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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 600
- 试验地点
- 52
- 主要终点
- Mean total SOFA score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
MeroMono
Monotherapy with meropenem
干预措施: meropenem (Drug)
MeroMoxi
Combination therapy with meropenem + moxifloxacin
干预措施: meropenem, moxifloxacin (Drug)
结局指标
主要结局
Mean total SOFA score
时间窗: study duration but not longer than 14 days
次要结局
- 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