Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06509139
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
None
First Post:
2024-06-17
Brief Title:
Optimal Duration of Bismuth Quadruple Therapy for Helicobacter Pylori Eradication in Females as Compared With Males
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Optimal Treatment Duration of Bismuth Quadruple Therapy for Helicobacter Pylori Eradication in Female Patients and Comparison of the Efficacy With That of Male Patients
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Helicobacter pylori eradication can reduce the risk of gastric cancer and decrease the recurrence of ulcers However in recent years the increasing antibiotic resistance of Helicobacter pylori has reduced the efficacy of clarithromycin-based triple therapy to below 80 The recent studies including real-world data and a clinical trial have consistently found that females have poorer eradication rate of Helicobacter pylori as compared with males In previous clinical trial investigators discovered that the efficacy of a 10-day bismuth quadruple therapy was not inferior to a 14-day bismuth quadruple therapy However it remains to be investigated whether the 10-day bismuth quadruple therapy is still non-inferior to the 14-day regimen in females
This project continues the clinical trial to investigate whether the efficacy of the 10-day bismuth quadruple therapy in females is inferior to that in males and whether the 14-day bismuth quadruple therapy is superior to the 10-day regimen in females The ultimate goal is to establish that male patients can use the 10-day bismuth quadruple therapy with fewer side effects and without compromising efficacy as compared with the 14-day regimen while female patients are recommended to use the 14-day bismuth quadruple therapy as it would be more effective than the 10-day regimen
Considering sex in research is becoming increasingly important as females have more antibiotic-resistant Helicobacter pylori infection than males The bismuth quadruple therapy can overcome most resistance issues Researching and comparing the difference in the efficacy of bismuth quadruple therapy for Helicobacter pylori eradication between females and males are of significant clinical importance and align with current research trends
This project continues the clinical trial to investigate whether the efficacy of the 10-day bismuth quadruple therapy in females is inferior to that in males and whether the 14-day bismuth quadruple therapy is superior to the 10-day regimen in females The ultimate goal is to establish that male patients can use the 10-day bismuth quadruple therapy with fewer side effects and without compromising efficacy as compared with the 14-day regimen while female patients are recommended to use the 14-day bismuth quadruple therapy as it would be more effective than the 10-day regimen
Considering sex in research is becoming increasingly important as females have more antibiotic-resistant Helicobacter pylori infection than males The bismuth quadruple therapy can overcome most resistance issues Researching and comparing the difference in the efficacy of bismuth quadruple therapy for Helicobacter pylori eradication between females and males are of significant clinical importance and align with current research trends
Detailed Description:
The recently published real-world study on Helicobacter pylori treatment revealing that female odds ratio 241 95 confidence interval CI 116-503 P 002 and age-Charlson Comorbidity Index 2 odds ratio 316 105-948 P 004 were two independent factors for the failure of sequential therapy in eradicating Helicobacter pylori The main cause of eradication failure is antibiotic resistance of the bacteria Previous studies have found that females had more antibiotic-resistant Helicobacter pylori infections as compared with males did In Australia and Italy female was a predictor of metronidazole resistance in Japan and Korea female was a predictor of clarithromycin resistance and among Alaskan Natives and in China female predicted resistance to both metronidazole and clarithromycin
The recent clinical trial found that the efficacy of a 10-day bismuth quadruple therapy was non-inferior to a 14-day bismuth quadruple therapy Intention-to-treat analyses 924 95 CI 882-965 vs 929 95 CI 889-970 absolute difference -06 lower boundary of the one-sided 975 CI -67 P 0020 However subgroup analyses for males and females showed that while the 10-day therapy remained non-inferior to the 14-day therapy in males 952 95 CI 906-998 vs 940 95 CI 884-997 absolute difference 12 lower boundary of the one-sided 975 CI -68 P 0022 it could not be demonstrated as non-inferior in females 892 95 CI 821-963 vs 921 95 CI 865-963 absolute difference -30 lower boundary of the one-sided 975 CI -123 P 0198
Previous research has identified female as a factor in the failure of 7-day clarithromycin-based triple therapy or concomitant therapy for Helicobacter pylori eradication However it is still uncertain whether female is a factor for Helicobacter pylori eradication failure with bismuth quadruple therapy
In recent years analyzing research results separately for females and males has become a trend Historically gender and sex differences were often overlooked in research design conduct and reporting limiting the generalizability and applicability of findings to clinical practice Heidari et al have also advocated for the establishment of basic principles for international guidelines to encourage interdisciplinary research to systematically report sex and gender differences The Sex and Gender Equity in Research SAGER guidelines recommend that researchers provide information on sex and gender in research design data analysis and result interpretation
Given consecutive findings that females may have lower Helicobacter pylori eradication rates than males designing a study to compare the efficacy of different durations of bismuth quadruple therapy between sexes is of significant clinical importance and aligns with current research trends
This study hypothesizes that the rate of antibiotic resistance is higher in females compared to males Consequently the 10-day bismuth quadruple therapy will have a lower eradication rate in females compared to males Because of the higher level of antibiotic resistance females may require a longer treatment duration of 14 days to achieve the optimal eradication rate
The patients with Helicobacter pylori infection are enrolled from National Cheng Kung University Hospital and Tainan Hospital Ministry of Health and Welfare Enrolled male participants received 10-day bismuth quadruple therapy Enrolled female participants were randomly assigned into 10- or 14-day bismuth quadruple therapy with a 11 allocation ratio Females and males are defined by biological attributes based on external body characteristics
Sample size assessment Using a Chi-square test to compare the 10-day bismuth quadruple therapy in females experimental group with the 10-day bismuth quadruple therapy in males control group where the efficacy in the control group is 96 The null hypothesis is that there is no difference in efficacy between the experimental and control groups with a margin of difference set at 7 Helicobacter pylori eradication rate must be at least 90 If the efficacy difference between the two groups is 7 experimental group efficacy 90 the null hypothesis will be rejected indicating a difference between females and males in efficacy of the 10-day bismuth quadruple therapy If the efficacy difference between the two groups is 7 experimental group efficacy 90 the null hypothesis cannot be rejected however there is no evidence to suggest that the 10-day therapy in females is as effective as in males Based on this each group needs 221 patients to achieve 80 power and a two-sided 95 confidence interval to reject the null hypothesis of a 7 difference in efficacy between the two groups
Additionally a superiority trial will compare the 14-day bismuth quadruple therapy in females experimental group with the 10-day bismuth quadruple therapy in females control group where the efficacy in the control group is 89 The null hypothesis is that the experimental group is the same as or worse than the control group with a margin of difference set at 7 past research shows bismuth quadruple therapy efficacy at 96 If the experimental group is superior to the control group with a difference of 7 experimental group efficacy 96 the null hypothesis will be rejected indicating that the 14-day therapy is superior to the 10-day therapy in females If the efficacy difference between the two groups is 7 experimental group efficacy 96 the null hypothesis cannot be rejected however there is no evidence to suggest that the 14-day therapy is as effective as or worse than the 10-day therapy in females Based on this each group needs 219 patients to achieve 80 power and a two-sided 95 confidence interval to reject the null hypothesis of a 7 difference in efficacy between the two groups
Primary Endpoint The primary endpoint of the study is the successful eradication rate of Helicobacter pylori All enrolled participants will be included in the overall analysis incorporating intention-to-treat per-protocol and modified intention-to-treat analyses All enrolled participants are included in the intention-to-treat analysis those who are lost to follow-up take less than 80 of the study medications or have any protocol violation are excluded from the per-protocol analysis The modified intention-to-treat analysis is similar to the intention-to-treat analysis but patients with missing primary outcome data are excluded
Secondary Endpoints The secondary endpoints include the incidence of adverse events and medication adherence There are 14 adverse events recorded including dizziness skin rash headache taste alteration abdominal pain nausea diarrhea constipation bloating vomiting tongue discoloration darkened stool fatigue and anorexia Adverse events are assessed by a physician and a format questionnaire survey after the end of treatment Serious adverse events are defined as daily activities restricted or participant unable to work Medication adherence is assessed using a medication diary to record the number of days the medication was taken
Statistical analysis The statistical analysis is performed with SPSS software SPSS 17 Chicago IL USA The Students t-test Pearsons χ2 test and Mann-Whitney U test are conducted to identify the statistical differences between the two comparison groups
Antibiotic resistance that might affect the eradication rate is assessed by H pylori culture
The recent clinical trial found that the efficacy of a 10-day bismuth quadruple therapy was non-inferior to a 14-day bismuth quadruple therapy Intention-to-treat analyses 924 95 CI 882-965 vs 929 95 CI 889-970 absolute difference -06 lower boundary of the one-sided 975 CI -67 P 0020 However subgroup analyses for males and females showed that while the 10-day therapy remained non-inferior to the 14-day therapy in males 952 95 CI 906-998 vs 940 95 CI 884-997 absolute difference 12 lower boundary of the one-sided 975 CI -68 P 0022 it could not be demonstrated as non-inferior in females 892 95 CI 821-963 vs 921 95 CI 865-963 absolute difference -30 lower boundary of the one-sided 975 CI -123 P 0198
Previous research has identified female as a factor in the failure of 7-day clarithromycin-based triple therapy or concomitant therapy for Helicobacter pylori eradication However it is still uncertain whether female is a factor for Helicobacter pylori eradication failure with bismuth quadruple therapy
In recent years analyzing research results separately for females and males has become a trend Historically gender and sex differences were often overlooked in research design conduct and reporting limiting the generalizability and applicability of findings to clinical practice Heidari et al have also advocated for the establishment of basic principles for international guidelines to encourage interdisciplinary research to systematically report sex and gender differences The Sex and Gender Equity in Research SAGER guidelines recommend that researchers provide information on sex and gender in research design data analysis and result interpretation
Given consecutive findings that females may have lower Helicobacter pylori eradication rates than males designing a study to compare the efficacy of different durations of bismuth quadruple therapy between sexes is of significant clinical importance and aligns with current research trends
This study hypothesizes that the rate of antibiotic resistance is higher in females compared to males Consequently the 10-day bismuth quadruple therapy will have a lower eradication rate in females compared to males Because of the higher level of antibiotic resistance females may require a longer treatment duration of 14 days to achieve the optimal eradication rate
The patients with Helicobacter pylori infection are enrolled from National Cheng Kung University Hospital and Tainan Hospital Ministry of Health and Welfare Enrolled male participants received 10-day bismuth quadruple therapy Enrolled female participants were randomly assigned into 10- or 14-day bismuth quadruple therapy with a 11 allocation ratio Females and males are defined by biological attributes based on external body characteristics
Sample size assessment Using a Chi-square test to compare the 10-day bismuth quadruple therapy in females experimental group with the 10-day bismuth quadruple therapy in males control group where the efficacy in the control group is 96 The null hypothesis is that there is no difference in efficacy between the experimental and control groups with a margin of difference set at 7 Helicobacter pylori eradication rate must be at least 90 If the efficacy difference between the two groups is 7 experimental group efficacy 90 the null hypothesis will be rejected indicating a difference between females and males in efficacy of the 10-day bismuth quadruple therapy If the efficacy difference between the two groups is 7 experimental group efficacy 90 the null hypothesis cannot be rejected however there is no evidence to suggest that the 10-day therapy in females is as effective as in males Based on this each group needs 221 patients to achieve 80 power and a two-sided 95 confidence interval to reject the null hypothesis of a 7 difference in efficacy between the two groups
Additionally a superiority trial will compare the 14-day bismuth quadruple therapy in females experimental group with the 10-day bismuth quadruple therapy in females control group where the efficacy in the control group is 89 The null hypothesis is that the experimental group is the same as or worse than the control group with a margin of difference set at 7 past research shows bismuth quadruple therapy efficacy at 96 If the experimental group is superior to the control group with a difference of 7 experimental group efficacy 96 the null hypothesis will be rejected indicating that the 14-day therapy is superior to the 10-day therapy in females If the efficacy difference between the two groups is 7 experimental group efficacy 96 the null hypothesis cannot be rejected however there is no evidence to suggest that the 14-day therapy is as effective as or worse than the 10-day therapy in females Based on this each group needs 219 patients to achieve 80 power and a two-sided 95 confidence interval to reject the null hypothesis of a 7 difference in efficacy between the two groups
Primary Endpoint The primary endpoint of the study is the successful eradication rate of Helicobacter pylori All enrolled participants will be included in the overall analysis incorporating intention-to-treat per-protocol and modified intention-to-treat analyses All enrolled participants are included in the intention-to-treat analysis those who are lost to follow-up take less than 80 of the study medications or have any protocol violation are excluded from the per-protocol analysis The modified intention-to-treat analysis is similar to the intention-to-treat analysis but patients with missing primary outcome data are excluded
Secondary Endpoints The secondary endpoints include the incidence of adverse events and medication adherence There are 14 adverse events recorded including dizziness skin rash headache taste alteration abdominal pain nausea diarrhea constipation bloating vomiting tongue discoloration darkened stool fatigue and anorexia Adverse events are assessed by a physician and a format questionnaire survey after the end of treatment Serious adverse events are defined as daily activities restricted or participant unable to work Medication adherence is assessed using a medication diary to record the number of days the medication was taken
Statistical analysis The statistical analysis is performed with SPSS software SPSS 17 Chicago IL USA The Students t-test Pearsons χ2 test and Mann-Whitney U test are conducted to identify the statistical differences between the two comparison groups
Antibiotic resistance that might affect the eradication rate is assessed by H pylori culture
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None