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

Phase 3
Completed
Conditions
Severe Sepsis
Septic Shock
Interventions
Registration Number
NCT00534287
Lead Sponsor
Kompetenznetz Sepsis
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
600
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MeroMonomeropenemMonotherapy with meropenem
MeroMoximeropenem, moxifloxacinCombination therapy with meropenem + moxifloxacin
Primary Outcome Measures
NameTimeMethod
Mean total SOFA scorestudy duration but not longer than 14 days
Secondary Outcome Measures
NameTimeMethod
Mortality28 and 90 days
ICU and hospital length of stay
Response to therapyday 7 and day 10
Clinical and microbiological cureEnd of study therapy (day 7-14) and release from ICU (max. day 21)
Frequency of adverse events (AEs, SAEs, SUSARs)
Ventilator free days28 and 90 days
Days without renal replacement therapy28 and 90 days
Vasopressor free days28 and 90 days
SOFA-subscores
Antibiotics free days28 and 90 days
Costs of antibiotic therapyICU stay
Frequency of resistances to antibioticsICU stay
Frequency of new infections

Trial Locations

Locations (52)

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

🇩🇪

Oldenburg, Germany

University Hospital Ulm - Dep. of Internal Medicine II

🇩🇪

Ulm, Germany

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

🇩🇪

Münster, Germany

University Hospital Mannheim - Dep. of Medicine I

🇩🇪

Mannheim, Germany

University Hospital Munich - Dep. of Internal Medicine

🇩🇪

Munich, Germany

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

🇩🇪

Munich, Germany

Klinikum rechts der Isar - Dep. of Anesthesiology

🇩🇪

Munich, Germany

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

🇩🇪

Potsdam, Germany

University Hospital Tübingen - Dep. of Medicine

🇩🇪

Tübingen, Germany

Stiftung Juliusspital Würzburg - Dep. of Medicine (Cardiology)

🇩🇪

Würzburg, Germany

University Hospital Aachen - Dep. of Anesthesiology

🇩🇪

Aachen, Germany

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine

🇩🇪

Augsburg, Germany

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine

🇩🇪

Berlin, Germany

Charité Campus Benjamin Franklin - Dep. of Medicine IV

🇩🇪

Berlin, Germany

Charité Campus Mitte -Dep.of Infectiology and Pneumonology

🇩🇪

Berlin, Germany

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

🇩🇪

Berlin, Germany

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

🇩🇪

Berlin, Germany

Vivantes Klinikum Neukölln - Cardiology

🇩🇪

Berlin, Germany

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

🇩🇪

Bonn, Germany

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

🇩🇪

Berlin, Germany

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

🇩🇪

Bielefeld, Germany

Städtisches Klinikum Brandenburg - Intensive Care Unit

🇩🇪

Brandenburg, Germany

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

🇩🇪

Darmstadt, Germany

Klinikum Dessau - Dep. of Medicine

🇩🇪

Dessau, Germany

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

🇩🇪

Detmold, Germany

Krankenhaus Dresden-Friedrichstadt

🇩🇪

Dresden, Germany

University Erlangen-Nürnberg - Dep. of Medicine IV

🇩🇪

Erlangen, Germany

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

🇩🇪

Dresden, Germany

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

🇩🇪

Erfurt, Germany

University Hospital Freiburg - Dep. of Medicine III

🇩🇪

Freiburg, Germany

Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine

🇩🇪

Hamburg, Germany

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

🇩🇪

Greifswald, Germany

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

🇩🇪

Greifswald, Germany

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

🇩🇪

Göppingen, Germany

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

🇩🇪

Göttingen, Germany

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

🇩🇪

Halle, Germany

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

🇩🇪

Halle, Germany

University Hospital Heidelberg - Dep. of Medicine IV

🇩🇪

Heidelberg, Germany

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

🇩🇪

Homburg/Saar, Germany

Hospital Merheim - Dep. of Anesthesiology and Intensive Care Medicine

🇩🇪

Köln, Germany

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

🇩🇪

Hannover, Germany

Medizinische Hochschule Hannover, Dep. of Internal Medicine/ Pneumology

🇩🇪

Hannover, Germany

University Hospital Heidelberg - Dep. of Visceral and Transplantation Surgery

🇩🇪

Heidelberg, Germany

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

🇩🇪

Leipzig, Germany

Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine

🇩🇪

Heide, Germany

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

🇩🇪

Jena, Germany

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

🇩🇪

Kiel, Germany

University Hospital Köln - Dep. of Internal Medicine I

🇩🇪

Köln, Germany

Klinikum Lüdenscheid - Dep. of Anesthesiology

🇩🇪

Luedenscheid, Germany

Hospital Ludwigshafen am Rhein - Dep. of Cardiac Surgery

🇩🇪

Ludwigshafen, Germany

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

🇩🇪

Siegen, Germany

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

🇩🇪

Rostock, Germany

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