Esomeprazole, Moxifloxacin and Amoxicilin for Rescue Therapy of Helicobacter Pylori Infection (ESAMOX)

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

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

Study Overview

• Status: Unknown
• Conditions: Helicobacter Pylori Infection; Chronic Gastritis
• Intervention / Treatment: Drug: esomeprazole; Drug: moxifloxacin; Drug: amoxicillin

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

• Study Type: Interventional
• Enrollment: 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany, 51063
    • Recruiting
    • Gastroenterologist, private praxis
    • Contact: Elke Bästlein, MD
    • Principal Investigator: Elke Bästlein, MD
  • Dresden, Germany
    • Recruiting
    • Med. Dept. I, Gastroenterology, University Hospital, Technical University of Dresden
    • Contact: Andrea Morgner-Miehlke, MD, PhD
    • Principal Investigator: Andrea Morgner-Miehlke, MD, PhD
  • Görlitz, Germany
    • Recruiting
    • Gastroenterologist / private praxis
    • Contact: Christian Haferland, ME
    • Principal Investigator: Christian Haferland, MD
  • Homburg/Saar, Germany
    • Recruiting
    • Medical Department, University Homburg/Saar
    • Contact: Gerhard Treiber, MD, PhD
    • Principal Investigator: Gerhard Treiber, MD, PhD
  • Kiel, Germany
    • Recruiting
    • Medical Dept. I, University Hpspital Kiel
    • Contact: Stefan Hellmig, MD, PhD
    • Principal Investigator: Stefan Hellmig, MD, PhD
  • Munich, Germany
    • Recruiting
    • Gastroenterologist / private praxis
    • Contact: Wilfried Höchter, MD
    • Contact: Josef Weingart
    • Principal Investigator: Wilfried Höchter, MD
  • Munich, Germany
    • Recruiting
    • Technical University of Munich, Medical Dept. II
    • Contact: Alexander Meining, MD, PhD
    • Principal Investigator: Alexander Meining, MD, PhD
  • Oldenburg, Germany
    • Recruiting
    • Gastroenterologist / private praxis
    • Contact: Michael Neumeyer, MD
    • Principal Investigator: Michael Neumeyer, MD
  • Siegen, Germany
    • Recruiting
    • Med. Department, Jung-Stilling Krankenhaus
    • Contact: Andreas Leodolter, MD
    • Contact: Joachim Labenz, MD, PhD
    • Principal Investigator: Andreas Leodolter, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Efficacy of a combination of esomeprazole (E), moxifloxacin (M) and amoxicillin (A) for third line therapy of H. pylori infection.
Comparison of EMA 7 days versus EMA 14 days. Hypothesis: superiority of EMA 14 days 4 weeks after end of eradication therapy

Secondary Outcome Measures

Outcome Measure
Tolerability,safety, post treatment resistance, influence of host genetics (CYP status) and pathogenicity factors of H. pylori on treatment success.

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Investigators: Principal Investigator: Stephan Miehlke, MD, PhD, Medical Department I, Gastroenterology, Universityhospital, Technical University Dresden; Study Chair: Norbert Lehn, MD, PhD, Institue for Medical Microbiology, University of Regensburg; Study Chair: Enno Jacobs, MD, PhD, Institute for Medical Microbiology, Technical University of Dresden; Study Chair: Manfred Stolte, MD, PhD, Institute for Pathology, Klinikum Bayreuth

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• Miehlke S, Bayerdorffer E, Graham DY. Treatment of Helicobacter pylori infection. Semin Gastrointest Dis. 2001 Jul;12(3):167-79.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Study Completion (Anticipated): February 1, 2008

Study Registration Dates

• First Submitted: April 3, 2007
• First Submitted That Met QC Criteria: April 3, 2007
• First Posted (Estimate): April 4, 2007

Study Record Updates

• Last Update Posted (Estimate): April 4, 2007
• Last Update Submitted That Met QC Criteria: April 3, 2007
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: Helicobacter pylori; esomeprazole; resistance; eradication therapy; rescue therapy; moxifloxacin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gastritis; Infections; Communicable Diseases; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Moxifloxacin; Amoxicillin; Esomeprazole
• Other Study ID Numbers: ESAMOX_01_2007; EudraCT Numberr 2006-004323-10