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Trial registered on ANZCTR


Registration number
ACTRN12625000169448
Ethics application status
Approved
Date submitted
19/01/2025
Date registered
13/02/2025
Date last updated
13/02/2025
Date data sharing statement initially provided
13/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment and Resistance Of Helicobacter Pylori in Waitemata, Auckland
Scientific title
Treatment and Resistance Of Helicobacter Pylori in Symptomatic Patients in Waitemata, Auckland
Secondary ID [1] 313758 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Helicobacter pylori infection 336360 0
Condition category
Condition code
Infection 332894 332894 0 0
Studies of infection and infectious agents
Oral and Gastrointestinal 332895 332895 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A single centre prospective study of consecutive patients attending for gastroscopy who have biopsies to assess for Helicobacter Pylori (H. pylori) (clinician discretion) .

Questionnaire provided: 15 questions assessing demographic data and socioeconomic data points which takes 5-10 minutes to fill. This is completed before the biopsy below.

Gastroscopy performed. 2x gastric biopsies obtained from the antrum and body for immediate urease testing. The urease test, also known as CLO testing (campylobacter-like organism test) is a rapid, sensitive and cost-effective test. This is held at ambient air temperature and read within 60 minutes for positivity.

4 further biopsies (2 from antrum, 2 from body) obtained for culture and placed into 1 ml of brain-heart infusion (BHI) broth, labelled with patient information and refrigerated. This is sent to microbiology department at Middlemore Hospital within 24 hours if the Urease test is positive, otherwise it is discarded.

Positive CLO samples are sent to the Malaghan Institute of Medical Research, Wellington, for polymerase chain reaction (PCR) testing. Phenotypic resistance to each antibiotic will be determined by detecting specific mutations which typically alter the uptake or efflux of the antibiotic. DNA extraction will be performed using a commercially available DNA extraction kits. The DNA will be stored at -80°C until testing is performed. The presence of H. pylori DNA will be confirmed using PCR. Molecular testing for mutations conferring antimicrobial resistance will be tested using droplet digital PCR.

Duration of observation for each participant will be from time of enrolment for 12 months
Intervention code [1] 330338 0
Not applicable
Comparator / control treatment
Traditional culture based method: Culture samples will be macerated using a sterile scalpel blade and inoculated onto two Brucella agar plates of 5% sheep blood (Fort Richard Laboratories). The inoculated plates are then incubated at 37°C in microaerophilic conditions using a CampyGen generator (Oxoid) and examined for typical colonies for up to 10 days.

Susceptibility testing will be performed on any identified curved gram negative bacilli that was both oxidase and urease positive. Minimum inhibitory concentrations (MIC) of amoxicillin, clarithromycin, tetracycline, metronidazole and moxifloxacin will be performed by E-test. A suspension of organism will be prepared in saline to a two MacFarland standard density. This suspension is then used to inoculate Mueller Hinton 5% sheep blood agar plates (Fort Richard Laboratories). One E-test is applied per plate and incubated at 37°C for 72 hours in microaerophilic conditions before reading the MIC
Control group
Active

Outcomes
Primary outcome [1] 340421 0
Amoxicillin resistance
Timepoint [1] 340421 0
At diagnosis
Primary outcome [2] 340545 0
clarithromycin resistance
Timepoint [2] 340545 0
At diagnosis
Primary outcome [3] 340546 0
Metronidazole resistance rates.
Timepoint [3] 340546 0
At diagnosis
Secondary outcome [1] 443992 0
Clarithromycin Resistance
Timepoint [1] 443992 0
At diagnosis
Secondary outcome [2] 443993 0
Success of first line empirical therapy (overall successful H.pylori eradication)
Timepoint [2] 443993 0
All patients checked for successful eradication with H. pylori faecal antigen test performed at least 4 weeks after last medication dose, and 2 weeks off proton pump inhibitor (PPI) therapy.
Secondary outcome [3] 443994 0
Susceptibility/resistance testing modalities as a predictor for treatment success
Timepoint [3] 443994 0
At diagnosis and at least 4 weeks after treatment (with stool test)
Secondary outcome [4] 443996 0
Assessment reinfection rates at 1 year
Timepoint [4] 443996 0
1 year after confirmed successful treatment
Secondary outcome [5] 443998 0
Rates of virulence factors, i.e. CagA
Timepoint [5] 443998 0
At time of diagnosis
Secondary outcome [6] 444414 0
Rates of virulence factor: Vac A
Timepoint [6] 444414 0
At diagnosis

Eligibility
Key inclusion criteria
Attendance for a gastroscopy where there is a clinical suspicion H.pylori may be contributory to the presentation and biopsies are likely to be taken to test for H.pylori infection.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Contraindication to biopsy
• Unable to provide consent
• Previous H.pylori eradication regimen prescribed

Study design
Purpose
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Power calculations for determining sample size requirements were performed using the designated primary objective of the study to evaluate the discriminative ability of antimicrobial resistance testing with PCR to detect the results of culture-based antibiotic susceptibility testing. Diagnostic accuracy power calculations (NCSS PASS 2002, Utah, USA) showed that a minimum of 97 participants were required with an estimated cohort clarithromycin resistance proportion of 16%, prevalence of 40%, anticipated sensitivity of 90%, absolute precision of 15%, and a two-sided statistical significance level of 5% (a=0.05).

Statistical analysis will be performed using R version 4.0.2 (R Foundation, Vienna, Austria). The discriminative ability of antimicrobial resistance testing with PCR to detect the results of culture-based antibiotic susceptibility testing will be determined by the area under the receiver operating characteristic curve (C-statistic), and compared using the independent Hanley test, and diagnostic sensitivity and specificity values calculated. Inter-group comparisons of normally distributed continuous variables were conducted using the independent samples t test, following confirmation with Shapiro-Wilk normality testing (p>0.05). Non-normally distributed continuous data were compared using the Mann-Whitney U test, and categorical data analysed using the chi-squared and Fisher’s exact tests. Preliminary univariate logistic regression will be used to identify potential predictors of antimicrobial resistance. Multivariable logistic regression for predictors of therapy resistance will then be conducted, incorporating variables with a univariate association threshold of p<0.15. The number of variables used in the multivariate regression analysis will be limited to the number of resistant cases divided by 10, to avoid overfitting. False discovery rate adjustment of p-values will be applied for multiple comparisons, and all tests will be two-tailed and p<0.05.

An additional review of patient factors who are biopsied for H. pylori but are negative, compared to those who are biopsied and are positive will be undertaken.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/02/2025
Actual
Date of last participant enrolment
Anticipated
3/02/2027
Actual
Date of last data collection
Anticipated
3/02/2028
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment outside Australia
Country [1] 26833 0
New Zealand
State/province [1] 26833 0
Auckland

Funding & Sponsors
Funding source category [1] 318212 0
Government body
Name [1] 318212 0
Te Whatu Ora - Waitemata - 2024 Waitemata District Contestable Research Grant
Country [1] 318212 0
New Zealand
Primary sponsor type
Government body
Name
Te Whatu Ora - Waitemata
Address
Country
New Zealand
Secondary sponsor category [1] 320601 0
None
Name [1] 320601 0
Address [1] 320601 0
Country [1] 320601 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316861 0
Northern A Health and Disability Ethics Committee 
Ethics committee address [1] 316861 0
https://ethics.health.govt.nz/about/northern-a-health-and-disability-ethics-committee/
Ethics committee country [1] 316861 0
New Zealand
Date submitted for ethics approval [1] 316861 0
11/08/2024
Approval date [1] 316861 0
22/08/2024
Ethics approval number [1] 316861 0
2024 EXP 21063

Summary
Brief summary
We are aiming to review the resistance and treatment success, and factors associated with this, of a common bacteria, Helicobacter pylori in patients coming for investigation with gastroscopy of abdominal complaints. We hope to be able to use this data to update treatment guidelines.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139234 0
Dr Cameron Schauer
Address 139234 0
C/O Gastroenterology Department, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0620
Country 139234 0
New Zealand
Phone 139234 0
+64210368637
Fax 139234 0
Email 139234 0
[email protected]
Contact person for public queries
Name 139235 0
Cameron Schauer
Address 139235 0
C/O Gastroenterology Department, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0620
Country 139235 0
New Zealand
Phone 139235 0
+64210368637
Fax 139235 0
Email 139235 0
[email protected]
Contact person for scientific queries
Name 139236 0
Cameron Schauer
Address 139236 0
C/O Gastroenterology Department, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0620
Country 139236 0
New Zealand
Phone 139236 0
+64210368637
Fax 139236 0
Email 139236 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The resistance profiles and patient factors.
When will data be available (start and end dates)?
Available for 5 years after publication
Available to whom?
De-identified data may be shared with with other researchers on specific request
Available for what types of analyses?
Statistical analyses / meta-analyses
How or where can data be obtained?
Via contact with the research team and lead investigator - myself ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.