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Published in final edited form as:
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Helicobacter. 2011 April ; 16(2): 139–145. doi:10.1111/j.1523-5378.2011.00828.x.

Modified sequential H. pylori therapy: PPI and amoxicillin for 14

days with clarithromycin and metronidazole added as a
quadruple (hybrid) therapy for the final 7 days
Ping-I Hsu1, Deng-Chyang Wu2, Jeng-Yih Wu2,3, and David Y Graham4
1Divisionof Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General
Hospital and National Yang-Ming University, Kaohsiung, Taiwan
2Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University
Hospital, Kaohsiung, Taiwan
3Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
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4Department of Medicine, Veterans Affairs Medical Center, and Baylor College of Medicine,
Houston, Texas, USA

Abstract
Background—Ten day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin
followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori
eradication rates of 90 to 94% (Grade B success).

Aims—We tested whether prolonging treatment and continuing amoxicillin throughout the 14-
day treatment period would produce a ≥95% result.

Methods—This was a multi-center pilot study in which H pylori infected patients received a 14-
day sequential-concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by
esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H pylori status was
examined 8 weeks after therapy. Success was defined as achieving ≥95% eradication by per-
protocol analysis.
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Results—117 subjects received hybrid therapy. The eradication rate was 99.1% (95% CI,
97.3%–100.0%) by per-protocol analysis and 97.4% by intention-to-treat analysis (95% CI, 94.5–
100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%.

Conclusions—14-day hybrid sequential-concomitant therapy achieved greater than 95% H.

pylori eradication (Grade A result). Further studies are needed (i) in regions with different patterns

Requests for reprints to: Dr. Ping-I Hsu, Division of Gastroenterology, Department of Internal Medicine, Kaoshiung Veterans General
Hospital, 386 Ta Chung 1st Road, Kaohsiung 813, Taiwan, R.O.C.; Tel: +886-7-3462074; Fax: +886-7-3468237;
williamhsup@yahoo.com.tw.
Contributions of authors: Dr David Y Graham: designed the study, participated in data analysis and revised the manuscript; Dr Ping-I
Hsu: participated in study design, collected the cases, performed endoscopy and urease test, analyzed the data and wrote the
manuscript; Dr Deng-Chyang Wu: participated in study design, collected the cases and performed antibiotic susceptibility test; Dr
Jeng-Yih Wu: collected the cases.
Conflict of interest
Dr JY Wu discloses no conflicts
 Hsu et al. Page 2

and frequencies of resistance to confirm these findings and (ii) to examine whether Grade A
success is maintained with hybrid therapy shorter than 14 days.
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Keywords
Helicobacter pylori; sequential therapy; clinical trial; amoxicillin; clarithromycin; metronidazole

Introduction
Until recently triple regimen with a proton pump inhibitor (PPI) plus clarithromycin and
amoxicillin or metronidazole administered for 7 to 14 days was often regarded as the gold
standard for H pylori eradication [1,2]. It has become recognized that treatment success with
this regimen has generally declined to unacceptable levels (i.e., 80% or less) [ 3] and that the
fall in efficacy is primarily related to an increase in the prevalence of clarithromycin-
resistance [4,5].

The decline in treatment success with triple therapy resulted in the introduction of new
regimens such as a 10-day sequential regimen consisting of a dual therapy (PPI and
amoxicillin for 5 days), followed by triple therapy with a PPI, clarithromycin and tinidazole
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(or metronidazole) triple therapy for 5 days [6,7] The mean H pylori cure rate of the new
therapy has been reported to be 91.3% by intention-to-treat (ITT) analysis [6] and recent
studies with antimicrobial susceptibility testing have confirmed that the superiority of
sequential therapy over standard triple therapy is primarily due to an improved outcome with
clarithromycin-resistant strains [6,7] However, sequential therapy has not reliably achieved
95% or greater treatment success or Grade A success based on grading treatment success as
ordered categories (by PP analysis) of ≥95% = A, 90–94% = B, 86–89% = C and ≤ 85% =
F) [8–10]. In contrast, treatment success of common bacterial infections is not typically
based on a comparison to another regimen but rather acceptable or unacceptableness is
based on absolute outcome. [11,12].

The factors that affect outcome of sequential therapy such as dose, duration etc [12] were
chosen empirically and the regimen has not yet been optimized. It has been suggested that
sequential might be improved by increasing the duration of therapy (e.g., to more than 10
days) [9,10,13]. Here we used the recently describe three stage approach to identifying a
regimen with high treatment success [14]. These steps include: 1) pilot studies to identify
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tentative highly successful regimens, 2) further pilot studies to simplify and refine the
regimen while maintaining the efficacy of 95% or greater, and 3) large scale multicenter
trials to confirm that the optimal therapy is successful in different regions with different
patterns of disease, and antimicrobial susceptibility.

Concomitant therapy is another regimen proven successful in the presence of clarithromycin

resistance and superior to triple therapy [15]. Concomitant therapy is a 4-drug non-bismuth
containing regimen containing the same drugs as does sequential therapy but they are all
given for the entire duration of therapy instead of sequentially. A head-to-head non-
inferiority trial of sequential and concomitant therapy showed they were equivalent,
however, in that trial neither achieved 95% treatment success [13]. It has previously been
suggested that sequential might be improved by continuing the amoxicillin throughout the

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entire treatment period which would produce a sequential-concomitant quadruple therapy

(hybrid therapy) [9,10,13]. In this study, we report the results the initial pilot study to
investigate whether increasing the duration of sequential therapy to 14-days and continuing
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the amoxicillin throughout the 14-day treatment period resulted in ≥95% treatment success.
The second pilot study tested whether increasing the duration of sequential therapy to 14
days (7+7) would produce treatment success to 95% or greater. The results can be found in
the companion paper [16].

Methods
Setting and Participants
The study was designed as two concomitantly conducted but separate pilot studies [14,17].
Patients were randomized into the two pilot study in order to eliminate selection bias. The
details of that study are found in the companion paper [16]. Patients who visited the
gastroenterology clinics of the Kaohsiung Veterans General Hospital, Kaohsiung Medical
University, and Kaosiung Municipal Hsiao-Kang Hospital between August 2008 and
January 2010 for dyspeptic symptoms were surveyed for H pylori infection. Those with H
pylori infection were recruited. Pre-enrollment procedures included biopsy of gastric
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mucosa where the presence of H pylori was assessed by rapid urease test and histological
examination. Active H pylori infection was defined as positive results of both rapid urease
test and histology. Blood samples were taken for routine laboratory tests including complete
blood count, renal function and liver biochemical tests to ascertain that there were no
abnormal tests that would preclude entry into the trial.

Exclusion criteria included (a) previous attempted H pylori-eradication therapy, (b)

ingestion of antibiotics, bismuth, or PPIs within the prior 4 weeks, (c) patients with allergic
history to the medications used, (d) patients with previous gastric surgery, (e) the
coexistence of serious concomitant illness (for example, decompensated liver cirrhosis,
uremia), (f) pregnancy or lactation, and (g) presence of serous medical condition(s)
precluding participation or endoscopy with biopsy.

Intervention
Eligible patients received a sequential-concomitant hybrid therapy (hybrid therapy
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consisting of esomeprazole 40 mg and amoxicillin 1 g twice daily for 7 days followed by

esomeprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg
twice daily for 7 days). All drugs were taken one hour before breakfast and dinner. Patients
were given a written instruction on how to take the medications correctly.

A trained interviewer used a standard questionnaire to obtain demographic data and medical
history of the patients. Patients were asked to return two weeks after the start of drug
administration to assess drug compliance and adverse events. Drug compliance was assessed
via pill counts. Compliance was defined as good defined as taking more than 90% of the
total medication or poor (i.e., taking less) by counting unused medication. As is the standard
practice locally, patients with peptic ulcers at the initial endoscopy received an additional
three weeks of monotherapy with esomeprazole 40 mg orally once daily whereas patients

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with H. pylori gastritis without peptic ulcer received three-weeks of antacid (aluminum
hydroxide 334 mg, Lederscon®, Taiwan, q.d.s.) following eradication therapy.
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Eradication efficacy was assessed by a follow-up endoscopy with rapid urease test and
histological examination eight weeks after the end of anti-H. pylori therapy. If patients
declined follow-up endoscopy, 13C-urea breath tests were conducted to assess H. pylori
status. Eradication was defined as either negative results of both rapid urease test and
histology, or a negative result of the urea breath test.

All participants gave written informed consent. The Medical Committee of the Kaohsiung
Veterans General Hospital approved the trial (VGHKS97-CT6-08). The study was registered
on ClinialTrials.gov; registrations # NCT01085786.

Questionnaires
A complete medical history and demographic data were obtained from each patient,
including age, sex, medical history, history of smoking, and alcohol, coffee and tea
consumption. Adverse events were prospectively evaluated. The adverse events were
assessed according to a 4-point scale system: none; mild (discomfort annoying but not
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interfering with daily life); moderate (discomfort sufficient to interfere with daily life); and
severe (discomfort resulting in discontinuation of eradication therapy) [18]. All participants
gave written informed consent. The Medical Committee of the Kaohsiung Veterans General
Hospital approved the trial (VGHKS97-CT6-08). The study was registered on
ClinialTrials.gov; registrations # NCT01085786.

Rapid urease test

The rapid urease test was performed according to our previous studies [19]. A biopsy
specimen taken from the antrum was placed immediately in 1 mL of a 10% solution of urea
in deionized water (pH 6.8) to which two drops of 1% phenol red solution was added and
incubated at 37°C for up to 24 hours. If the yellowish color around the area of inserted
specimen changed to bright pink within the 24-hour limit, the urease test was considered
positive. In our laboratory, the sensitivity and specificity of rapid urease test were 96% and
91% respectively [19].

Histological examination
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Gastric specimens were taken one specimen from the lesser curvature site of the antrum and
another from the lesser curvature site of the corpus for histological examination, fixed in
10% 10% buffered formalin, embedded in paraffin, and sectioned. The sections, 4-μm thick,
were stained with a haematoxylin and eosin stain and a modified Giemsa stain to observe the
presence of curved rod shape bacteria on the mucosal surface. Biopsy specimens were
assessed by histopathologists, blinded to patient status and the results of other laboratory
tests.

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Urea breath test

The urea breath test was performed according to our previous studies [20]. The cutoff value
was set at 4.8‰ of δ13CO2. The staff who were blind to the H. pylori status performed the
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tests.

Culture and antimicrobial resistance

Culture of H pylori was performed in the patients recruited from the Kaohsiung Veterans
General Hospital and the Kaohsiung Medical University as in both sites culture facilities
were available. One antral gastric biopsy specimen was obtained for isolation of H pylori,
using previously described culture methods [21]. The organisms were identified as H pylori
by Gram staining, colony morphology, and positive oxidase, catalase, and urease reactions.

The antibiotic susceptibility was tested by E test (AB Biodisk, Solna, Sweden). H pylori
subculturing was done by rubbing the specimens on the surface of a Campy-BAP agar plate
(Brucella agar; Difco, Sparks, Maryland) + IsoVitalex (Gibco, Grand Island, New York) +
10% whole sheep blood) followed by incubation at 37°C under microaerobic conditions (5%
O2, 10% CO2, and 85% N2) for 4–5 days. H pylori strains were tested for clarithromycin,
amoxicillin, and metronidazole susceptibility using the E-test (AB Biodisk, Solna, Sweden).
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H pylori strains with a minimal inhibitory concentration value >1 μg/mL >0.5 μg/mL, and
>8 μg/mL, were considered to be resistant to clarithromycin, amoxicillin, and metronidazole,
respectively [22].

Statistical analysis
The study was designed as a pilot study based on the three stage approach to identify a new
effective therapy [14, 17]. The requirement for treatment success of ≥95% was based on the
concept that H pylori is an infectious disease and the results should be similar to other
infectious diseases [3,11,12,14]. With infectious diseases such as H. pylori infection there is
essentially no placebo effect (i.e., treatment success with placebo is zero) and results less
than 99–100% can almost always be explained in terms of resistance, or failure to use the
dosages or duration of therapy. As such there is no need for, or advantage to use of, a
comparator regimen as the treatment results can be judged based on achieving an eradication
rate equal to or greater than a prespecified outcome (e.g., 100% success) [12]. Based on the
results of our prior study, [13] we expected the eradication rate when used as an empiric
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therapy to be greater than 90% (i.e., to fall between 93 and 99%).

Success was prespecified as a cure rate ≥95% (i.e., Grade A) by per-protocol (PP) analysis
and failure as treatment success lower than 95% [14]. The primary analysis was PP. Of note,
intention-to-treat (ITT) analyses have been described as most suitable for pragmatic trials of
effectiveness rather than for explanatory investigations of efficacy [23].

Sample sizes for pilot studies of new therapies are generally somewhat arbitrary (i.e., there
is no null hypothesis and the goal is usually to obtain an estimate of the effectiveness so as
to design new studies more effectively). Here, success was defined as being able to eradicate
at least 95% of infections. The choice of a sample size has both practical issues (e.g., cost,
availability of subjects) and the level of confidence in the results one desires. The 95%

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confidence interval (CI) decreases as sample size increases. Because of the expectation of a
very high success rate only the lower 95% CI was of interest (Figure 1). From experience we
knew we could enter approximately 250 patients over an 18-month period. As we wished to
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do two completely independent pilot studies, we chose approximately 120 per group based
on the facts that the sample size was within our capability and that the lower boundary of the
95% CI was less than 7% at any sample size of greater than approximately 80 (i.e., any
sample size greater than 75–80 would have been suitable) (Figure 1). Approximately 120
patients were chosen because it would give a fairly reliable estimate of the true outcome
(i.e., relative narrow 95% CI) and if the true treatment success was ≥95%, that fact would
not likely be missed.

A computer-generated randomization list was used to generate a ‘random sequence and

potential subjects were randomized by an independent staff member and were assigned the
treatments according to consecutive numbers using sealed envelopes. This study was an
open-labeled trial and patients were not blinded. The two studies were otherwise completely
independent.

Secondary outcomes were proportions of adverse events and compliance. To determine the
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independent factors affecting the treatment response, clinical, endoscopic and bacterial
factors are analyzed by Chi-square test with or without Yates correction for continuity and
Fisher’s exact test using the SPSS program (version 10.1, Chicago, Illinois, USA). A P
value ≤0.05 was considered statistically significant. These variables include the following:
age (<60 or ≥60 years), gender, history of smoking (<1 pack/week or ≥1 pack/week), history
of alcohol consumption (<80 g/day or ≥80 g/day), ingestion of coffee (<1 cup/day or ≥1 cup/
day), ingestion of tea (<1 cup/day or ≥1 cup/day), coexistence of a systemic disease (yes or
no), clinical disease (peptic ulcer or functional dyspepsia), adverse event (presence or
absence), drug compliance (good or poor), and antibiotic resistance (presence or absence).
Because case number of the patients with eradication failure in each subgroup was too small,
examination by regression analysis to identify independent factors influencing eradication
outcome was not performed.

Results
Characteristics of the study groups
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A total of 117 H. pylori-infected patients received hybrid therapy. All randomized subjects
were included in the ITT analysis for H. pylori eradication. Data regarding the clinical
characteristics of patients at entry are summarized in Table 1. Among the subjects, six with
poor compliance and two with incomplete follow-up were excluded from PP analysis for H.
pylori eradication.

Antibiotic resistance
H. pylori strains were successfully isolated from 57 (80.3%) of the 71 patients recruited in
the Kaohsiung Veterans General Hospital and the Kaohsiung Medical University. The rates
of resistance were: clarithromycin - 7% (4/57); amoxicillin - 2% (1/57), and metronidazole -
56% (32/57) of the patients, respectively.

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Eradication of H. pylori
Table 2 lists the therapeutic outcomes. The eradication rate according to the PP analyses, H.
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pylori infection was eradicated in (108/109 or 99.1% (95% CI, 98.9% – 100.0%) of those
receiving the hybrid therapy. By ITT analysis treatment success was 114/117 or 97.4% (95%
CI, 94.5% – 100.0%) in hybrid therapy. Hybrid therapy successfully achieved a grade A
eradication outcome using either the PP or the ITT criteria.

Adverse events and compliances

All of the patients received at least one dose of eradication medication and were included in
the adverse event analysis. In total, 14.5% (17/117) of those treated with hybrid therapy
reported at least one adverse event during eradication therapy. The profiles and frequencies
of adverse events are listed in Table 3. Five patients discontinued treatment owing to
adverse events during eradication therapy (diarrhea: 1 patient; dizziness: 1 patient; nausea: 1
patient; vomiting: 1 patient; skin rash: 1 patient).

The percentage of total medication taken by the subjects was 10.7% – 100.0%. Five patients
took less than 90% of the assigned tablets because of severe adverse events, and one patient
forgot to take more than 10% of medicines during anti-H pylori therapy. Overall, six
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patients had poor drug compliance (compliance rate 94.9%).

Factors influence efficacy of eradication with 14-day sequential-concomitant hybrid

therapy
Univariate analysis for the clinical and bacterial factors did not identify any risk factors
associated with treatment failure by sequential-concomitant hybrid therapy (Table 4). The
proportion with H. pylori eradication were similar between those with gastritis only and
those with peptic ulcer subjects (97.0% [32/33] vs. 97.6% [82/84], P = 1.00). Additionally,
all those with amoxicillin-, clarithromycin- and metronidazole-susceptible and resistant
strains (i.e., 32/32 or 100% had H. pylori eradication both by ITT and PP analyses.

Discussion
The fall in H pylori eradication rates with standard triple therapies resulted in a search for
novel therapies for H pylori infections [3]. Here, we tested the hypotheses that extending the
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duration of sequential therapy and continuing the amoxicillin for the full 14 days of therapy
could improve treatment outcome from the typical 90% to 94% to 95% or greater (i.e., from
Grade B to Grade A). We found that the 14-day sequential-concomitant hybrid therapy
produced 99.1% treatment success by PP analysis. The eradication rate by ITT analysis was
97.4% (95% CI, 94.5–100%). In the companion paper, a 14-day sequential therapy achieved
an eradication rate of 93.9% by PP analysis (Grade B success) and 91.9% by ITT analysis.
Taken together, extending sequential therapy to 14-days did not result in a Grade A result.
However, the novel 14-day hybrid therapy could achieve a Grade A success.

In this study, we found no risk factors were associated with treatment failure by univariate
analysis. Specifically, hybrid therapy achieved a high eradication rate for both peptic ulcer
patients and the patients with non-ulcer dyspepsia (97.6% and 97.0%, respectively; P =

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1.00). According to our analysis, there were also no significant relationships in antibiotic
resistance rates between H. pylori strains from NUD and PU patients. However, the numbers
of cases were probably too small to avoid type II error
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One limitation of the current study is that although it was done in three-centers, they were all
in a single country and region of that country and the results will need to be confirmed in
regions where different patterns of resistant are present. Secondly, the numbers of cases with
eradication failure were too small and precluded further regression analyses. Nonetheless,
we confirmed the hypothesis that continuing the amoxicillin through the entire 14 days
resulted in a Grade A result. We are currently investigating whether Grade A success can be
maintained by the hybrid therapies with less than a 14 day treatment duration using 3 pilot
studies evaluating therapies of 10 days (3+7), 12 days (5+7) and 14 days (7+7).

In conclusion, a 14-day sequential-concomitant hybrid therapy achieved Grade A treatment

success for H. pylori eradication. Larger studies and studies in different regions are needed
to confirm this finding and to examine the optimal treatment duration of hybrid therapy.

Acknowledgments
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Declaration of Funding Interests: This study was funded in part by the National Science Council of the ROC
(NSC-98-2314-B-037-004-MY2), Center of Excellence for Environmental Medicine, Kaohsiung Medical
University, National Sun Yat-Sen University-Kaohsiung Medical University Joint Center and AstraZeneca. Role of
the funding source: This study was funded in part by the National Science Council of the ROC (NSC-98-2314-
B-037-004-MY2 and NSC99-2314-B-075B-009) and AstraZeneca. Role of the funding source: Astra provided
support for two technicians but was not involved otherwise in the study specifically no involvement in design or
analysis. Dr Graham is supported in part by Public Health Service grant DK56338 which funds the Texas Medical
Center Digestive Diseases Center and R01 CA116845. The contents are solely the responsibility of the authors and
do not necessarily represent the official views of the VA or NIH. The statistical analysis of the entire data sets
pertaining to efficacy (specifically primary and major secondary efficacy endpoints) and safety (specifically,
serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician who
is not employed by the corporate entity; and the corresponding author had full access to all of the data and takes full
responsibility for the veracity of the data and analysis.

Financial support: The authors disclose the following: In the last 3 years, Dr Graham has received small amounts
of grant support and/or free drugs, or urea breath tests from Meretek, and BioHit for investigator-initiated and
completely investigator-controlled research. Dr Graham is a consultant for Novartis in relation to vaccine
development for treatment or prevention of H pylori infection. Dr Graham is a also a paid consultant for Otsuka
Pharmaceuticals and until July 2007 was a member of the Board of Directors of Meretek Diagnostics, the
manufacturer of the 13C-urea breath test. Dr Graham received royalties on the Baylor College of Medicine patent
covering materials related to 13C-urea breath test until October 2009. Dr PI Hsu and Dr DC Wu have received
small amounts of grant support from AstraZeneca for investigator-initiated and completely investigator-controlled
NIH-PA Author Manuscript

research.

The authors thank Dr Claudia A. Kozinetz for the assistance with study design.

Abbreviations used in this paper

CI confidence interval
ITT intention to treat
H pylori Helicobacter pylori
PP per protocol
PPI proton pump inhibitor

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Antimicrob Chemother. 2009; 63:1017–24. [PubMed: 19246508]
23. Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published
randomised controlled trials. BMJ. 1999; 319:670–4. [PubMed: 10480822]
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Figure 1.
The lower 95% confidence interval is shown for different sample sizes achieving a 98%
treatment success.
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Table 1

Demographic data of the patients

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Characteristics Hybrid therapy (n = 117)

Age (yr) (mean ± SD) 54.3 ± 11.4
Gender (male / female) 59/58
Smoking 19 (16%)
Alcohol consumption 5 (4%)
Ingestion of coffee 26 (22%)
Ingestion of tea 46 (39%)
NSAID user 7 (6%)
Underlying diseases 32 (27%)
Endoscopic Findings
Gastritis 33 (28%)
Gastric ulcer 29 (25%)
Duodenal ulcer 33 (28%)
Gastric ulcer and duodenal ulcer 22 (19%)
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Antibiotic sensitivity a
Clarithromycin (susceptible/resistance) 53/4
Amoxicillin (susceptible/resistance) 56/1
Metronidazole (susceptible/resistance) 25/32

a
Fifty-seven strains were isolated.
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Table 2

The major outcomes of 14-day hybrid therapy

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Parameters of Outcomes Hybrid therapy (n = 117)

Eradication rate
Per-protocol 99.1% (108/109) (97.3% – 100.0%)
Intention-to-treat 97.4% (114/117) (94.5% – 100.0%)
Adverse events 14.5% (17/117) (8.1% – 20.9%)
Compliance 94.9% (111/117) (91.0% – 98.8%)

a
95% confidence interval
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Table 3

Adverse events of 14-day hybrid therapy

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Adverse Events Hybrid therapy (n = 117)

Abdominal pain 4 (1/2/1)
Constipation 0 (0/0/0)
Diarrhea 8 (6/1/1)
Dizziness 6 (4/1/1)
Taste perversion 8 (7/1/0)
Headache 5 (4/1/0)
Anorexia 1 (1/0/0)
Nausea 3 (0/1/2)
Vomiting 2 (0/1/1)
Skin rash 1 (0/0/1)
Fatigue 2 (2/0/0)
Others 4 (2/1/1)

a
Numbers of patients who suffered from mild, moderate and severe adverse events.
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Table 4

Univariate Analysis of the Clinical Factors Influencing the Efficacy of 14-day hybrid Therapy
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Principle parameter No of patients Eradication rate P value

Age 0.55
< 60 y 74 98.6% (73/74)
≥ 60 y 43 95.3% (41/43)
Sex 1.00
Female 59 96.6% (57/59)
Male 58 98.3% (57/58)
Smoking 1.00
 (−) 98 96.9% (95/98)
(+) 19 100.0% (19/19)
Alcohol consumption 1.00
 (−) 112 97.3% (109/112)
(+) 5 100.0% (5/5)
Ingestion of coffee 1.00
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 (−) 91 96.7% (88/91)

(+) 26 100.0% (26/26)
Ingestion of tea 0.28
 (−) 71 96% (68/71)
(+) 46 100.0% (46/46)
NSAID user 1.00
 (−) 110 97.3% (107/110)
(+) 7 100.0%
Underlying diseases 0.18
 (−) 85 98.8% (84/85)
(+) 32 93.8% (30/32)
Gastroduodenal diseases 1.00
Non-ulcer dyspepsia 33 97.0% (32/33)
Peptic ulcer 84 97.6% (82/84)
Adverse event 0.38
 (−) 100 98.0% (98/100)
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(+) 17 94.1% (16/17)

Compliance 1.00
Good 111 97.3% (88/111)
Poor 6 100.0% (6/6)
Antibiotic resistance
Clarithromycin resistance —
susceptible 53 100.0% (53/53)
resistant 4 100.0% (4/4)
Amoxicillin —
susceptible 56 100.0% (56/56)

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Principle parameter No of patients Eradication rate P value

resistant 1 100.0% (1/1)
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Metronidazole resistance —
susceptible 25 100.0% (25/25)
resistant 32 100.0% (32/32)
Presence of any resistant strain —
 (−) 25 100.0% (25/25)
(+) 32 100.0% (32/32)
Dual resistance —
 (−) 53 100.0% (53/53)
(+) 4 100.0% (4/4)
Triple resistance —
 (−) 57 100.0% (57/57)
(+) 0 —

a
Fifty seven strains were isolated.
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