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

NCT00534287 | Completed Phase 3 DMC

• 2 other identifiers: EudraCT 2006-006984-21bmbf grant: 01 KI 01 06
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 52

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.

Conditions

Severe Sepsis; Septic Shock

Keywords

sepsis; antibiotics; carbapenems; fluoroquinolones; Severe sepsis and septic shock

Outcome Measures

Primary Outcomes (1)

• Mean total SOFA score

  study duration but not longer than 14 days

Secondary Outcomes (13)

• Mortality

  28 and 90 days

• ICU and hospital length of stay

• Response to therapy

  day 7 and day 10

• Clinical and microbiological cure

  End of study therapy (day 7-14) and release from ICU (max. day 21)

• Frequency of adverse events (AEs, SAEs, SUSARs)

Study Arms (2)

MeroMono

ACTIVE COMPARATOR

Monotherapy with meropenem

Drug: meropenem

MeroMoxi

ACTIVE COMPARATOR

Combination therapy with meropenem + moxifloxacin

Drug: meropenem, moxifloxacin

Interventions

meropenem 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.

Also known as: Meronem® (meropenem)

MeroMono

meropenem, moxifloxacin 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.

Also known as: Meronem® (meropenem), Avalox® (moxifloxacin)

MeroMoxi

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kompetenznetz Sepsis: lead
• AstraZeneca: collaborator
• Bayer: collaborator

Study Sites (52)

University Hospital Aachen - Dep. of Anesthesiology

Aachen, 52074, Germany

Location

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine

Augsburg, 86156, Germany

Location

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine

Berlin, 10117, Germany

Location

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

Berlin, 10117, Germany

Location

Charité Campus Mitte -Dep.of Infectiology and Pneumonology

Berlin, 10117, Germany

Location

Charité Campus Benjamin Franklin - Dep. of Medicine IV

Berlin, 12203, Germany

Location

Vivantes Klinikum Neukölln - Cardiology

Berlin, 12313, Germany

Location

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

Berlin, 12313, Germany

Location

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

Berlin, 13353, Germany

Location

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

Bielefeld, 33617, Germany

Location

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

Bonn, 53105, Germany

Location

Städtisches Klinikum Brandenburg - Intensive Care Unit

Brandenburg, 14770, Germany

Location

University Hospital Köln - Dep. of Internal Medicine I

Cologne, 50924, Germany

Location

Hospital Merheim - Dep. of Anesthesiology and Intensive Care Medicine

Cologne, 51109, Germany

Location

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

Darmstadt, 64283, Germany

Location

Klinikum Dessau - Dep. of Medicine

Dessau, 06847, Germany

Location

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

Detmold, 32756, Germany

Location

Krankenhaus Dresden-Friedrichstadt

Dresden, 01067, Germany

Location

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

Dresden, 01307, Germany

Location

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

Erfurt, 99089, Germany

Location

University Erlangen-Nürnberg - Dep. of Medicine IV

Erlangen, 91054, Germany

Location

University Hospital Freiburg - Dep. of Medicine III

Freiburg im Breisgau, 79106, Germany

Location

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

Göppingen, 73035, Germany

Location

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

Göttingen, 37075, Germany

Location

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

Greifswald, 17475, Germany

Location

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

Greifswald, 17475, Germany

Location

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

Halle, 06097, Germany

Location

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

Halle, 06120, Germany

Location

Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine

Hamburg, 20246, Germany

Location

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

Hanover, 30167, Germany

Location

Medizinische Hochschule Hannover, Dep. of Internal Medicine/ Pneumology

Hanover, 30625, Germany

Location

Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine

Heide, 25746, Germany

Location

University Hospital Heidelberg - Dep. of Medicine IV

Heidelberg, 69120, Germany

Location

University Hospital Heidelberg - Dep. of Visceral and Transplantation Surgery

Heidelberg, 69120, Germany

Location

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

Homburg/Saar, 66421, Germany

Location

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

Jena, 07747, Germany

Location

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

Kiel, 24105, Germany

Location

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

Leipzig, 04103, Germany

Location

Hospital Ludwigshafen am Rhein - Dep. of Cardiac Surgery

Ludwigshafen, 67063, Germany

Location

Klinikum Lüdenscheid - Dep. of Anesthesiology

Lüdenscheid, 58515, Germany

Location

University Hospital Mannheim - Dep. of Medicine I

Mannheim, 68167, Germany

Location

University Hospital Munich - Dep. of Internal Medicine

Munich, 80336, Germany

Location

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

Munich, 81545, Germany

Location

Klinikum rechts der Isar - Dep. of Anesthesiology

Munich, 81675, Germany

Location

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

Münster, 48149, Germany

Location

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

Oldenburg, 26133, Germany

Location

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

Potsdam, 14467, Germany

Location

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

Rostock, 18057, Germany

Location

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

Siegen, 57074, Germany

Location

University Hospital Tübingen - Dep. of Medicine

Tübingen, 72076, Germany

Location

University Hospital Ulm - Dep. of Internal Medicine II

Ulm, 89081, Germany

Location

Stiftung Juliusspital Würzburg - Dep. of Medicine (Cardiology)

Würzburg, 97070, Germany

Location

Related Publications (8)

• 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.

  PMID: 1597042 BACKGROUND

• 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.

  PMID: 17051663 BACKGROUND

• 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.

  PMID: 15542958 BACKGROUND

• 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.

  PMID: 14599631 BACKGROUND

• 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.

  PMID: 15288826 BACKGROUND

• 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.

  PMID: 17323051 BACKGROUND

• 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.

  PMID: 20336279 BACKGROUND

• 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.

  PMID: 22692171 RESULT

Related Links

• Competence Network Sepsis (SepNet)
• German Sepsis Society

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Meropenem; Moxifloxacin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Konrad Reinhart, MD

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

  STUDY CHAIR

• Markus Löffler, MD

  University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL)

  STUDY DIRECTOR

• Thomas Deufel, MD

  University Hopitel Jena, Institute for Medical Chemistry

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2007
• First Posted: September 24, 2007
• Study Start: October 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2010
• Last Updated: June 29, 2012

Record last verified: 2012-06

Locations

DE (52)