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| ID | Type | Description | Link |
|---|---|---|---|
| bmbf grant: 01 KI 01 06 |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
| Bayer | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MeroMono | Active Comparator | Monotherapy with meropenem |
|
| MeroMoxi | Active Comparator | Combination therapy with meropenem + moxifloxacin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean total SOFA score | study duration but not longer than 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | 28 and 90 days | |
| ICU and hospital length of stay | ||
| Response to therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Aachen - Dep. of Anesthesiology | Aachen | 52074 | Germany | |||
| Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1597042 | Background | 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. | |
| 17051663 | 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. |
| Label | URL |
|---|---|
| Competence Network Sepsis (SepNet) | View source |
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|
| 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. |
|
|
| 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) |
| Ventilator free days | 28 and 90 days |
| Days without renal replacement therapy | 28 and 90 days |
| Vasopressor free days | 28 and 90 days |
| SOFA-subscores |
| Antibiotics free days | 28 and 90 days |
| Costs of antibiotic therapy | ICU stay |
| Frequency of resistances to antibiotics | ICU stay |
| Frequency of new infections |
| Augsburg |
| 86156 |
| 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 Mitte -Dep.of Infectiology and Pneumonology | Berlin | 10117 | Germany |
| Charité Campus Benjamin Franklin - Dep. of Medicine IV | Berlin | 12203 | Germany |
| Vivantes Klinikum Neukölln - Cardiology | Berlin | 12313 | Germany |
| Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy | Berlin | 12313 | Germany |
| Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology | Berlin | 13353 | 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 |
| University Hospital Köln - Dep. of Internal Medicine I | Cologne | 50924 | Germany |
| Hospital Merheim - Dep. of Anesthesiology and Intensive Care Medicine | Cologne | 51109 | 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 im Breisgau | 79106 | 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 |
| 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 |
| Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology and Intensive Care Medicine | Halle | 06097 | Germany |
| Hospital Martha-Maria Halle-Dölau gGmbH - Dep. of Anesthesiology and Intensive Care Medicine | Halle | 06120 | Germany |
| Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine | Hamburg | 20246 | Germany |
| Klinikum Hannover Nordstadt - Dep. of Anesthesiology and Intensive Care Medicine | Hanover | 30167 | Germany |
| Medizinische Hochschule Hannover, Dep. of Internal Medicine/ Pneumology | Hanover | 30625 | Germany |
| Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine | Heide | 25746 | Germany |
| University Hospital Heidelberg - Dep. of Medicine IV | Heidelberg | 69120 | Germany |
| University Hospital Heidelberg - Dep. of Visceral and Transplantation Surgery | Heidelberg | 69120 | 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 |
| 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 | Lüdenscheid | 58515 | Germany |
| University Hospital Mannheim - Dep. of Medicine I | Mannheim | 68167 | Germany |
| University Hospital Munich - Dep. of Internal Medicine | Munich | 80336 | 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 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 |
| 15542958 | 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. |
| 14599631 | 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. |
| 15288826 | 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. |
| 17323051 | 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. |
| 20336279 | 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. |
| 22692171 | Result | 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. |
| German Sepsis Society | View source |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D000077731 | Meropenem |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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