The OPTIMAL TDM Study: Determining Optimal Beta-lactam Plasma Concentrations Through Therapeutic Drug Monitoring
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 771
- 试验地点
- 1
- 主要终点
- Incidence of clinical toxicity through day 30 after start of study antibiotic
研究概览
简要总结
Little is known of beta-lactam antibiotics' true therapeutic plasma concentration range. The aims of this study are to define evidence-based, safe and effective upper and lower limits of the plasma concentrations of imipenem, meropenem, amoxicillin, flucloxacillin, piperacillin, ceftazidime and cefepime in patients at increased risk of serious bacterial infections and currently understudied pharmacokinetics (the critically ill, the elderly, and the immunosuppressed).
This prospective observational study will include adult patients with suspected or confirmed systemic bacterial infection receiving one of the above-named antibiotics and hospitalized in intensive-care, step-down, or hematology-oncology units of the Geneva University Hospitals (HUG).
Eligible patients will be identified via the electronic health record (EHR). Patients receiving traditional intermittent dosing or prolonged infusions will undergo TDM for at least one intermediate (mid-interval) and one trough level at 24 hours (-12 or +48 hours) after the therapy's start. Patients receiving continuous infusions will undergo TDM for at least one steady-state level. Clinical course will be observed for 30 days from the start of the study antibiotic (1st day of study antibiotic =day 1).
The primary outcome is incidence of clinical toxicity through day 30 after start of study antibiotic (as stratified by BL trough concentration). Secondary outcomes are listed below.
详细描述
Little is known of beta-lactam antibiotics' true therapeutic plasma concentration range. The aims of this study are to define evidence-based, safe and effective upper and lower limits of the plasma concentrations of imipenem, meropenem, amoxicillin, flucloxacillin, piperacillin, ceftazidime and cefepime in patients at increased risk of serious bacterial infections and currently understudied pharmacokinetics (the critically ill, the elderly, and the immunosuppressed).
This prospective observational study will include adult patients with suspected or confirmed systemic bacterial infection receiving one of the above-named antibiotics and hospitalized in intensive-care, step-down, or hematology-oncology units of the Geneva University Hospitals (HUG).
Eligible patients will be identified via the electronic health record (EHR). Patients receiving traditional intermittent dosing or prolonged infusions will undergo TDM for at least one intermediate (mid-interval) and one trough level at 24 hours (-12 or +48 hours) after the therapy's start. Patients receiving continuous infusions will undergo TDM for at least one steady-state level. Clinical course will be observed for 30 days from the start of the study antibiotic (1st day of study antibiotic =day 1).
The primary outcome is incidence of clinical toxicity through day 30 after start of study antibiotic (as stratified by BL trough concentration). Secondary outcomes are listed below.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Hospitalized patients with suspected or confirmed systemic bacterial infection:
- •Receiving either imipenem-cilastatin, meropenem, amoxicillin (±clavulanic acid), flucloxacillin, piperacillin-tazobactam, ceftazidime or cefepime
- •Aged ≥18 years
- •Requiring intensive or intermediate-intensive (step-down) care OR severely immunosuppressed (see definitions)
排除标准
- •Planned imminent transfer to an outside hospital
- •Poor prognosis with life expectancy <1 week and/or intended transition to palliative care
结局指标
主要结局
Incidence of clinical toxicity through day 30 after start of study antibiotic
时间窗: day 30 after start of antibiotic
Incidence of clinical toxicity through day 30 after start of study antibiotic (as stratified by BL trough concentration)
次要结局
- The correlation of free versus total flucloxacillin concentrations(day 30)
- Incidence of clinical toxicity of piperacillin-tazobactam when co-administered with vancomycin(day 30)
- Incidence of emergence of resistance(day 30)
- Median intermediate and trough plasma concentrations of tazobactam(through day 30)
- clinical response in patients with neutropenic fever: incidence of clinical cure in this subpopulation(day 30)
- 30-day mortality attributable to the treated infection(day 30)
- 30-day all-cause mortality(day 30)
- incidence of reversible toxicity(day 30)
- Clinical response: incidence of clinical cure(day 30)
- Incidence of Clostridium difficile infection(day 30)
- Incidence of undetectable beta-lactam plasma concentrations(day 30)
- Incidence of off-label prescribing(day 30)
- Beta-lactam trough concentration/minimal inhibitory concentration (MIC) index(day 1 (±1))
研究者
Angela HUTTNER
Principal Investigator
University of Geneva, Switzerland