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
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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: 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 ]

Enrollment: 600
Study Start Date: October 2007
Study Completion Date: June 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MeroMono
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.
Other Name: Meronem® (meropenem)
Active Comparator: MeroMoxi
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.
Other Names:
  • Meronem® (meropenem)
  • Avalox® (moxifloxacin)

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

  Show 52 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:
Publications:

Responsible Party: Kompetenznetz Sepsis
ClinicalTrials.gov Identifier: NCT00534287     History of Changes
Other Study ID Numbers: EudraCT 2006-006984-21, bmbf grant: 01 KI 01 06
Study First Received: September 21, 2007
Last Updated: June 28, 2012
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:
Sepsis
Toxemia
Shock
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Anti-Bacterial Agents
Meropenem
Antibiotics, Antitubercular
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014