiotics within 4 weeks prior to study
2 Previous H pylori eradication therapy
3 Complicated duodenal ulcer patients active bleeding and perforation
4 Patients with regular intake of NSAIDs or steroids
5 Surgery that might affect gastric acid secretion upper GI resection or vagotomy
6 Known case of malignancy
7 Advanced Co-morbidities eg CLD CKD cardio-respiratory failure known thyroid disease
8 participants who are pregnant lactating or intend to become pregnant within the duration of the study
Sample size calculation
Numeric Results for Non-Inferiority Tests for the Ratio of Two Proportions Test Statistics Ferrington Manning Likelihood Score Test
Sample sizes of 32 in group 1 and 32 in group 2 achieve 81041 power to detect a non-inferiority margin ratio in the group proportions of 0950 the reference group proportion is 08900 the treatment group proportion is assumed to be 08455 under the null hypothesis of inferiority The power was computed for the case when the actual treatment group proportion is 10000 the test statistic used is the one-sided score testThe significance level of the test is 0050
Considering 10 dropout rate 35 samples will be collected in each group Total sample size will be 70
Data collection
Consecutive Patients with dyspepsia diagnosed on the basis of relevant history will initially be enrolled in the study maintaining inclusion and exclusion criteria from the outpatient department of Gastroenterology BSMMU Fresh stool sample will be collected from all dyspeptic patients in sterile container for stool antigen test Stool antigen test will be carried out by one step chromatographic immunoassay CerTest Biotec SL spain Positive patients of stool antigen test will further undergo endoscopy of upper GIT after proper evaluation ensuring that the patient is fit for endoscopy Endoscopy will be performed by an experienced senior consultant assisted by researcher himself using Olympus GIF-H190 endoscopy machine Any mucosal lesion eg gastritis gastric ulcer duodenal ulcer erosion will be noted in data sheet biopsy one from the antrum one from corpus will be taken for rapid urease test Additional biopsy will also be taken for suspicious looking lesion Rapid urease test will be carried out by RUT media obtained from department of microbiology It will be composed of 40 urea solution 001 neutral red and distilled waterit will be preserved at 37 degrees celsius in an incubator for 24 in the department of microbiology The result will be considered positive when color change from yellow to pink Patients who are positive on both SAT RUT will be finally included in the study Dyspeptic symptoms on a 5-point Likert scale will be recorded at enrolment
Selected 70 patients will then randomly be assigned by computer generated method into two groups- Group A Group B with 35 patients in each group
Group A will receive amoxicillin-esomeprazole high dose dual therapy that is amoxicillin 1gm 8 hourly after meal esomeprazole 40mg 8 hourly 30 minutes before meal for 14 days Group-B patients will receive levofloxacin containing triple therapy that is Levofloxacin 500mg once daily after meal Amoxicillin 1gm 12 hourly after meal Esomeprazole 20mg 12 hourly 30 minutes before meal for 14 days
Patients will be unaware about which group of treatment they are getting but the investigator will know about the treatment allocation
Patients will be followed up at the end of therapy day-14 for drug compliance using drug compliance monitoring card and empty medicine strip for recording of any side effects either in person or over telephone 1 month after completion of therapy fresh stool sample will be collected from all patients for repeat stool antigen test H pylori eradication will be recorded for each group Patients who had mucosal lesion at enrolment will also undergo repeat upper GI endoscopy for re-evaluation of mucosal lesion Dyspeptic symptoms through 5point Likert score will be also recorded for each group 1 month after completion of therapy to cheek for any improvement or not
Statistical analysis
The following steps will be used to analyze the collected data
The entered data will be checked verified and analyzed by IBM SPSS Statistics 25 statistical program for social science software
The data will be presented in tabular figures and diagrammatical form
Appropriate statistical test will be applied for data analysis Numeric data eg Age Likert scale score for dyspepsia will be expressed as mean standard deviation and median range qualitative data eg sex stool antigen test endoscopy upper GIT will be expressed as frequency and percentage
Baseline characteristics of the study patients and outcomes will be evaluated using students t-test ANOVA Chi-square test or Fishers exact test as appropriate Factors influencing the efficacy of the eradication therapy were assessed by univariate multivariate analysis
A P-value less than 005 will be considered as significant at a 95 confidence interval 95 CI
Quality assurance strategy This will be a single blinded randomized control trial Extensive literature review will be done and investigator will be sufficiently trained Inclusion and exclusion criteria will be strictly maintained Every step of the study will be carried out under direct supervision of the guide The completeness and quality of the collected data will be ensured by regular and routine supervision checking and monitoring Guide will randomly scrutinize the data collection procedure Gathered information from patient will be checked and rechecked with medical record Schedule meeting will be arranged with the guide and co-guide regularly to discuss the progress of data collection Data cleaning will be done before editing in the computer for analysis After obtaining results of one quarter of the study subjects review meeting will be arranged with the guide and emerged issue will be addressed properly Before entering data in computer for analysis random checking of 2 of data will be done by the guide Irrelevant and inconsistent data will be discarded After collection of data meeting will be arranged with guide at weekly interval to discuss about the progress of thesis writing and submission
Confidentiality
All the information collected from the patients including the results of the laboratory tests will be kept as confidential under the responsibility of principal investigator No one other than the investigators regulatory authorities and institutional review board committee will have access to such information Patients identity will not be disclosed while analyzing or publishing the results of the study
Helicobacter pylori infection is one of the most common infections worldwide and represents a major cause of gastritis gastric and duodenal ulcers mucosa-associated lymphoid tissue lymphoma Moreover H pylori is recognized as a class 1 carcinogen by the International Agency for Research on cancer WHO It is the most important risk factor for developing gastric cancer the timely elimination of which could lead to a 75 reduction in risk
H pylori infection higher in developing countries as compared to industrially developed countries and the prevalence varies between populations and between groups within the same populationAccording to a recent meta-analysis Bangladesh has the highest prevalence of H pylori infection among Asian countries86
H pylori antimicrobial resistance is an urgent global issue In addition to clarithromycin resistance to metronidazole and fluoroquinolones has also increased worldwide A recent study in Bangladesh showed clarithromycin metronidazole levofloxacin resistance at 393 946 and 661 respectively On the contrary amoxicillin resistance is quite low 36
Since its discovery various H pylori eradication regimens have been investigated around the world with variable efficacy Recent Maastrichts VI guideline recommends susceptibility testing before prescribing 1st line treatment if possible Otherwise bismuth or non-bismuth quadruple therapy followed by levofloxacin containing triple or quadruple therapy for 14 day is recommended for the treatment of H pylori Although these treatment regimens provide acceptable H pylori eradication rates dual triple resistance to antibiotics adversely affects efficacy of these regimens Moreover these regimens can promote resistance due to prolonged therapy with multiple antibiotics A new strategy that can eradicate H pylori as well as reduce the antibiotic exposure is required to prevent future antimicrobial resistance
Amoxicillin is a beta-lactam antibiotic that inhibits cell wall synthesis of actively replicating cells and acts in a time-dependent manner meaning the more time plasma amoxicillin level remains above MIC better the efficacy So increasing dosing frequency enhances the bactericidal action of amoxicillin PPI reduces intra-gastric acidity Increasing the dosing frequency of PPI maintains acid suppression effectively over 24hour period This promotes H pylori replication facilitates amoxicillin action High dose dual therapy with esomeprazole and amoxicillin could be an alternative for H pylori eradication in an era of growing antimicrobial resistanceFor this reason this study was designed to compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for the eradication of H pylori
Research Question
Is amoxicillin-esomeprazole high dose dual therapy non-inferior to levofloxacin containing triple therapy for eradication of Helicobacter pylori
General objective
To compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for the eradication of Helicobacter pylori in a tertiary care hospital
Specific objectives
1 To identify H pylori infection on the basis of stool antigen test rapid urease test among dyspeptic patients
2 To identify H pylori status on the basis of stool antigen test 4 weeks after amoxicillin- esomeprazole high dose dual therapy
3 To identify H pylori status on the basis of stool antigen test 4 weeks after levofloxacin containing triple therapy
4 To assess the efficacy of amoxicillin-esomeprazole high dose dual therapy for H pylori eradication
5 To assess the efficacy of levofloxacin containing triple therapy for H pylori eradication
6 To compare the efficacy of amoxicillin-esomeprazole high dose dual therapy with levofloxacin containing triple therapy for H pylori eradication
Study design single-blind randomized controlled trial
Study population Patients with dyspeptic symptoms attending the outpatient department of Gastroenterology BSMMU-Dhaka meeting inclusion exclusion criteria
Inclusion criteria
1 Age 18 years
2 Dyspeptic patients with positive Rapid urease test stool antigen test
3 patients giving written informed consent
Exclusion criteria
1 Treatment with proton pump inhibitor H2-receptor antagonist bismuth preparation within the last 2 weeks or antibiotics within 4 weeks prior to study
2 Previous H pylori eradication therapy
3 Complicated duodenal ulcer patients active bleeding and perforation
4 Patients with regular intake of NSAIDs or steroids
5 Surgery that might affect gastric acid secretion upper GI resection or vagotomy
6 Known case of malignancy
7 Advanced Co-morbidities eg CLD CKD cardio-respiratory failure known thyroid disease
8 participants who are pregnant lactating or intend to become pregnant within the duration of the study
Sample size calculation
Numeric Results for Non-Inferiority Tests for the Ratio of Two Proportions Test Statistics Ferrington Manning Likelihood Score Test
Sample sizes of 32 in group 1 and 32 in group 2 achieve 81041 power to detect a non-inferiority margin ratio in the group proportions of 0950 the reference group proportion is 08900 the treatment group proportion is assumed to be 08455 under the null hypothesis of inferiority The power was computed for the case when the actual treatment group proportion is 10000 the test statistic used is the one-sided score testThe significance level of the test is 0050
Considering 10 dropout rate 35 samples will be collected in each group Total sample size will be 70
Data collection
Consecutive Patients with dyspepsia diagnosed on the basis of relevant history will initially be enrolled in the study maintaining inclusion and exclusion criteria from the outpatient department of Gastroenterology BSMMU Fresh stool sample will be collected from all dyspeptic patients in sterile container for stool antigen test Stool antigen test will be carried out by one step chromatographic immunoassay CerTest Biotec SL spain Positive patients of stool antigen test will further undergo endoscopy of upper GIT after proper evaluation ensuring that the patient is fit for endoscopy Endoscopy will be performed by an experienced senior consultant assisted by researcher himself using Olympus GIF-H190 endoscopy machine Any mucosal lesion eg gastritis gastric ulcer duodenal ulcer erosion will be noted in data sheet biopsy one from the antrum one from corpus will be taken for rapid urease test Additional biopsy will also be taken for suspicious looking lesion Rapid urease test will be carried out by RUT media obtained from department of microbiology It will be composed of 40 urea solution 001 neutral red and distilled waterit will be preserved at 37 degrees celsius in an incubator for 24 in the department of microbiology The result will be considered positive when color change from yellow to pink Patients who are positive on both SAT RUT will be finally included in the study Dyspeptic symptoms on a 5-point Likert scale will be recorded at enrolment
Selected 70 patients will then randomly be assigned by computer generated method into two groups- Group A Group B with 35 patients in each group
Group A will receive amoxicillin-esomeprazole high dose dual therapy that is amoxicillin 1gm 8 hourly after meal esomeprazole 40mg 8 hourly 30 minutes before meal for 14 days Group-B patients will receive levofloxacin containing triple therapy that is Levofloxacin 500mg once daily after meal Amoxicillin 1gm 12 hourly after meal Esomeprazole 20mg 12 hourly 30 minutes before meal for 14 days
Patients will be unaware about which group of treatment they are getting but the investigator will know about the treatment allocation
Patients will be followed up at the end of therapy day-14 for drug compliance using drug compliance monitoring card and empty medicine strip for recording of any side effects either in person or over telephone 1 month after completion of therapy fresh stool sample will be collected from all patients for repeat stool antigen test H pylori eradication will be recorded for each group Patients who had mucosal lesion at enrolment will also undergo repeat upper GI endoscopy for re-evaluation of mucosal lesion Dyspeptic symptoms through 5point Likert score will be also recorded for each group 1 month after completion of therapy to cheek for any improvement or not
Statistical analysis
The following steps will be used to analyze the collected data
The entered data will be checked verified and analyzed by IBM SPSS Statistics 25 statistical program for social science software
The data will be presented in tabular figures and diagrammatical form
Appropriate statistical test will be applied for data analysis Numeric data eg Age Likert scale score for dyspepsia will be expressed as mean standard deviation and median range qualitative data eg sex stool antigen test endoscopy upper GIT will be expressed as frequency and percentage
Baseline characteristics of the study patients and outcomes will be evaluated using students t-test ANOVA Chi-square test or Fishers exact test as appropriate Factors influencing the efficacy of the eradication therapy were assessed by univariate multivariate analysis
A P-value less than 005 will be considered as significant at a 95 confidence interval 95 CI
Quality assurance strategy This will be a single blinded randomized control trial Extensive literature review will be done and investigator will be sufficiently trained Inclusion and exclusion criteria will be strictly maintained Every step of the study will be carried out under direct supervision of the guide The completeness and quality of the collected data will be ensured by regular and routine supervision checking and monitoring Guide will randomly scrutinize the data collection procedure Gathered information from patient will be checked and rechecked with medical record Schedule meeting will be arranged with the guide and co-guide regularly to discuss the progress of data collection Data cleaning will be done before editing in the computer for analysis After obtaining results of one quarter of the study subjects review meeting will be arranged with the guide and emerged issue will be addressed properly Before entering data in computer for analysis random checking of 2 of data will be done by the guide Irrelevant and inconsistent data will be discarded After collection of data meeting will be arranged with guide at weekly interval to discuss about the progress of thesis writing and submission
Confidentiality
All the information collected from the patients including the results of the laboratory tests will be kept as confidential under the responsibility of principal investigator No one other than the investigators regulatory authorities and institutional review board committee will have access to such information Patients identity will not be disclosed while analyzing or publishing the results of the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None