Comparison of Two Antibiotic Regimen (Meropenem Versus Meropenem+Moxifloxacin)in the Treatment of Severe Sepsis and Septic Shock

NCT ID: NCT00534287

Last Updated: 2012-06-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2010-06-30

Brief Summary

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Severe sepsis and septic shock are diseases of infectious origin with a high risk of death. Antibiotic therapy is mandatory but it is unknown whether one antibiotic alone is sufficient for initial therapy. The purpose of this study is to compare a therapy with meropenem alone or the combination of meropenem plus moxifloxacin in the treatment of severe sepsis/ septic shock. Patients randomly receive one of the two treatments for at least 7 days but not longer than 14 days.

Detailed Description

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Early intravenous empiric broad-spectrum antimicrobial therapy is an essential part of sepsis therapy. Inadequacy of empirical antibiotic therapy is associated with an increased mortality rate. Carbapenems are designed for empirical antimicrobial monotherapy. Combination therapy has been suggested but efficiency remains to be proven. In this study, antimicrobial monotherapy with meropenem is compared with a combination therapy of meropenem and moxifloxacin. It is hypothesized that the superior antibiotic therapy is associated with a lower overall organ dysfunction in sepsis. Study therapy lasts for at least 7 days unless microbiological results suggest otherwise. Study therapy may be extended to 14 days. Follow up examinations occur at 28 and 90 days. This investigator initiated study is supported by the German government (bmbf) and unrestricted industrial grants.

Conditions

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Severe Sepsis Septic Shock

Keywords

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sepsis antibiotics carbapenems fluoroquinolones Severe sepsis and septic shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MeroMono

Monotherapy with meropenem

Group Type ACTIVE_COMPARATOR

meropenem

Intervention Type DRUG

Empirical antibiotic therapy with 3 x 1 g intravenous meropenem. Dosage is adjusted in case of renal dysfunction. Recommended duration of therapy is 7 days but can be extended up to 14 days.

MeroMoxi

Combination therapy with meropenem + moxifloxacin

Group Type ACTIVE_COMPARATOR

meropenem, moxifloxacin

Intervention Type DRUG

Empirical antibiotic therapy with 3 x 1 g intravenous meropenem plus 1 x 400 mg intravenous moxifloxacin. Dosage of meropenem is adjusted in case of renal dysfunction. Recommended duration of therapy is 7 days but can be extended up to 14 days.

Interventions

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meropenem

Empirical antibiotic therapy with 3 x 1 g intravenous meropenem. Dosage is adjusted in case of renal dysfunction. Recommended duration of therapy is 7 days but can be extended up to 14 days.

Intervention Type DRUG

meropenem, moxifloxacin

Empirical antibiotic therapy with 3 x 1 g intravenous meropenem plus 1 x 400 mg intravenous moxifloxacin. Dosage of meropenem is adjusted in case of renal dysfunction. Recommended duration of therapy is 7 days but can be extended up to 14 days.

Intervention Type DRUG

Other Intervention Names

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Meronem® (meropenem) Meronem® (meropenem) Avalox® (moxifloxacin)

Eligibility Criteria

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Inclusion Criteria

* Severe sepsis or septic shock according to ACCP/SCCM criteria
* Onset of severe sepsis or septic shock \<24 h
* Informed consent
* Effective contraception in fertile women

Exclusion Criteria

* Age \<18 years
* Pregnancy
* Breast-feeding women
* Pretreatment with meropenem, imipenem, or ertapenem within the last 4 weeks (\>1 daily dosage)
* Pretreatment with moxifloxacin,ciprofloxacin, or levofloxacin within the last 4 weeks (\>1 daily dosage)
* Pretreatment with a pseudomonas effective cephalosporin (cefepime, ceftazidim, cefpirom) or piperacillin within the last 48 hours (\>1 daily dosage).
* Pretreatment with other chinolones within the last 4 weeks (\>1 daily dosage)
* Presence of infection where guidelines recommend another antimicrobial therapy than the study medication (i.e. endocarditis)
* Evidence or strong clinical suspicion of a microorganism where the study medication is known to be ineffective (i.e. tuberculosis, MRSA- or VRE-infection)
* Known allergy against meropenem or moxifloxacin
* Tendon disease or injury due to past quinolone therapy
* Congenital or acquired prolongation of QT-interval
* Concomitant medication which prolongs the QT-interval
* Electrolyte imbalance, especially uncorrected hypokalemia
* Clinically relevant bradycardia
* Clinically relevant cardiac dysfunction with reduced left-ventricular ejection fraction
* Symptomatic arrhythmias in the medical history
* Significant hepatic impairment (Child-Pugh C) or elevation of liver enzymes \>5x the upper normal range
* No commitment to full patient support (i.e. DNR order)
* Patient's death is considered imminent due to coexisting disease
* Concomitant participation in another study or study participation with in the last 30 days.
* Relationship of the patient to study team member (i.e. colleague, relative)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role collaborator

Kompetenznetz Sepsis

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Konrad Reinhart, MD

Role: STUDY_CHAIR

University Hospital Jena; Dep. of Anesthesiology and Intensive Care Medicine

Markus Löffler, MD

Role: STUDY_DIRECTOR

University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL)

Thomas Deufel, MD

Role: STUDY_DIRECTOR

University Hopitel Jena, Institute for Medical Chemistry

Locations

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University Hospital Aachen - Dep. of Anesthesiology

Aachen, , Germany

Site Status

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine

Augsburg, , Germany

Site Status

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine

Berlin, , Germany

Site Status

Charité Berlin - Dep. of Medicine (Cardiology, Angiology, Pneumology)

Berlin, , Germany

Site Status

Charité Campus Mitte -Dep.of Infectiology and Pneumonology

Berlin, , Germany

Site Status

Charité Campus Benjamin Franklin - Dep. of Medicine IV

Berlin, , Germany

Site Status

Vivantes Klinikum Neukölln - Cardiology

Berlin, , Germany

Site Status

Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy

Berlin, , Germany

Site Status

Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology

Berlin, , Germany

Site Status

Ev. Krankenhaus Gilead I - Dep. of Anesthesiology and Intensive Care Medicine

Bielefeld, , Germany

Site Status

University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine

Bonn, , Germany

Site Status

Städtisches Klinikum Brandenburg - Intensive Care Unit

Brandenburg, , Germany

Site Status

University Hospital Köln - Dep. of Internal Medicine I

Cologne, , Germany

Site Status

Hospital Merheim - Dep. of Anesthesiology and Intensive Care Medicine

Cologne, , Germany

Site Status

Klinikum Darmstadt - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy

Darmstadt, , Germany

Site Status

Klinikum Dessau - Dep. of Medicine

Dessau, , Germany

Site Status

Hospital Lippe-Detmold - Dep. of Anesthesiology and Intensive Care Medicine

Detmold, , Germany

Site Status

Krankenhaus Dresden-Friedrichstadt

Dresden, , Germany

Site Status

University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.

Dresden, , Germany

Site Status

HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine

Erfurt, , Germany

Site Status

University Erlangen-Nürnberg - Dep. of Medicine IV

Erlangen, , Germany

Site Status

University Hospital Freiburg - Dep. of Medicine III

Freiburg im Breisgau, , Germany

Site Status

Klinik am Eichert - Dep. of Anesthesiology, Intensive Care Medicine, and Pain Therapy

Göppingen, , Germany

Site Status

Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine

Göttingen, , Germany

Site Status

Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine

Greifswald, , Germany

Site Status

Ernst-Moritz-Arndt-Universität Greifswald, Dep. of Internal Medicine B

Greifswald, , Germany

Site Status

Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology and Intensive Care Medicine

Halle, , Germany

Site Status

Hospital Martha-Maria Halle-Dölau gGmbH - Dep. of Anesthesiology and Intensive Care Medicine

Halle, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine

Hamburg, , Germany

Site Status

Klinikum Hannover Nordstadt - Dep. of Anesthesiology and Intensive Care Medicine

Hanover, , Germany

Site Status

Medizinische Hochschule Hannover, Dep. of Internal Medicine/ Pneumology

Hanover, , Germany

Site Status

Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine

Heide, , Germany

Site Status

University Hospital Heidelberg - Dep. of Medicine IV

Heidelberg, , Germany

Site Status

University Hospital Heidelberg - Dep. of Visceral and Transplantation Surgery

Heidelberg, , Germany

Site Status

University Hospital Saarland - Deop. of Anesthesiology, Intensive Care Medicine, and Pain Therapy

Homburg/Saar, , Germany

Site Status

University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine

Jena, , Germany

Site Status

University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine

Kiel, , Germany

Site Status

University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine

Leipzig, , Germany

Site Status

Hospital Ludwigshafen am Rhein - Dep. of Cardiac Surgery

Ludwigshafen, , Germany

Site Status

Klinikum Lüdenscheid - Dep. of Anesthesiology

Lüdenscheid, , Germany

Site Status

University Hospital Mannheim - Dep. of Medicine I

Mannheim, , Germany

Site Status

University Hospital Munich - Dep. of Internal Medicine

Munich, , Germany

Site Status

Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention

Munich, , Germany

Site Status

Klinikum rechts der Isar - Dep. of Anesthesiology

Munich, , Germany

Site Status

University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine

Münster, , Germany

Site Status

Klinikum Oldenburg - Dep. of Anesthesiology, Intensive Care Medicine, Emergency Medicine, Pain Therapy

Oldenburg, , Germany

Site Status

Klinikum Ernst von Bergmann - Dep. of Anesthesiology and Intensive Care Medicine

Potsdam, , Germany

Site Status

University Hospital Rostock - Dep. of Anesthesiology and Intensive Care Medicine

Rostock, , Germany

Site Status

Ev. Jung-Stilling-Krankenhaus - Dep. of Anesthesiology, Intensive Care Medicine, Emergency Medicine

Siegen, , Germany

Site Status

University Hospital Tübingen - Dep. of Medicine

Tübingen, , Germany

Site Status

University Hospital Ulm - Dep. of Internal Medicine II

Ulm, , Germany

Site Status

Stiftung Juliusspital Würzburg - Dep. of Medicine (Cardiology)

Würzburg, , Germany

Site Status

Countries

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Germany

References

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American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74.

Reference Type BACKGROUND
PMID: 1597042 (View on PubMed)

Reinhart K, Brunkhorst F, Bone H, Gerlach H, Grundling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Werdan K; Deutsche Sepsis-Gesellschaft e.V. [Diagnosis and therapy of sepsis: guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. Anaesthesist. 2006 Jun;55 Suppl 1:43-56. German.

Reference Type BACKGROUND
PMID: 17051663 (View on PubMed)

Bochud PY, Bonten M, Marchetti O, Calandra T. Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review. Crit Care Med. 2004 Nov;32(11 Suppl):S495-512. doi: 10.1097/01.ccm.0000143118.41100.14.

Reference Type BACKGROUND
PMID: 15542958 (View on PubMed)

Harbarth S, Garbino J, Pugin J, Romand JA, Lew D, Pittet D. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med. 2003 Nov;115(7):529-35. doi: 10.1016/j.amjmed.2003.07.005.

Reference Type BACKGROUND
PMID: 14599631 (View on PubMed)

Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis. 2004 Aug;4(8):519-27. doi: 10.1016/S1473-3099(04)01108-9.

Reference Type BACKGROUND
PMID: 15288826 (View on PubMed)

Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, Gruendling M, Huhle G, Jaschinski U, John S, Mayer K, Oppert M, Olthoff D, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Bogatsch H, Hartog C, Loeffler M, Reinhart K. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med. 2007 Apr;33(4):606-18. doi: 10.1007/s00134-006-0517-7. Epub 2007 Feb 24.

Reference Type BACKGROUND
PMID: 17323051 (View on PubMed)

Pletz MW, Bloos F, Burkhardt O, Brunkhorst FM, Bode-Boger SM, Martens-Lobenhoffer J, Greer MW, Stass H, Welte T. Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock. Intensive Care Med. 2010 Jun;36(6):979-83. doi: 10.1007/s00134-010-1864-y. Epub 2010 Mar 25.

Reference Type BACKGROUND
PMID: 20336279 (View on PubMed)

Brunkhorst FM, Oppert M, Marx G, Bloos F, Ludewig K, Putensen C, Nierhaus A, Jaschinski U, Meier-Hellmann A, Weyland A, Grundling M, Moerer O, Riessen R, Seibel A, Ragaller M, Buchler MW, John S, Bach F, Spies C, Reill L, Fritz H, Kiehntopf M, Kuhnt E, Bogatsch H, Engel C, Loeffler M, Kollef MH, Reinhart K, Welte T; German Study Group Competence Network Sepsis (SepNet). Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA. 2012 Jun 13;307(22):2390-9. doi: 10.1001/jama.2012.5833.

Reference Type RESULT
PMID: 22692171 (View on PubMed)

Related Links

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Other Identifiers

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bmbf grant: 01 KI 01 06

Identifier Type: -

Identifier Source: secondary_id

EudraCT 2006-006984-21

Identifier Type: -

Identifier Source: org_study_id