Septic Shock, Severe Sepsis
Conditions
Keywords
sepsis, antibiotics, carbapenems, fluoroquinolones, Severe sepsis and septic shock
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.
Interventions
DRUGmeropenem
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.
DRUGmeropenem, 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.
Sponsors
AstraZeneca
Bayer
Kompetenznetz Sepsis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean total SOFA score | study duration but not longer than 14 days |
Secondary
| Measure | Time frame |
|---|---|
| Antibiotics free days | 28 and 90 days |
| Costs of antibiotic therapy | ICU stay |
| Frequency of resistances to antibiotics | ICU stay |
| Frequency of new infections | — |
| Mortality | 28 and 90 days |
| ICU and hospital length of stay | — |
| SOFA-subscores | — |
| 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 |
| Response to therapy | day 7 and day 10 |
Countries
Germany
Outcome results
None listed