Ef®cacy of sucralfate for Helicobacter pylori eradication tripletherapy in comparison with a lansoprazole-based regimen

K. ADACHI*, S. ISHIHARA*, T. HASHIMOTO  , K. HIRAKAWAà , M. NIIGAKIà , T. TAKASHIMA*,

T. KAJI*, A. KAWAMURA*, H. SATO*, T. OKUYAMA*, M. WATANABE* & Y. KINOSHITA*

*Department of Internal Medicine II, Shimane Medical University, Izumo, Japan;  Unnan General Hospital, Ohhara-gun,

Japan; and àShimane Environment & Health Public Corporation, Shimane Adult Disease Center, Hamada, Japan

Accepted for publication 16 March 2000

INTRODUCTION

Extensive clinical studies of Helicobacter pylori have

shown this bacterium to be an important causative

factor of peptic ulcer, particularly in its recurrence.

Therefore, numerous therapeutic trials for the eradica-

tion of H. pylori have been reported. A recent trend in

curative therapy has been so-called triple therapy, using

a proton pump inhibitor and two different antimicro-

bials.1 Sucralfate, which is a widely used cytoprotective

agent for the gastric mucosa, is reported to inhibit

several of the activities of H. pylori and to enhance the

anti-H. pylori activity of antimicrobial agents.2±11

Therefore, several studies of sucralfate-based eradication

therapy have been reported recently.12±18 However, the

ef®cacy and safety of sucralfate-based therapy are still

controversial.19±20 The present study was designed to

evaluate the ef®cacy and safety of sucralfate in

combination with amoxycillin and clarithromycin as

eradication therapy for H. pylori, in comparison with

lansoprazole-based triple therapy.

PATIENTS AND METHODS

Patients

This study was designed as a prospective, randomized,

multicentre study, and was carried out in accordance

SUMMARY

Background: Sucralfate has an inhibitory action against

Helicobacter pylori and enhances the anti-H. pylori

activity of antimicrobials.

Aim: To evaluate the ef®cacy and safety of sucralfate-

based eradication therapy for H. pylori infection, com-

pared with that based on lansoprazole, in a randomized

multicentre study.

Subjects and methods: The subjects were 150 H. pylori-

positive patients. They were randomly assigned to one

of two regimens for 2 weeks: sucralfate 1 g t.d.s.,

amoxycillin 500 mg t.d.s., and clarithromycin 400 mg

b.d. (SAC regimen: 75 patients); or lansoprazole 30 mg

o.m. with the same antimicrobial medications (LAC

regimen: 75 patients). Cure of infection was assessed

by a 13C urea breath test 1 month after completion of

treatment.

Results: Eight patients (four in the SAC group and four

in LAC group) could not continue therapy because of

severe diarrhoea, and three did not take the 13C urea

breath test after therapy. Cure rates for intention-to-

treat, all-patients-treated, and per protocol analysis in

the SAC group were 80%, 83%, and 88%, respectively,

and those in the LAC group were 87%, 87%, and 92%,

respectively. There were no signi®cant differences in

cure rate or adverse effects between the two regimens.

Conclusion: Sucralfate in combination with amoxycillin

and clarithromycin is as effective as lansoprazole-based

eradication therapy for H. pylori.

Correspondence to: Dr K. Adachi, Department of Internal Medicine II,

Shimane Medical University, 89-1 Enya-cho, Izumo-shi, Shimane 693±

8501, Japan.E-mail: kadachi@shimane-med.ac.jp

Aliment Pharmacol Ther 2000; 14: 919±922.

Ó 2000 Blackwell Science Ltd 919

with the Declaration of Helsinki. The study subjects

were 150 H. pylori-positive patients, who had under-

gone eradication therapy at three medical centres

(Shimane Medical University, Unnan General Hospital,

and Shimane Adult Disease Center, Hamada) between

August 1998 and October 1999. None of the patients

had undergone previous eradication therapy and/or

gastric surgery at these medical centres or other clinics.

Patients with malignant, severe heart, liver, renal, and/

or haematological disease or who were pregnant and

lactating, were excluded. At each medical centre, 50

consecutive patients were enrolled. All patients under-

went a physical examination and gave their informed

consent before study enrolment. There were 112 men

and 38 women, with a mean age of 51.7 � 13.0 years

(range, 16±81 years), comprising 65 patients with

gastric ulcer (or ulcer scar), 56 patients with duodenal

ulcer (or ulcer scar), 18 patients with gastroduodenal

ulcer (or ulcer scar), three patients who had received

endoscopic treatment for early gastric cancer, four

patients with gastric hyperplastic polyps, and four

patients with gastritis accompanied by severe dyspepsia

(Table 1). They were randomly assigned to one of the

following two regimens for 2 weeks, encoded in an

envelope: each group of 75 patients received either

sucralfate suspension 1 g t.d.s. between meals and at

bedtime (SAC regimen); or lansoprazole 30 mg o.m.

30 min after breakfast (LAC regimen), both regimens

being in combination with amoxycillin 500 mg t.d.s.

and clarithromycin 400 mg b.d., 30 min after meals.

The characteristics of the patients in each group are

shown in Table 1.

Methods

Before receiving therapy, all patients underwent upper

gastrointestinal endoscopy to con®rm the presence of

H. pylori infection and the diagnosis. H. pylori status was

diagnosed by the rapid urease test, histology (Warthin±

Starry silver staining), culture, serology (serum IgG

antibody), and/or the 13C urea breath test. The patients

were diagnosed as H. pylori positive when they showed

positive results by at least two methods.

Possible eradication of H. pylori was assessed by the13C urea breath test 1 month (4±6 weeks) after com-

pletion of the treatment; following completion of the

treatment, proton pump inhibitors and antimicrobials

that might have affected the 13C urea breath test were

not given to these patients. The 13C urea breath test was

performed as described previously, with minor modi®-

cations.21 In brief, patients were fasted for 12 h before

the examination. 13C-Urea (100 mg) dissolved in dis-

tilled water was administered. Patients were instructed

to maintain a left-lateral recumbent position for 5 min,

followed by a sitting position for 15 min. Breath

samples before and 20 min after administration of13C-urea were collected after a mouthwash. The 13C-

urea concentration in breath samples was measured by

a 13C analyser (ABCA-G, European Scienti®c, Crewe,

UK). Patients whose D13C value was lower than 5&were regarded as successfully cured.

The cure rate was de®ned as the number of success-

fully treated patients divided by the total number of

treated patients. Cure rates were evaluated by intention-

to-treat (ITT), all-patients-treated (APT), and per proto-

col (PP) analyses. Patients were interviewed at their ®rst

visit to the clinic after completion of the therapy, to

clarify compliance with the therapy and any adverse

effects. The compliance was assessed by counting the

number of residual drugs used for the treatment after

completion of the therapy.

Statistical analysis

The v2-test and Mann±Whitney test were used to

compare the two regimens. Differences at P < 0.05

were considered statistically signi®cant.

RESULTS

Each group of 75 patients was treated with either the

SAC or the LAC regimen. The underlying diseases from

Table 1. Patient characteristics

SAC regimen

(n = 75)

LAC regimen

(n = 75)

Total

(n = 150)

Male/female 57/18 55/20 112/38

Age (mean � s.d.) 50.5 � 12.9 53.0 � 13.1 51.7 � 13.0

Gastric ulcer 34 31 65

Duodenal ulcer 29 27 56

Gastroduodenal

ulcers

10 8 18

Gastric cancer* 1 2 3

Gastric polyp 0 3 3

Gastritis with

dyspepsia

1 3 4

SAC: sucralfate, amoxycillin, and clarithromycin; LAC: lansoprazole,

amoxycillin, and clarithromycin.*Patients who had received endoscopic treatment for early gastric

cancer.

920 K. ADACHI et al.

Ó 2000 Blackwell Science Ltd, Aliment Pharmacol Ther 14, 919±922

which patients in each group were suffering are shown

in Table 1. There were no signi®cant differences in

endoscopic diagnosis, patient age, or gender between

these two groups.

There was no signi®cant difference in the occurrence of

adverse effects between the two groups. Eight patients

(four in the SAC group, four in the LAC group) did not

complete the treatment because of severe diarrhoea

with abdominal pain. No other severe side-effect was

observed. Seven patients in the SAC group and eight in

the LAC group reported soft stools, and six patients in

the SAC group and ®ve in the LAC group reported

glossitis or taste disturbance. All of these 26 patients

with mild adverse effects completed the therapy. Three

patients in the SAC group did not undergo the 13C urea

breath test after therapy; 139 patients, excluding eight

with incomplete treatment and the three who did not

undergo the 13C urea breath test after treatment, took

almost all (95±100%) of the prescribed medication.

Therefore, 147 patients were included in ATT analysis,

and 139 patients in PP analysis. The cure rates for each

therapeutic regimen are listed in Table 2. There was no

signi®cant difference in the cure rates determined by all

analyses between the two regimens.

DISCUSSION

A recent trend in eradication therapy for H. pylori is the

so-called triple therapy, consisting of a proton pump

inhibitor and two antimicrobial agents.1 Many different

therapeutic regimens using this combination have been

tried in order to ®nd the optimal drugs, dosages and

treatment duration.

Sucralfate has local cytoprotective activity for the

gastric mucosa, but is not absorbed into the systemic

circulation. Recent studies have demonstrated that

sucralfate has anti-H. pylori activities. In vitro studies

have shown that sucralfate inhibits the haemaggluti-

nin, mucolytic, protolytic, lipolytic, and urease activities

of H. pylori.2±6 In addition, it also suppresses H. pylori-

related toxic substances that may aggravate duodenal

mucosal injury.7 In vivo studies have con®rmed that

sucralfate reduces the density of H. pylori in the

stomach.8±10 Sucralfate is also reported to enhance

the anti-H. pylori activity of metronidazole, erythromy-

cin, tetracycline, and amoxycillin.11 Against this

background, several studies have evaluated a sucral-

fate-based eradication therapy for H. pylori infection,

and good tolerance to the therapy has been clari®ed.12±18

However, eradication rates for sucralfate-based triple

therapies have ranged from 59% to 100%, and the

ef®cacy of sucralfate for H. pylori eradication therapy

seems to be questionable.19±20 Furthermore, only a

single study has compared the eradication rate of

sucralfate-based triple therapy with that of proton

pump inhibitor-based triple therapy.13 In that study,

the eradication rate was 86% after 4 weeks of therapy

with sucralfate 1 g q.d.s. in combination with clari-

thromycin 250 mg q.d.s. and metronidazole 300 mg

q.d.s., and was 87% for omeprazole 20 mg b.d. with the

same antimicrobials for the same period. Furthermore,

the number of investigated subjects was only 69, and

the eradication of H. pylori was assessed only by the

rapid urease test, using gastric antral biopsy specimens.

Although the rapid urease test is useful for the diagnosis

of H. pylori infection before eradication therapy, its

sensitivity is too low for the con®rmation of H. pylori

eradication after therapy. Furthermore, one biopsy-

based test is not adequate for con®rming eradication,

whereas the 13C urea breath test can be used on its

own.21±26 Our study is the ®rst investigation of

sucralfate-based eradication in which the cure of

H. pylori infection was assessed by the reliable 13C urea

breath test. Our ®ndings con®rmed that sucralfate-based

eradication therapy is an effective proton pump inhib-

itor-based treatment. The majority of the recently

recommended eradication therapy regimens are 1 week

in duration, since 1-week-long therapies have advant-

ages in compliance and medical cost, with a similar

eradication rate. This good eradication rate may be

expected after a 1-week-long sucralfate-based triple

therapy although it is not investigated in this study.

Further study is necessary to investigate the appropriate

length of sucralfate-based triple therapy for the cost-

effective eradication of H. pylori. As sucralfate does not

Table 2. Cure rate for each regimen

SAC regimen LAC regimen v2-test

ITT 80 87 N.S.

71±89 79±95

ATT 83 87 N.S.

75±92 79±95

PP 88 92 N.S.

80±96 85±98

ITT: intention-to-treat analysis; APT: all-patients-treated analysis;

PP: per protocol analysis.

Cure rate is given with the 95% con®dence interval.

EFFICACY OF SUCRALFATE FOR H. PYLORI ERADICATION 921

Ó 2000 Blackwell Science Ltd, Aliment Pharmacol Ther 14, 919±922

have any systemic activity, a low occurrence rate of

adverse effects was expected. However, there was no

signi®cant difference between the adverse effects of

sucralfate- and lansoprazole-based regimens. Accord-

ingly, the adverse effects of triple therapy using a

combination of two antimicrobials may have been due

mainly to the antimicrobials used.

In conclusion, the ef®cacy and tolerance of sucralfate

in combination with amoxycillin and clarithromycin for

H. pylori eradication are equal to those of lansoprazole-

based therapy.

ACKNOWLEDGEMENTS

We wish to thank Ms Rika Tohma, Ms Kiyoe Ueda, and

Ms Keiko Masuzaki for their technical support.

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