Helicobacter Pylori Infection Clinical Trial
Official title:
Sequential Helicobacter Pylori Eradication Therapy in Myanmar; a Randomized Clinical Trial of Efficacy and Tolerability
This study aims to:
1. Determine the prevalence of Helicobacter infection in Myanmar (this would be the largest
ever series in the country)
2. Determine the clinical and epidemiological associations of Helicobacter infection in
Myanmar
3. Determine the utility of stool antigen testing to diagnose the infection and confirm
eradication
4. Compare the relative efficacies of concomitant and sequential therapy
5. Determine the relative efficacies of first, second and third line therapies in Myanmar
in 2018
There are very few published studies to examine the prevalence of Helicobacter infection in
Myanmar. Two previous studies (both < 400 participants) suggested that the prevalence was
approximately 50% (Myint WJG 2015, Aye MMJ 2015).
The high prevalence of H.pylori is important because gastric adenocarcinoma is the fourth
most common cancer in the country (WHO 2014). Gastric cancer has an almost uniformly dismal
5-year survival rates in this resource-limited country and is estimated to kill almost 5000
patients per year in Myanmar (WHO 2014).
In addition, anecdotally there is a significant associated burden of peptic ulcer disease in
the country, although there are few published data to examine the issue.
Strategies to diagnose and eradicate H.pylori must be considered in the context that the
annual per capita health budget is USD103 (World Bank 2016).
Therapeutic regimens must also consider the issue of antimicrobial resistance, which varies
from country to country. There are very few data from Myanmar to guide us and those that are
available vary enormously.
In vitro antibiotic resistance by agent
Amoxycillin 0%, 8%, 7%
Metronidazole 33%, 54%,100%
Clarithromycin 0%, 13%, 50%
Levofloxacin 6%, NR, 3%
Tetracycline 0%, NR, NR
Ciprofloxacin 6%, NR NR
Studies: Mahachai 2012, Aye 2005, Aye 2014
However, it is also known that in vitro resistance does not necessarily translate into in
vivo failure. Furthermore in a resource poor setting like Myanmar, a strategy of
susceptibility guided treatment is not feasible. Indeed, this is not likely to be
cost-effective in even wealthy countries (ACG guidelines 2017 and Maastricht consensus
guidelines 2017).
The current first line therapy for H.pylori in Myanmar is 10-14 days of concomitant bd PPI +
bd Clarithromycin + bd Amoxycillin + bd metronidazole. This regimen contains up to 126 pills
(14 days) and costs up to USD16 (14 days). It is likely that 14 days of 4 drug therapy will
generate issues with side effects and adherence, although again this has not been examined
locally.
Alternatively, a 10-day sequential regimen of 5 days of bd PPI + Amoxycillin, then 5 days of
bd PPI + Clarithromycin and Tinidazole reduces the pill load to 50 pills and the total drug
cost to USD6. This regimen has been shown to be highly effective in Slovenia (94.2%),
Portugal (90%), Belgium (90%), Israel (95.9%), Thailand (94%), Taiwan (91.9%), Singapore
(90.3%), and the United Arab Emirates (88.6%) (Review, De Francesco 2017).
A sequential regimen has been shown to have less satisfactory success rates in Greece ,
Spain, Ireland, Turkey, Iran, Korea, China, and Puerto Rico (although in many of these
studies, metronidazole was used instead of tinidazole (Review, De Francesco 2017)).
The current second-line regimen in Myanmar is 10-14 days of bd PPI + Levofloxacin +
Amoxycillin (pill load 80 pills for 10 days, total cost USD3). In this era of evolving drug
resistance, we may not want to use quinolones as first line therapy however.
The current third line therapy is Bismuth based quadruple therapy (BQT). This regimen is
comprised of Bismuth + PPI + Tetracycline + Tinidazole (pill load 120 pills, total cost
USD50)
The proposed study aims to demonstrate that a 10-day course of sequential therapy is not
inferior to 14 days of 4 drug concomitant therapy. Assuming a cure rate of 80% for
Concomitant 4 drug therapy, and an inferiority bound of 10%, the sample size is 626 (313
patients in each arm). To identify 626 patients, we will need to screen approximately 1250
patients. In this resource-poor setting, diagnosis will be established using monoclonal stool
antigen testing (SAT BioMerieux BioNexia). Patients who test positive with SAT will be
randomised 1:1 in an open label study to either a 10-day course of sequential therapy or the
current first line regimen of concomitant 4 drug therapy. Four weeks after completing
therapy, eradication will be confirmed with repeat SAT.
Those patients failing the first line therapy would then receive second line levofloxacin and
then tested to confirm eradication. This would determine the efficacy of the country's
current second line therapy.
Finally, patients failing first and second line therapy would receive the more involved and
expensive third line therapy. Once again, this would determine the efficacy of third line
therapy.
To ensure all participants had their H.pylori infection eradicated, those failing three lines
of therapy would be offered endoscopy and culture directed therapy.
The performance of the stool antigen test is affected by the PPI therapy, so the study can't
easily enrol patients presenting with acute symptoms who will frequently have already been
taking PPI therapy (higher rate of false negatives). Therefore, the study will enrol
outpatients about to commence aspirin, NSAIDs or anticoagulants (in whom the risk of GI
bleeding is higher) or patients with a personal history of peptic ulcer disease or family
history of gastric cancer. These are all indications for H.pylori testing (ACG guidelines
2017 and Maastricht consensus guidelines 2017).
Outputs
1. The prevalence of H.pylori in Yangon, Myanmar
2. Clinical and demographic associations of H.pylori infection in Myanmar
3. Efficacy of
1. Current first line therapy: 14 days of concomitant PPI + amoxy + clari + metro
2. Alternative: 10 days of sequential PPI + amoxy + clari + Tinidazole
3. Current second line therapy: 14 days of PPI + Levo + Amoxy
4. Current third line therapy: 14 days of Bismuth + PPI + tetracycline + metro (BQT)
4. Acceptability - to patients and staff - of stool antigen testing for H.pylori screening
and for confirming eradication.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05061732 -
Helicobacter Pylori Eradication and Follow-up
|
Phase 4 | |
Completed |
NCT03779074 -
Comparing the Efficacy of Hybrid, High-dose Dual and Bismuth Quadruple Therapies
|
Phase 3 | |
Completed |
NCT06076681 -
A Study to Evaluate Preliminary Helicobacter Pylori Eradication After Multiple Doses of TNP-2198 Capsules Combined With Rabeprazole Sodium Enteric-coated Tablets, or Rabeprazole Sodium Enteric-coated Tablets and Amoxicillin Capsules
|
Phase 1/Phase 2 | |
Recruiting |
NCT05329636 -
Auto Fecal Microbial Transplant Post Helicobacter Pylori Antibiotic Therapy
|
Phase 1/Phase 2 | |
Recruiting |
NCT05065138 -
Comparison of Helicobacter Pylori Eradication Effect Before and After Training of Gastroenterologists
|
N/A | |
Completed |
NCT05049902 -
Bismuth-containing Quadruple Therapy for Helicobacter Pylori Eradication
|
Phase 4 | |
Not yet recruiting |
NCT06200779 -
Tailored vs. Empirical Helicobacter Pylori Infection Treatment
|
Phase 4 | |
Not yet recruiting |
NCT06037122 -
Efficacy of Low-dose Vonoprazan for Helicobacter Pylori Eradication
|
||
Completed |
NCT04617613 -
Comparing Different Regimens for Eradication of Helicobacter Pylori in Kuwait
|
Phase 4 | |
Withdrawn |
NCT02552641 -
Food Effect on the Eradication Rate of H. Pylori With Triple Therapy With Esomeprazole
|
Phase 4 | |
Completed |
NCT02873247 -
Standardize Communication With General Practitioner & Patient for Improved Eradication of Helicobacter Pylori
|
||
Completed |
NCT02557932 -
Comparison of 7-day PPI-based Standard Triple Therapy and 10-day Bismuth Quadruple Therapy for H. Pylori Eradication
|
Phase 3 | |
Recruiting |
NCT02249546 -
Efficacy of Acetylcysteine-containing Triple Therapy in the First Line of Helicobacter Pylori Infection
|
Phase 4 | |
Completed |
NCT01933659 -
Anti-H. Pylori Effect of Deep See Water
|
Phase 3 | |
Unknown status |
NCT01464060 -
14-day Quadruple Hybrid vs. Concomitant Therapies for Helicobacter Pylori Eradication
|
Phase 4 | |
Completed |
NCT00841490 -
Oral H. Pylori Prevalence in Intellectually & Developmentally Disabled Adults
|
N/A | |
Recruiting |
NCT05728424 -
One vs Two Weeks Treatment for H.Pylori Eradication A RANDOMIZED NON-INFERIORITY PLACEBO CONTROLLED TRIAL
|
Phase 3 | |
Recruiting |
NCT05549115 -
Susceptibility-Guided Sequential Therapy for Helicobacter Pylori Infection
|
N/A | |
Recruiting |
NCT05997433 -
Efficacy of 7-day Versus 14-day Bismuth Quadruple Therapy for the Eradication of Helicobacter Pylori(SHARE2302)
|
N/A | |
Completed |
NCT04708405 -
The Relationship Between Helicobacter Pylori Infection and Inflammatory Bowel Diseases: A Real-life Observation
|