Ignite Creation Date:
2024-05-06 @ 1:01 PM
Last Modification Date:
2024-10-26 @ 1:07 PM
Study NCT ID:
NCT03908619
Status:
UNKNOWN
Last Update Posted:
2020-10-08
First Post:
2019-04-05
Brief Title:
A RCT of Triple Therapy With Proton Pump Inhibitor vs Vonoprazan for Helicobacter Pylori Gastritis
Sponsor:
Changi General Hospital
Organization:
Changi General Hospital
Study Overview
Official Title:
A Randomized Controlled Trial of Triple Therapy With Conventional Proton Pump Inhibitor vs Triple Therapy With Vonoprazan as First Line Therapy for Helicobacter Pylori Gastritis
Status:
UNKNOWN
Status Verified Date:
2020-10
Last Known Status:
RECRUITING
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:
TRIVON
Brief Summary:
Helicobacter pylori H pylori gastritis is a common bacterial infection among the elderly population H pylori infection causes chronic progressive gastric inflammation peptic ulcer disease and gastric cancer Gastric cancer is a significant contributor of cancer-related mortality The eradication of H pylori reduces the incidence of gastric cancer However the efficacy of H pylori eradication has decreased dramatically because of antibiotic resistance This study aims to i compare the eradication rates of H pylori by triple therapy with vonoprazan for the treatment of H pylori gastritis TTV regimen with triple therapy with conventional proton pump inhibitor PPI TTP regimen in a multi-racial Asian cohort ii evaluate the prevalence of antibiotic klacidamoxicillinlevofloxacintetracycline resistance in H pylori infected patients and iii assess the safety of the TTV regimen Diagnosed H pylori-infected patients n252 will be enrolled and randomized 11 to TTV or TTP regimen Gastric biopsies will be cultured and antibiotic sensitivity evaluated using E-testagar dilution method The safety of TTV regimen will be assessed using adverse effect questionnaire This study may potentially impact on prescribing policies and management of H pylori infections for improved therapeutic outcome
Detailed Description:
All subjects who present for endoscopy will be screened Consent will be taken from subjects who are scheduled to undergo gastroscopy Gastric biopsies to test for the presence of H pylori using the rapid CLO test and for culture and sensitivity will be obtained Based on an estimated prevalence of H pylori of 20 we aim to screen approximately 1000 subjects for H pylori with the rapid CLO test during gastroscopy
Subjects who have a negative CLO test during endoscopy will be excluded from the study and will be managed accordingly by their physician
Subjects who are confirmed to have H pylori gastritis based on the CLO test will then be recruited into the study
Diagnosed H pylori positive patients n252 will be enrolled into four study groups
Group A Omeprazole 20mg bd Amoxicillin 1g bd Clarithromycin 500mg bd for 14 days
Group B Esomperazole 20mg bd Amoxicillin 1g bd Clarithromycin 500mg bd for 14 days
Group C Rabeprazole 20mg bd Amoxicillin 1g bd Clarithromycin 500mg bd for 14 days
Group D Vonoprazan 20mg bd Amoxicilllin 1g bd Clarithromycin 500mg bd for 7 days
Randomization codes will be generated by a computer program and all codes are placed into sealed opaque envelopes and kept by an independent biostatistician After obtaining informed consent the investigators would call the research assistant to open the envelope for the allocated regimen The allocation ratio for TTV and TTP groups is 11 with 126 patients in each group Within the TTP group the distribution of patients to each of the three PPIs OmeprazoleEsomeprazoleRabeprazole will be equal n42 each The compliance to treatment in terms of percentage of drugs taken will be assessed during clinic review
This will be a single centre prospective open-label randomized controlled study to i compare the eradication rates of H pylori by TTP regimen vs TTV regimen in a multi-racial Asian cohort ii evaluate the prevalence of antibiotic clarithromycin amoxicillin levofloxacin tetracycline resistance in H pylori-infected patients of both treatment groups and iii assess the safety of the TTV regimen The proposed study workflow is outlined in Figure 1 This study will be conducted in CGH in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with Good Clinical Practice applicable regulatory requirements
The demographic profile age gender ethnicity and clinical notes endoscopic findings antibiotic sensitivity testing results drug regimen prescribed extent of treatment compliance duration of therapy treatment outcomes ie eradication rate occurrence of adverse events etc of all patients enrolled into the study will be documented for data analysis
The following experiments will be conducted for the study
Efficacy assessment
The success of treatment ie eradication of H pylori is defined as a negative Carbon-13 urea breath test CUBT or negative histology test performed at week 6 CUBT or histology will be performed based on the clinical indication as determined by the attending physician All patients should be off antibiotics and PPI or Vonoprazan for at least 4 weeks prior to assessment of the success of treatment as per standard practice All routine laboratory tests will be carried out in Microbiology Lab Department of Laboratory Medicine CGH The technologists will be blinded to the treatment regimens
Antibiotic susceptibility testing
For patients with H pylori infection diagnosed during endoscopy from a positive rapid urease test kit the material from the test kit will be cultured for antibiotic sensitivity testing The antibiotic sensitivity testing results may be of value in guiding the choice of antibiotics for second line salvage treatment should first line treatment fails This has potential usage in the clinical management of patients
Gastric biopsy specimens collected from both greater gastric corpus and antrum during endoscopy will be inoculated into H pylori transport medium and transported with ice packs to the laboratory The biopsy samples will be ground with a tissue homogenizer cultured followed by susceptibility testing and determination of the minimum inhibitory concentration MIC Briefly culture will be performed with blood agar medium for Helicobacter with addition of 10 CO2 at 35C for 7 days The identity of H pylori is defined as Gram-negative bacillus with catalase test positive oxidase test positive and urease test positive The MIC of antibiotics clarithromycin amoxicillin levofloxacin tetracycline will be determined by E-test or agar plate dilution method in accordance with the guidelines established by the NCCLS Guidelines M100-S9 Mueller-Hinton agar 5 horse blood will be used with addition of 10 CO2 at 35C for 72 hours 21 The breakpoint for clarithromycin amoxicillin levofloxacin and tetracycline resistance is defined as 10mgL 05mgL 1mgL and 1mgL respectively according to the European Committee on Antimicrobial Susceptibility Testing EUCAST 2122 The laboratory personnel involved in the antibiotic sensitivity testing will be blinded to the study group allocation
Safety assessment
An adverse effect questionnaire AEQ will be completed by all patients during therapy The AEQ will contain a checklist to assess the occurrence of loose stools skin eruption abdominal bloating constipation nausea epigastric pain and dysgeusia
Detection of mutational hotspots for clarithromycin resistance
An in-house real-time PCR assay will be done on the DNA extracted from the cultured H pylori isolates to detect mutational hotspots for clarithromycin-resistance
Post-hoc CYP2C19 genotyping
Genomic DNA will be extracted from peripheral leukocytes of whole blood using standard desalting methods Genotyping for the two predominant single nucleotide polymorphisms CYP2C192 and CYP2C193 leading to intermediate heterozygous mutant and poor metabolizer phenotypes homozygous mutants will be performed using sequencing of restriction fragment length polymorphism methods
Subjects who have a negative CLO test during endoscopy will be excluded from the study and will be managed accordingly by their physician
Subjects who are confirmed to have H pylori gastritis based on the CLO test will then be recruited into the study
Diagnosed H pylori positive patients n252 will be enrolled into four study groups
Group A Omeprazole 20mg bd Amoxicillin 1g bd Clarithromycin 500mg bd for 14 days
Group B Esomperazole 20mg bd Amoxicillin 1g bd Clarithromycin 500mg bd for 14 days
Group C Rabeprazole 20mg bd Amoxicillin 1g bd Clarithromycin 500mg bd for 14 days
Group D Vonoprazan 20mg bd Amoxicilllin 1g bd Clarithromycin 500mg bd for 7 days
Randomization codes will be generated by a computer program and all codes are placed into sealed opaque envelopes and kept by an independent biostatistician After obtaining informed consent the investigators would call the research assistant to open the envelope for the allocated regimen The allocation ratio for TTV and TTP groups is 11 with 126 patients in each group Within the TTP group the distribution of patients to each of the three PPIs OmeprazoleEsomeprazoleRabeprazole will be equal n42 each The compliance to treatment in terms of percentage of drugs taken will be assessed during clinic review
This will be a single centre prospective open-label randomized controlled study to i compare the eradication rates of H pylori by TTP regimen vs TTV regimen in a multi-racial Asian cohort ii evaluate the prevalence of antibiotic clarithromycin amoxicillin levofloxacin tetracycline resistance in H pylori-infected patients of both treatment groups and iii assess the safety of the TTV regimen The proposed study workflow is outlined in Figure 1 This study will be conducted in CGH in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with Good Clinical Practice applicable regulatory requirements
The demographic profile age gender ethnicity and clinical notes endoscopic findings antibiotic sensitivity testing results drug regimen prescribed extent of treatment compliance duration of therapy treatment outcomes ie eradication rate occurrence of adverse events etc of all patients enrolled into the study will be documented for data analysis
The following experiments will be conducted for the study
Efficacy assessment
The success of treatment ie eradication of H pylori is defined as a negative Carbon-13 urea breath test CUBT or negative histology test performed at week 6 CUBT or histology will be performed based on the clinical indication as determined by the attending physician All patients should be off antibiotics and PPI or Vonoprazan for at least 4 weeks prior to assessment of the success of treatment as per standard practice All routine laboratory tests will be carried out in Microbiology Lab Department of Laboratory Medicine CGH The technologists will be blinded to the treatment regimens
Antibiotic susceptibility testing
For patients with H pylori infection diagnosed during endoscopy from a positive rapid urease test kit the material from the test kit will be cultured for antibiotic sensitivity testing The antibiotic sensitivity testing results may be of value in guiding the choice of antibiotics for second line salvage treatment should first line treatment fails This has potential usage in the clinical management of patients
Gastric biopsy specimens collected from both greater gastric corpus and antrum during endoscopy will be inoculated into H pylori transport medium and transported with ice packs to the laboratory The biopsy samples will be ground with a tissue homogenizer cultured followed by susceptibility testing and determination of the minimum inhibitory concentration MIC Briefly culture will be performed with blood agar medium for Helicobacter with addition of 10 CO2 at 35C for 7 days The identity of H pylori is defined as Gram-negative bacillus with catalase test positive oxidase test positive and urease test positive The MIC of antibiotics clarithromycin amoxicillin levofloxacin tetracycline will be determined by E-test or agar plate dilution method in accordance with the guidelines established by the NCCLS Guidelines M100-S9 Mueller-Hinton agar 5 horse blood will be used with addition of 10 CO2 at 35C for 72 hours 21 The breakpoint for clarithromycin amoxicillin levofloxacin and tetracycline resistance is defined as 10mgL 05mgL 1mgL and 1mgL respectively according to the European Committee on Antimicrobial Susceptibility Testing EUCAST 2122 The laboratory personnel involved in the antibiotic sensitivity testing will be blinded to the study group allocation
Safety assessment
An adverse effect questionnaire AEQ will be completed by all patients during therapy The AEQ will contain a checklist to assess the occurrence of loose stools skin eruption abdominal bloating constipation nausea epigastric pain and dysgeusia
Detection of mutational hotspots for clarithromycin resistance
An in-house real-time PCR assay will be done on the DNA extracted from the cultured H pylori isolates to detect mutational hotspots for clarithromycin-resistance
Post-hoc CYP2C19 genotyping
Genomic DNA will be extracted from peripheral leukocytes of whole blood using standard desalting methods Genotyping for the two predominant single nucleotide polymorphisms CYP2C192 and CYP2C193 leading to intermediate heterozygous mutant and poor metabolizer phenotypes homozygous mutants will be performed using sequencing of restriction fragment length polymorphism methods
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?:
None
Is an FDA AA801 Violation?:
None