Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06315478 |
| Other study ID # |
Hybrid regimen for H.pylori |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2021 |
| Est. completion date |
November 1, 2021 |
Study information
| Verified date |
March 2024 |
| Source |
Helwan University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Our study aimed to investigate the efficacy and safety of hybrid regimen as a first line
therapy for H. pylori eradication compared to triple and quadruple regimens in attempt to
overcome antibiotic resistance
Description:
Helicobacter pylori (H. pylori) is a globally prevalent pathogen which infects about over 50%
of population. However, not all cases have clinical symptoms, H. pylori are described as gram
negative bacteria which causes ulcers in the lining of stomach or the upper part of small
intestine. For some patients, a progressive infection can cause gastric cancer which is the
second widespread cancer worldwide (1).
While this pathogen in Egypt is a public health issue, the propagation of H. pylori infection
is approximately 80% (2), study results concluded that H. pylori infection in upper Egypt was
higher than in urban areas (3).
Transmission modes of H. pylori are very controversial, the reservoir of H. pylori is the
human stomach. The main method of acquisition in both developing and developed countries by
fecal oral route, whereas the other route of transmission in developed countries is the
gastro-oral route mainly water borne prevalence, overcrowding of the family of large number
members, institutionalized children are predisposing for acquiring the infection. (4:6), and
occupational risk factor for health members, in particular those working in gastrointestinal
units (7). Over spread of the infection in upper Egypt could be due to the hygiene level,
socioeconomic conditions, life style, and absence of sources of pure water supply in rural
areas (3).
H. pylori has been classified as one of the 12 bacterial species need high priority future
strategies for new antibiotic development by the World Health Organization (WHO), management
of H. pylori is widely debatable due to high antibiotics resistance prevalence after
exclusion of inadequate gastric suppression by proton pump inhibitor and poor adherence to
the therapy. Furthermore, the efficacy of many regimens has declined due to increased
antibiotic resistance making H. pylori eradication challenging, H. pylori treatment has been
complicated and has required 10 and 14 days of multiple daily doses of three or four
different medicines. (8:13).
There is no worldwide accepted regimen for the eradication of H. pylori infection. Standard
triple therapy (STT) with proton pump inhibitors (PPI) in standard dose, clarithromycin (500
mg), and amoxicillin (1 g) twice daily for 14 days is the standard triple first line regimen
in the published international guidelines of the European Helicobacter and Microbiota Study
Group in areas of low clarithromycin resistance (14).
A randomized controlled trial in Japan showed that clarithromycin resistance is a growing
problem found metronidazole to be superior to clarithromycin as a 7-day first-line triple
regimen (15).
In regions with low dual clarithromycin and metronidazole resistance (<15%), either a bismuth
quadruple therapy (BQT) (PPI, bismuth salt, tetracycline, and metronidazole) or non-bismuth
concomitant quadruple therapy (PPI, amoxicillin, clarithromycin, and metronidazole) is
recommended (14,16), In areas of high dual clarithromycin and metronidazole resistance
(>15%), bismuth quadruple therapy is the recommended regimen. However, bismuth isn't
available in all regions and not preferred due to complexity and the high pill burden (14
pills per day). Therefore, levofloxacin, rifabutin or high dose dual (amoxicillin and PPI)
therapies have been suggested (14,17).
A levofloxacin triple therapy is recommended as second-line treatment in case of first line
therapy failure; However, clarithromycin-based triple therapy or bismuth quadruple therapy
are alternative second-line options if not used as first line regimen and clarithromycin
resistance is known to be low.
Third-line and subsequent treatment strategies should be guided by antimicrobial
susceptibility testing, treatment durations of 14 days and the use of newer generation PPIs
are recommended in all H. pylori regimens, unless local evidence suggests that 10 days
therapy is efficient (14,18,19). In Egypt, the first and second line H. pylori regimens as
the international guidelines are used to eradicate H.pylori. However, these recommendations
should be reviewed, due to increased resistance rate and progressive decline in eradication
therapy efficacy. (20).
Expert groups in USA, Canada, and Europe have issued treatment guidelines for the management
of H. pylori infection to overcome the global challenge of antibiotic resistance (13).
Treatment of H. pylori is still widely empiric due to antibiotic resistance, which could be
prevented through culture guided therapy that associated with higher eradication rates
(21,22).
Some experts such as the Maastricht guidelines recommend clarithromycin susceptibility
testing before prescribing clarithromycin triple regimen or after second line regimen
failure, its preferable to have this test in an earlier phase than waiting for two treatment
failures mostly due to increased levofloxacin resistance, a component of many second line
therapies (14,23,24).
Antibiotic susceptibility testing can be done by culture or molecular methods, both of which
require gastric biopsies. However. This test is less cost-effective to be adopted widespread
(23). The scarcity of such data in USA was an obstacle to make strong evidence-based
treatment recommendations in the 2017 ACG guideline on H. pylori treatment (19).
In USA, only two publications in the previous 20 years including fewer than 500 strains of H.
pylori have revealed resistance features (13,25,26) A recent study compared the efficacy of
first-line H.pylori eradication therapies including STT, BQT, sequential therapy (ST)
consisting of a PPI and amoxicillin for 5-7 days followed by a PPI, clarithromycin, and a
metronidazole for 5-7 days, and HT. Results revealed that hybrid regimen had the best
H.pylori eradication rates (27).
Another study compared the efficacy of different regimens for eradication of H. pylori had
shown that A 14-day hybrid therapy has attracted global attention as this regimen proved to
be safe, well tolerated and effective in high antibiotic resistance settings (28,29).
A current hybrid therapy (HT) (PPI and amoxicillin for 14 days followed by clarithromycin and
a nitroimidazole for 7 days) is a promising first-line strategy for H. pylori eradication due
to the rising prevalence of antibiotic resistance globally (30).
To the best of our knowledge there is lacking information about hybrid regimen efficacy in
eradication of H.pylori infection in Egyptian patients, our study aimed to investigate the
efficacy and safety of hybrid regimen as a first line therapy for H. pylori eradication
compared to triple and quadruple regimens in attempt to overcome antibiotic resistance.
