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
Overview
- Phase
- Phase 3
- Intervention
- meropenem
- Conditions
- Severe Sepsis
- Sponsor
- Kompetenznetz Sepsis
- Enrollment
- 600
- Locations
- 52
- Primary Endpoint
- Mean total SOFA score
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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.
Investigators
Eligibility 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
Arms & Interventions
MeroMono
Monotherapy with meropenem
Intervention: meropenem
MeroMoxi
Combination therapy with meropenem + moxifloxacin
Intervention: meropenem, moxifloxacin
Outcomes
Primary Outcomes
Mean total SOFA score
Time Frame: study duration but not longer than 14 days
Secondary Outcomes
- Ventilator free days(28 and 90 days)
- 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)
- 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