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

Phase 3

Completed

• Conditions: Severe Sepsis; Septic Shock
• Interventions: Drug: meropenem; Drug: meropenem, moxifloxacin

• Registration Number: NCT00534287
• Lead Sponsor: Kompetenznetz Sepsis

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2007-09-21
• Study First Submitted QC: 2007-09-21
• Study First Posted: 2007-09-24
• Study Start: 2007-10
• Primary Completion: 2010-04
• Study Completion: 2010-06
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-28
• Last Update Posted: 2012-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 600

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MeroMono	meropenem	Monotherapy with meropenem
MeroMoxi	meropenem, moxifloxacin	Combination therapy with meropenem + moxifloxacin

Primary Outcome Measures

Name	Time	Method
Mean total SOFA score	study duration but not longer than 14 days

Secondary Outcome Measures

Name	Time	Method
Mortality	28 and 90 days
ICU and hospital length of stay
Response to therapy	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

Trial Locations

Locations (52)

University Hospital Aachen - Dep. of Anesthesiology; 🇩🇪 Aachen, Germany

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine; 🇩🇪 Augsburg, Germany

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine; 🇩🇪 Berlin, Germany

Charité Berlin - Dep. of Medicine (Cardiology, Angiology, Pneumology); 🇩🇪 Berlin, Germany

Charité Campus Mitte -Dep.of Infectiology and Pneumonology; 🇩🇪 Berlin, Germany

Charité Campus Benjamin Franklin - Dep. of Medicine IV; 🇩🇪 Berlin, Germany

Vivantes Klinikum Neukölln - Cardiology; 🇩🇪 Berlin, Germany

Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy; 🇩🇪 Berlin, Germany

Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology; 🇩🇪 Berlin, Germany

Ev. Krankenhaus Gilead I - Dep. of Anesthesiology and Intensive Care Medicine; 🇩🇪 Bielefeld, Germany

Scroll for more (42 remaining)