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

Information source: Kompetenznetz Sepsis
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Severe Sepsis; Septic Shock

Intervention: meropenem (Drug); meropenem, moxifloxacin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Kompetenznetz Sepsis

Official(s) and/or principal investigator(s):
Konrad Reinhart, MD, Study Chair, Affiliation: University Hospital Jena; Dep. of Anesthesiology and Intensive Care Medicine
Markus Löffler, MD, Study Director, Affiliation: University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL)
Thomas Deufel, MD, Study Director, Affiliation: University Hopitel Jena, Institute for Medical Chemistry

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.

Clinical Details

Official title: Prospective, Randomized, Open, Multicentre Study About the Effect of an Empirical Antibiotic Monotherapy With Meropenem (Meronem) Versus a Combination Therapy With Moxifloxacin (Avalox) on Organ Dysfunction in Patients With Severe Sepsis and Septic Shock

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mean total SOFA score

Secondary outcome:

Mortality

ICU and hospital length of stay

Response to therapy

Clinical and microbiological cure

Frequency of adverse events (AEs, SAEs, SUSARs)

Ventilator free days

Days without renal replacement therapy

Vasopressor free days

SOFA-subscores

Antibiotics free days

Costs of antibiotic therapy

Frequency of resistances to antibiotics

Frequency of new infections

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

Locations and Contacts

University Hospital Aachen - Dep. of Anesthesiology, Aachen 52074, Germany

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine, Augsburg 86156, Germany

Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology, Berlin 13353, Germany

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine, Berlin 10117, Germany

Charité Berlin - Dep. of Medicine (Cardiology, Angiology, Pneumology), Berlin 10117, Germany

Charité Campus Benjamin Franklin - Dep. of Medicine IV, Berlin 12203, Germany

Charité Campus Mitte -Dep.of Infectiology and Pneumonology, Berlin 10117, Germany

Vivantes Klinikum Neukölln - Cardiology, Berlin 12313, Germany

Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy, Berlin 12313, Germany

Ev. Krankenhaus Gilead I - Dep. of Anesthesiology and Intensive Care Medicine, Bielefeld 33617, Germany

University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine, Bonn 53105, Germany

Städtisches Klinikum Brandenburg - Intensive Care Unit, Brandenburg 14770, Germany

Klinikum Darmstadt - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy, Darmstadt 64283, Germany

Klinikum Dessau - Dep. of Medicine, Dessau 06847, Germany

Hospital Lippe-Detmold - Dep. of Anesthesiology and Intensive Care Medicine, Detmold 32756, Germany

Krankenhaus Dresden-Friedrichstadt, Dresden 01067, Germany

University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med., Dresden 01307, Germany

HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine, Erfurt 99089, Germany

University Erlangen-Nürnberg - Dep. of Medicine IV, Erlangen 91054, Germany

University Hospital Freiburg - Dep. of Medicine III, Freiburg 79106, Germany

Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine, Greifswald 17475, Germany

Ernst-Moritz-Arndt-Universität Greifswald, Dep. of Internal Medicine B, Greifswald 17475, Germany

Klinik am Eichert - Dep. of Anesthesiology, Intensive Care Medicine, and Pain Therapy, Göppingen 73035, Germany

Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine, Göttingen 37075, Germany

Hospital Martha-Maria Halle-Dölau gGmbH - Dep. of Anesthesiology and Intensive Care Medicine, Halle 06120, Germany

Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology and Intensive Care Medicine, Halle 06097, Germany

Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine, Hamburg 20246, Germany

Klinikum Hannover Nordstadt - Dep. of Anesthesiology and Intensive Care Medicine, Hannover 30167, Germany

Medizinische Hochschule Hannover, Dep. of Internal Medicine/ Pneumology, Hannover 30625, Germany

University Hospital Heidelberg - Dep. of Medicine IV, Heidelberg 69120, Germany

University Hospital Heidelberg - Dep. of Visceral and Transplantation Surgery, Heidelberg 69120, Germany

Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine, Heide 25746, Germany

University Hospital Saarland - Deop. of Anesthesiology, Intensive Care Medicine, and Pain Therapy, Homburg/Saar 66421, Germany

University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine, Jena 07747, Germany

University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine, Kiel 24105, Germany

Hospital Merheim - Dep. of Anesthesiology and Intensive Care Medicine, Köln 51109, Germany

University Hospital Köln - Dep. of Internal Medicine I, Köln 50924, Germany

University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine, Leipzig 04103, Germany

Hospital Ludwigshafen am Rhein - Dep. of Cardiac Surgery, Ludwigshafen 67063, Germany

Klinikum Lüdenscheid - Dep. of Anesthesiology, Luedenscheid 58515, Germany

University Hospital Mannheim - Dep. of Medicine I, Mannheim 68167, Germany

Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention, Munich 81545, Germany

Klinikum rechts der Isar - Dep. of Anesthesiology, Munich 81675, Germany

University Hospital Munich - Dep. of Internal Medicine, Munich 80336, Germany

University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine, Münster 48149, Germany

Klinikum Oldenburg - Dep. of Anesthesiology, Intensive Care Medicine, Emergency Medicine, Pain Therapy, Oldenburg 26133, Germany

Klinikum Ernst von Bergmann - Dep. of Anesthesiology and Intensive Care Medicine, Potsdam 14467, Germany

University Hospital Rostock - Dep. of Anesthesiology and Intensive Care Medicine, Rostock 18057, Germany

Ev. Jung-Stilling-Krankenhaus - Dep. of Anesthesiology, Intensive Care Medicine, Emergency Medicine, Siegen 57074, Germany

University Hospital Tübingen - Dep. of Medicine, Tübingen 72076, Germany

University Hospital Ulm - Dep. of Internal Medicine II, Ulm 89081, Germany

Stiftung Juliusspital Würzburg - Dep. of Medicine (Cardiology), Würzburg 97070, Germany

Additional Information

Competence Network Sepsis (SepNet)

German Sepsis Society

Related publications:

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. Review.

Reinhart K, Brunkhorst F, Bone H, Gerlach H, Gründling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Quintel M, Ragaller M, Rossaint R, Stüber 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. Review. German.

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. Review.

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.

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.

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. Epub 2007 Feb 24.

Pletz MW, Bloos F, Burkhardt O, Brunkhorst FM, Bode-Böger 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.

Starting date: October 2007
Last updated: June 28, 2012

Page last updated: August 23, 2015

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