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

Sponsor:	Kompetenznetz Sepsis
Collaborators:	AstraZeneca Bayer
Information provided by:	Kompetenznetz Sepsis
ClinicalTrials.gov Identifier:	NCT00534287

Purpose

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.

Condition	Intervention	Phase
Severe Sepsis Septic Shock	Drug: meropenem Drug: meropenem, moxifloxacin	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Sepsis

Drug Information available for: Meropenem Moxifloxacin Moxifloxacin hydrochloride

U.S. FDA Resources

Further study details as provided by Kompetenznetz Sepsis:

Primary Outcome Measures:

Mean total SOFA score [ Time Frame: study duration but not longer than 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mortality [ Time Frame: 80 and 90 days ] [ Designated as safety issue: No ]
ICU and hospital length of stay [ Designated as safety issue: No ]
Response to therapy [ Time Frame: day 7 and day 10 ] [ Designated as safety issue: No ]
Clinical and microbiological cure [ Time Frame: End of study therapy (day 7-14) and release from ICU (max. day 21) ] [ Designated as safety issue: No ]
Frequency of adverse events (AEs, SAEs, SUSARs) [ Designated as safety issue: Yes ]
Ventilator free days [ Time Frame: 28 and 90 days ] [ Designated as safety issue: No ]
Days without renal replacement therapy [ Time Frame: 28 and 90 days ] [ Designated as safety issue: No ]
Vasopressor free days [ Time Frame: 28 and 90 days ] [ Designated as safety issue: No ]
SOFA-subscores [ Designated as safety issue: No ]
Antibiotics free days [ Time Frame: 28 and 90 days ] [ Designated as safety issue: Yes ]
Costs of antibiotic therapy [ Time Frame: ICU stay ] [ Designated as safety issue: No ]
Frequency of resistances to antibiotics [ Time Frame: ICU stay ] [ Designated as safety issue: Yes ]
Frequency of new infections [ Designated as safety issue: Yes ]

Estimated Enrollment:	600
Study Start Date:	October 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
MeroMono: Active Comparator Monotherapy with meropenem	Drug: 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.
MeroMoxi: Active Comparator Combination therapy with meropenem + moxifloxacin	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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00534287

Contacts

Contact: Frank M. Brunkhorst, M.D.

+49-3641-9323383

Frank.Brunkhorst@med.uni-jena.de

Show 53 Study Locations

Sponsors and Collaborators

Kompetenznetz Sepsis

AstraZeneca

Bayer

Investigators

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

More Information

Additional Information:

Competence Networks in Medicine This link exits the ClinicalTrials.gov site

Competence Network Sepsis (SepNet) This link exits the ClinicalTrials.gov site

German Sepsis Society This link exits the ClinicalTrials.gov site

Publications:

[No authors listed] 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, 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. 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.

Study ID Numbers:	EudraCT 2006-006984-21, bmbf grant: 01 KI 01 06
Study First Received:	September 21, 2007
Last Updated:	November 25, 2009
ClinicalTrials.gov Identifier:	NCT00534287 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Kompetenznetz Sepsis:

sepsis
antibiotics
carbapenems
fluoroquinolones
Severe sepsis and septic shock

Additional relevant MeSH terms:

Systemic Inflammatory Response Syndrome
Anti-Infective Agents
Infection
Pharmacologic Actions
Inflammation
Anti-Bacterial Agents
Sepsis

Pathologic Processes
Shock
Moxifloxacin
Meropenem
Therapeutic Uses
Shock, Septic

ClinicalTrials.gov processed this record on February 08, 2010