Clinical trial NCT00455806: Esomeprazole, Moxifloxacin and Amoxicilin for Rescue Therapy of Helicobacter Pylori Infection
Official title: Randomized, Controlled, Multicenter Phase III Study for the Efficacy and Tolerability of Triple Therapy With Esomeprazole, Moxifloxacin and Amoxicillin for Rescue Therapy of Helicobacter Pylori Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Helicobacter Pylori Infection
Chronic Gastritis
Keywords: Helicobacter pylori
rescue therapy
eradication therapy
esomeprazole
moxifloxacin
resistance
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2007-04-04
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Successful H. pylori eradication therapy remains a challenge in medical practice. Despite promising data for first-line, second-line and rescue treatment options based on clinical trials as well as guidelines and expert recommendations, success rates can often not be reproduced in general practice. Rescue options for patients with failed initial or second-line therapy are definitely needed. The new fluoroquinolone moxifloxacin may represent an effective and save treatment option (in combination with a PPI and amoxicillin) for rescue therapy of H- pylori positive patients.However, optimal duration of therapy (7-day course vs 14-day course) has to be determined

Detailed description: Successful H. pylori eradication therapy remains a challenge in medical practice. Currently, a PPI - based triple therapy containing clarithromycin, amoxicillin or nitroimidazole given for 7 days is the recommended first line treatment approach with an expected eradication success rate of approximately 80%. As second-line treatment option in case of failure, a RBC-based quadruple therapy is currently recommended curing another 80% of patients, leaving a subset of patients with persistent H. pylori infection. Resistance to fluoroquinolones is low in most countries,hence these compounds are potential candidates for second-line and rescue treatment. The new fluoroquinolone moxifloxacin launched by Bayer in 1999 for the treatment of respiratory tract infections, has a broad antibacterial spectrum comparable to levofloxacin but fewer phototoxic and central nervous system excitatory effects. The possible role of moxifloxacin in H. pylori eradication is since under clinical investigation

Eligibility criteria: Inclusion Criteria:

* male/female, age \>/=18 years
* Helicobacter pylori infection proven by histology and culture
* indication for eradication therapy according to the Maastricht-III
* at least one failed prior eradication attempt
* pretherapeutic resistance testing (culture)
* written informed consent

Exclusion Criteria:

* in vitro resistance to moxifloxacin or amoxicillin
* current complicated peptic ulcer disease
* daily intake of NSAIDs
* co-medication with drugs known to interact with the study medication
* history of gastric surgery/vagotomy
* medical treatment for depression, known suicide attempt
* severe cardiological diseases such as bradyarrythmia, QT changes
* malignant disease
* gravidity, nursing
* women with child bearing potential must perform contraceptive measures

Primary outcomes:
measure: Efficacy of a combination of esomeprazole (E), moxifloxacin (M) and amoxicillin (A) for third line therapy of H. pylori infection.
measure: Comparison of EMA 7 days versus EMA 14 days. Hypothesis: superiority of EMA 14 days 4 weeks after end of eradication therapy
Secondary outcomes:
measure: Tolerability,safety, post treatment resistance, influence of host genetics (CYP status) and pathogenicity factors of H. pylori on treatment success.
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Gastroenterologist, private praxis
city: Dresden
country: Germany
facility: Med. Dept. I, Gastroenterology, University Hospital, Technical University of Dresden
city: Görlitz
country: Germany
facility: Gastroenterologist / private praxis
city: Homburg/Saar
country: Germany
facility: Medical Department, University Homburg/Saar
city: Kiel
country: Germany
facility: Medical Dept. I, University Hpspital Kiel
city: Munich
country: Germany
facility: Gastroenterologist / private praxis
city: Munich
country: Germany
facility: Technical University of Munich, Medical Dept. II
city: Oldenburg
country: Germany
facility: Gastroenterologist / private praxis
city: Siegen
country: Germany
facility: Med. Department, Jung-Stilling Krankenhaus
Study officials:
affiliation: Medical Department I, Gastroenterology, Universityhospital, Technical University Dresden
name: Stephan Miehlke, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institue for Medical Microbiology, University of Regensburg
name: Norbert Lehn, MD, PhD
role: STUDY_CHAIR
affiliation: Institute for Medical Microbiology, Technical University of Dresden
name: Enno Jacobs, MD, PhD
role: STUDY_CHAIR
affiliation: Institute for Pathology, Klinikum Bayreuth
name: Manfred Stolte, MD, PhD
role: STUDY_CHAIR
References:
citation: Morgner A, Labenz J, Miehlke S. Effective regimens for the treatment of Helicobacter pylori infection. Expert Opin Investig Drugs. 2006 Sep;15(9):995-1016. doi: 10.1517/13543784.15.9.995.
citation: Miehlke S, Hansky K, Schneider-Brachert W, Kirsch C, Morgner A, Madisch A, Kuhlisch E, Bastlein E, Jacobs E, Bayerdorffer E, Lehn N, Stolte M. Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment Pharmacol Ther. 2006 Jul 15;24(2):395-403. doi: 10.1111/j.1365-2036.2006.02993.x.
citation: Miehlke S, Schneider-Brachert W, Bastlein E, Ebert S, Kirsch C, Haferland C, Buchner M, Neumeyer M, Vieth M, Stolte M, Lehn N, Bayerdorffer E. Esomeprazole-based one-week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance. Aliment Pharmacol Ther. 2003 Oct 15;18(8):799-804. doi: 10.1046/j.1365-2036.2003.01764.x.
citation: Miehlke S, Bayerdorffer E, Graham DY. Treatment of Helicobacter pylori infection. Semin Gastrointest Dis. 2001 Jul;12(3):167-79.
citation: Cheon JH, Kim N, Lee DH, Kim JM, Kim JS, Jung HC, Song IS. Efficacy of moxifloxacin-based triple therapy as second-line treatment for Helicobacter pylori infection. Helicobacter. 2006 Feb;11(1):46-51. doi: 10.1111/j.0083-8703.2006.00371.x.
citation: Nista EC, Candelli M, Zocco MA, Cazzato IA, Cremonini F, Ojetti V, Santoro M, Finizio R, Pignataro G, Cammarota G, Gasbarrini G, Gasbarrini A. Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2005 May 15;21(10):1241-7. doi: 10.1111/j.1365-2036.2005.02412.x.
citation: Di Caro S, Ojetti V, Zocco MA, Cremonini F, Bartolozzi F, Candelli M, Lupascu A, Nista EC, Cammarota G, Gasbarrini A. Mono, dual and triple moxifloxacin-based therapies for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2002 Mar;16(3):527-32. doi: 10.1046/j.1365-2036.2002.01165.x.
citation: Megraud F, Lamouliatte H. Review article: the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther. 2003 Jun 1;17(11):1333-43. doi: 10.1046/j.1365-2036.2003.01592.x.