Summary
Background: It is well established that a
7-day triple therapy achieves eradication rates of Helicobacter pylori between
90 %
and 95 %. Due to a lack of highly effective short-term eradication studies the
aim of
the present pilot study was to investigate the effect of a 4-day triple therapy
with the new proton
pump inhibitor rabeprazole (20 mg b. i. d. ) in combination with
clarithromycin (500 mg b. i. d. ) and amoxicillin
(1 g b. i. d. ) without acid-suppressive pre-treatment in
patients with H. pylori-related peptic ulcer disease.
Methods: 20
patients (11 men, 9 women) with endoscopically diagnosed peptic ulcers (gastric
ulcer:
n = 5; duodenal ulcer: n = 9; combined gastric and
duodenal ulcer: n = 2, gastric or duodenal ulcer scars:
n = 4) and H. pylori infection were consecutively recruited. The Helicobacter
pylori status was assessed by means of histology, CLO (urea-) test and C13 -urea breath
test (C13 -UBT) at entry. Treatment success was determined by C13 -UBT
35-42 days after end of treatment.
Results: In 18 out of the
20 patients (90 %) [77-100 %, 95 %-CI] a
negative test result was found in C13 -UBT 35-42 days after treatment. The 2
patients who remained H. pylori-positive had a duodenal ulcer.
Conclusion: A 4-day triple therapy of rabeprazole in combination with
clarithromycin and amoxicillin seems to be highly effective in eradicating H.
pylori and well
tolerated in patients with gastric and duodenal ulcer disease. The achieved eradication
rate of
90 % is comparable with the established 7-day triple therapy regimens. On the
basis
of these results and considering costs, side effects and compliance a large number
of patients
should be enrolled in a confirmatory 4-day eradication trial.
4-tägige Eradikationstherapie mit Rabeprazol, Amoxicillin und Clarithromycin bei
Patienten mit peptischer Ulkuserkrankung und Helicobacter-pylori-Infektion - eine
Pilotstudie
Hintergrund/Ziel: Aufgrund der nur spärlichen
Datenlage zur Kurzzeiteradikation war es das Ziel dieser Pilotstudie, die Wirksamkeit
einer
4-tägigen Eradikationstherapie mit dem neuen Protonenpumpeninhibitor Rabeprazol
(2 × 20 mg/d) in Kombination mit Clarithromycin
(2 × 500 mg/d) und Amoxicillin (2 × 1 g/d) an
20 Patienten mit Helicobacter pylori-assoziierten peptischen Ulzera zu untersuchen.
Methoden: 20 Patienten (11 Männer, 9 Frauen) mit endoskopisch
gesichertem peptischem Ulkus (Ulcus ventriculi: n = 5, Ulcus duodeni:
n = 9, Ulcus ventriculi et duodeni: n = 2, Ulkunisnarben:
n = 4) und Helicobacter-pylori-Infektion wurden in die Studie eingeschlossen.
Die Infektion Mit Helicobacter pylori wurde histologisch durch den Urease-Schnelltest
(CLO-Test)
und im 13 C-Harnstoff-Atemtest bei Studienbeginn gesichert. Der Behandlungserfolg wurde
im 13 C-Harnstoff-Atemtest 35-42 Tage nach Behandlung gemessen. Ergebnis: Von den 20 Patienten hatten 18 Patienten (90 %) ein
negatives Ergebnis im 13 C-Harnstoff-Atemtest nach Eradikationstherapie. Die beiden
Patienten mit positivem Atemtest hatten bei Einschluss in die Studie ein Ulcus
duodeni. Die
Therapie wurde allgemein gut vertragen, schwer wiegende unerwünschte Ereignisse
traten
während der Studiendauer nicht auf. Schlussfolgerung: Eine
4-tägige Kurzzeit-Tripeltherapie mit Rabeprazol (2 × 20 mg/d) in
Kombination mit Clarithromycin (2 × 500 mg/d) und Amoxicillin
(2 × 1 g/d) ist mit einer Erfolgsrate von 90 % hoch
wirksam in der Eradikation von Helicobacter pylori bei Patienten mit peptischer
Ulkuserkrankung und
mit den Ergebnisse der etablierten 7-tägigen Tripeltherapien vergleichbar. Die
Ereignisse
dieser Pilotstudie sollten zu einer größeren, kontrollierten Multizenterstudie
auffordern, um bei Bestätigung der vorliegenden Ergebnisse die Behandlungskosten
einer
Eradikationstherapie zu erniedrigen und die Patientencompliance zu erhöhen.
Key words
Eradication - Triple
Therapy - Rabeprazole - Short-term - Helicobacter pylori
Schlüsselwörter
Eradikation - Tripeltherapie - Kurzzeit - Rabeprazol - Helicobacter
pylori
Literature
1
Tytgat G NJ.
Working party report to the World Congress of Gastroenterology, Sydney
1990.
J Gastroenterol
Hepatol.
1991;
6
139-140
2
NIH Consensus Conference .
Helicobacter pylori in peptic ulcer disease.
NIH Consensus Development
Panel on Helicobacter pylori in Peptic Ulcer
Disease.
1994;
272
65-69
3
Unge P, Gad A, Eriksson K. et al .
Amoxicillin added to omeprazole prevents relapse in the treatment of duodenal
ulcer patients.
Eur J Gastroenterol
Hepatol.
1993;
5
325-331
4
Kuipers E J.
Helicobacter pylori and the risk and management of associated diseases:
Gastritis, ulcer disease, atrophic gastritis and gastric cancer.
Aliment Pharmacol
Ther.
1997;
11 (Suppl.
1)
71-88
5
Stack W A, Knifton A, Thirlwell D. et al .
Safety and efficacy of rabeprazole in combination with four antibiotic regimens
for the eradication of Helicobacter pylori in patients with chronic gastritis
with or without
peptic ulceration.
Am J
Gastroenterol.
1998;
93
1909-1913
6
De
Boer W A, Driessen W M, Potters V P. et al .
Randomized study comparing 1 with 2 weeks of quadruple therapy for eradicating
Helicobacter pylori.
Am J
Gastroenterol.
1994;
89
1993-1997
7
Bazzoli F, Zagari R M, Fossi S. et al .
Efficacy and tolerability of a short-term, low-dose triple therapy for
eradication of Helicobacter
pylori.
Gastroenterology.
1993;
104
A-10
(Abstract)
8
Grimley C E, Penny A, O’Sullivan M. et al .
Comparison of two 3-day Helicobacter pylori eradication regimens with a standard
1-week regimen.
Aliment Pharmacol
Ther.
1999;
13
869-873
9
O’Riordan T, Mathai E, Tobin E. et al .
Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth
subcitrate.
Gut.
1991;
31
999-1002
10
Dekkers C PM, Beker J A, Thjodleifsson B. et al .
Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the
treatment of active gastric ulcer - a European multicentre study.
Aliment Pharmacol
Ther.
1998;
12
789-795
11
Dekkers C PM, Beker J A, Thjodleifsson B. et al .
Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the
treatment of active duodenal ulcer: A European multicentre study.
Aliment Pharmacol
Ther.
1999;
13
179-186
12
Dekkers C PM, Beker J A, Thjodleifsson B. et al .
Double-blind comparison of rabeprazole 20 mg vs. omeprazole 20 mg
in the treatment of erosive or ulcerative gastro-oesophageal reflux disease.
Aliment
Pharmacol
Ther.
1999;
13
49-57
13
Pantoflickova D, Dorta G, Jornod P. et al .
Identification of the characteristics influencing the degree of antisecretory
activity of PPIs.
Gastroenterology.
2000;
118 (Suppl.
2)
A1290 (Abstract)
14
Trevisani L, Sartori S, Galvani F. et al .
Evaluation of a new ultrashort triple therapy for Helicobacter pylori
disease.
Aliment Pharmacol
Ther.
1998;
12
1269-1272
15
Treiber G, Treating H.
pylori shorter than one week - a real future perspective?.
Z
Gastroenterol.
2000;
38
807-812
16
McNulty C A, Dent J C, Ford G A. et al .
Inhibitory antimicrobial concentrations against Campylobacter pylori in gastric
mucosa.
J Antimicrob
Chemother.
1988;
22
729-738
17
Tsuji A, Nakashima E, Hamano S. et al .
Physicochemical properties of amphoteric beta-lactam antibiotics. I: Stability,
solubility, and dissolution behavior of amino penicillins as a function of pH.
J Pharm
Sci.
1978;
67
1059-1066
18
Iwahi T, Satoh H, Nakao M. et al .
Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related
compounds have selective activity against Helicobacter pylori.
Antimicrob Agents
Chemother.
1991;
35
490-496
19
Bunoli M, Bayelli P F, Rappuoli R. et al .
Inhibition of Helicobacter pylori urease by omeprazole.
Eur J
Gastroenterol
Hepatol.
1993;
5
683-685
20
Tsuchiya M, Imamura L, Park J B. et al .
Helicobacter pylori urease inhibition by rabeprazole, a proton pump
inhibitor.
Biol Pharm
Bull.
1995;
18
1053-1065
21
Park J B, Imamura L, Kobashi K.
Kinetic studies of Helicobacter pylori urease inhibition by a novel proton pump
inhibitor, rabeprazole.
Biol Pharm
Bull.
1996;
19
182-187
22
De
Boer W, Driessen W, Jansz A. et al .
Effect of acid suppression on efficacy of treatment for Helicobacter pylori
infection.
Lancet.
1995;
345
817-820
23
Treiber G, Ammon S, Schneider E. et al .
Amoxicillin/metronidazole/omeprazole/clarithromycin: A new, short quadruple
therapy for Helicobacter pylori
eradication.
Helicobacter.
1998;
3
54-58
24
Bazzoli F, Zagari R M, Pozzato P. et al .
Helicobacter pylori: Optimum diagnosis and test of cure.
J
Chemother.
1999;
11
601-605
25
Frevel M, Daake H, Janisch H D. et al .
Eradication of Helicobacter pylori with pantoprazole and two antibiotics: A
comparison of two short-term regimens.
Aliment Pharmacol
Ther.
2000;
14
1151-1157
26
De
Boer W A, Driessen W M, Tytgat G N.
Only four days of quadruple therapy can effectively cure Helicobacter pylori
infection.
Aliment Pharmacol
Ther.
1995;
9
633-638
27
De Boer W A, van
Etten R J, Schade R W. et al .
4-day lansoprazole quadruple therapy: A highly effective cure for Helicobacter
pylori infection.
Am J
Gastroenterol.
1996;
91
1778-1782
28
De
Boer S Y, Siem T H.
Four-day quadruple therapy as a routine treatment for Helicobacter pylori
infection.
Aliment Pharmacol
Ther.
1997;
11
1119-1121
29
De Boer W A, van
Etten R J, Schneeberger P M.
Four-day lansoprazole-quadruple therapy in the routine treatment of Helicobacter
pylori infection.
Neth J
Med.
1998;
52
10-15
30
Lai J Y, De
Boer W A, Driessen W M. et al .
Long-term follow-up after cure of Helicobacter pylori infection with 4 days of
quadruple therapy.
Aliment Pharmacol
Ther.
1996;
10
645-650
31
De Boer W A, van
Etten R J, Coremans A. et al .
Two-day „weekend” lansoprazole-quadruple therapy for Helicobacter
pylori infection.
Aliment Pharmacol
Ther.
1998;
12
77-81
32
Kung N S, Sung J JY, Ng P W. et al .
Two-day versus one-week anti-Helicobacter therapy in controlled bleeding ulcers:
A prospective randomized trial.
Gut.
1996;
39
(Suppl.)
A32 (Abstract)
33
Tucci A, Poli L, Paparo F. et al .
Weekend therapy for the treatment of Helicobacter pylori infection.
Am
J
Gastroenterol.
1998;
93
737-742
34
Tucci A, Corinaldesi R, Stanghellini V. et al .
One-day therapy for treatment of Helicobacter pylori infection.
Dig Dis
Sci.
1993;
38
1670-1673
35
Ladas S D, Malamou-Lada H, Economou G. et al .
A three-day octreotide-containing Helicobacter pylori eradication therapy for
cure of peptic
ulcers.
Hepatogastroenterology.
1998;
45
761-764
36
Calvet X, Tito L, Comet R. et al .
Four-day, twice daily, quadruple therapy with amoxicillin, clarithromycin,
tinidazole and omeprazole to cure Helicobacter pylori infection: A pilot
study.
Helicobacter.
2000;
5
52-56
37
Coelho L G, Passos M C, Chausson Y. et al .
Five-day bismuth-free triple therapy for the eradication of Helicobacter pylori
and reduction of duodenal ulcer relapse.
Am J
Gastroenterol.
1991;
86
971-975
38
Sheu B S, Yang H B, Su I J. et al .
A three-day course of intravenous omeprazole plus antibiotics for H.
pylori-positive bleeding duodenal ulcer.
Gut.
1996;
39
(Suppl.)
A32 (Abstract)
39
Seelis R E, Dohmen W.
Short-term (6 days) eradication of Helicobacter pylori infection in the practice
of a health insurance physician.
Dtsch Med
Wochenschr.
1998;
123
103-108
Address for correspondence
Manfred V. Singer MD
Professor of Medicine and Chairman Department of Medicine
IV (Gastroenterology and Hepatology) University Hospital of Heidelberg at
Mannheim
Theodor-Kutzer-Ufer
68135 Mannheim
Email: Manfred.V.Singer@med4.ma.uni-heidelberg.de