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

Kompetenznetz Sepsis

Status and phase

Completed

Phase 3

Conditions

Severe Sepsis

Septic Shock

Treatments

Drug: meropenem, moxifloxacin

Drug: meropenem

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00534287

bmbf grant: 01 KI 01 06

EudraCT 2006-006984-21

Details and patient eligibility

About

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.

Full 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.

Enrollment

600 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)