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

This study has been completed.
Sponsor:
Collaborators:
AstraZeneca
Bayer
Information provided by (Responsible Party):
Kompetenznetz Sepsis
ClinicalTrials.gov Identifier:
NCT00534287
First received: September 21, 2007
Last updated: June 28, 2012
Last verified: June 2012

September 21, 2007
June 28, 2012
October 2007
April 2010   (final data collection date for primary outcome measure)
Mean total SOFA score [ Time Frame: study duration but not longer than 14 days ] [ Designated as safety issue: No ]
Mean total SOFA score [ Time Frame: study duration but not longer than 14 days ]
Complete list of historical versions of study NCT00534287 on ClinicalTrials.gov Archive Site
  • Mortality [ Time Frame: 28 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 ]
  • Mortality [ Time Frame: 80 and 90 days ]
  • ICU and hospital length of stay
  • Response to therapy [ Time Frame: day 7 and day 10 ]
  • Clinical and microbiological cure [ Time Frame: End of study therapy (day 7-14) and release from ICU (max. day 21) ]
  • Frequency of adverse events (AEs, SAEs, SUSARs)
  • Ventilator free days [ Time Frame: 28 and 90 days ]
  • Days without renal replacement therapy [ Time Frame: 28 and 90 days ]
  • Vasopressor free days [ Time Frame: 28 and 90 days ]
  • SOFA-subscores
  • Antibiotics free days [ Time Frame: 28 and 90 days ]
  • Costs of antibiotic therapy
  • Frequency of resistances to antibiotics
  • Frequency of new infections
Not Provided
Not Provided
 
Comparison of Two Antibiotic Regimen (Meropenem Versus Meropenem+Moxifloxacin)in the Treatment of Severe Sepsis and Septic Shock
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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Severe Sepsis
  • Septic Shock
  • 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.
    Other Name: Meronem® (meropenem)
  • 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.
    Other Names:
    • Meronem® (meropenem)
    • Avalox® (moxifloxacin)
  • Active Comparator: MeroMono
    Monotherapy with meropenem
    Intervention: Drug: meropenem
  • Active Comparator: MeroMoxi
    Combination therapy with meropenem + moxifloxacin
    Intervention: Drug: meropenem, moxifloxacin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
600
June 2010
April 2010   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00534287
EudraCT 2006-006984-21, bmbf grant: 01 KI 01 06
Yes
Kompetenznetz Sepsis
Kompetenznetz Sepsis
  • AstraZeneca
  • Bayer
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
Kompetenznetz Sepsis
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP