Not for Profit, Monocentric, Open Label Trial of Lorazepam, Randomized to Three Different Sequences of Boli and Continuous Infusion, for Sedation of Children Aged ≥1 and <12 Years Admitted in Intensive Care and Mechanically Ventilated.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 9
- 主要终点
- Lorazepam Pharmacokinetics (AUC)
研究概览
简要总结
The aim of this study is to better define the pharmacokinetic and pharmacodynamic profile of lorazepam for the analgosedation in pediatric intensive care unit. This will help to better define the dosages and administration modalities (bolus or continue infusion) required to achieve analgosedation with lorazepam in pediatric patients undergoing mechanical ventilation.
详细描述
The prolonged use of certain sedative drugs such as midazolam, whose metabolism is associated with the production of active metabolites, can lead to difficult management of sedative therapy and ventilatory weaning. The active metabolites, whose production is variable, determine in fact a difficulty in establishing a precision therapy, thus making it necessary to identify new molecules for sedation in pediatric intensive care unit (PICU). Lorazepam (LZ) is a benzodiazepine with an intermediate duration of activity, administered by continuous infusion or intermittent bolus, which has the advantages of higher potency compared to other benzodiazepines, a low cost and a metabolism that does not produce active metabolites. However, the presence of propylene glycol (PG), an excipient present in intravenous LZ formulations, although generally well tolerated, is potentially associated with episodes of tissue toxicity due to accumulation phenomena; this may represent a risk in cases where LZ is administered in high doses. This study, based on pharmacokinetic models obtained from data already available in the scientific literature, aims to define the pharmacokinetic and pharmacodynamic characteristics of LZ for the analgosedation of pediatric patients admitted to intensive care and subjected to mechanical ventilation. Preliminary evaluation of sedative efficacy will be carried out through COMFORT-B scale assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed written consent of the parents or legal representatives of minors according to national law;
- •Male and/or female subjects of the following ages: ≥1 year - <12 years;
- •Critical patients who need to undergo mechanical ventilation and hospitalized in PICU;
排除标准
- •Hospitalization in PICU expected to be less than 48 hours long;
- •Altered renal function (eGFR according to Schwartz < 30 mL/min/1.73 m2 or creatininemia > 2 vn);
- •Altered liver function (bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2 NU);
- •Altered cardiac function (Ejection Fraction < 50%);
- •Need for administration of neuromuscular blocking drugs;
- •Concomitant therapy with continuous infusion drugs containing PG;
- •Metronidazole therapy in the three months prior to enrollment;
- •History of exposure to LZ in the seven days prior to enrollment;
- •Participation in other experimental clinical trials;
- •Patient undergoing extracorporeal circulation (dialysis, ECMO)
- •Known allergic reaction to LZ or its excipients;
- •Weight < 9 kg;
- •Known immaturity of the enzymatic system of alcohol dehydrogenase;
- •Pregnancy in progress;
- •Ingestion of antifreeze;
- •Treatment with silver sulfadiazine for wound care;
- •Oncological pathology diagnosed or suspected;
- •Valproic acid therapy
- •Patients undergoing continuous infusion therapy with drugs used for sedation prior to admission to the red area (excluding dexmedetomidine).
研究组 & 干预措施
Sequence 1
The subjects enrolled in this arm, will undergo the following lorazepam administration scheme:
- Day 1: 6 Boluses at 0.1 mg/kg LZ every 4 hours
- Day 2: 6 Boluses at 0.2 mg/kg LZ every 4 hours
- Day 3: Continuous Infusion at 0.025 mg/kg/hour LZ
干预措施: Lorazepam 4 mg/ml (Drug)
Sequence 2
The subjects enrolled in this arm, will undergo the following lorazepam administration scheme:
- Day 1: 6 Boluses at 0.2 mg/kg LZ every 4 hours
- Day 2: 6 Boluses at 0.1 mg/kg LZ every 4 hours
- Day 3: Continuous Infusion at 0.03 mg/kg/hour LZ
干预措施: Lorazepam 4 mg/ml (Drug)
Sequence 3
The subjects enrolled in this arm, will undergo the following lorazepam administration scheme:
- Day 1: 6 Boluses at 0.3 mg/kg LZ every 4 hours
- Day 2: 6 Boluses at 0.1 mg/kg LZ every 4 hours
- Day 3: Continuous Infusion at 0.025 mg/kg/hour LZ
干预措施: Lorazepam 4 mg/ml (Drug)
结局指标
主要结局
Lorazepam Pharmacokinetics (AUC)
时间窗: 72 hours from enrollment
AUC of Lorazepam
次要结局
- Dropouts due to any adverse event(72 hours from enrollment)
- Adverse Events (AEs)/ Serious Adverse Events (SAEs) registration at end of study(72 hours from enrollment)
- Vital signs at the end of study (Body Temperature)(72 hours from enrollment)
- Osmol gap at the end of study(72 hours from enrollment)
- Kidney Function at the end of study(72 hours from enrollment)
- AEs/SAEs registration at end of follow-up(6 days from enrollment)
- Vital signs at the end of study (Blood Pressure)(72 hours from enrollment)
- Vital signs at the end of follow-up (Heart Rate)(6 days from enrollment)
- N-GAL at the end of study(72 hours from enrollment)
- Lorazepam Pharmacokinetics (Cmax)(72 hours from enrollment)
- COMFORT-BEHAVIOURAL (COMFORT-B) scale(72 hours from enrollment)
- Vital signs at the end of study (Heart Rate)(72 hours from enrollment)
- Vital signs at the end of follow-up (Body Temperature)(6 days from enrollment)
- Plasma concentrations of Propylene Glycol at the end of study(72 hours from enrollment)
- C-Cystatin at the end of study(72 hours from enrollment)
- Lorazepam Pharmacokinetics (Drug Clearance)(72 hours from enrollment)
- Lorazepam Pharmacokinetics (Cmin)(72 hours from enrollment)
- Analgosedative efficacy of Lorazepam(72 hours from enrollment)
- Vital signs at the end of follow-up (Blood Pressure)(6 days from enrollment)
- Lorazepam Pharmacokinetics (Tmax)(72 hours from enrollment)
- Lorazepam Pharmacokinetics (Half Life)(72 hours from enrollment)
研究者
Marco Marano
Principal Investigator
Bambino Gesù Hospital and Research Institute