Dose Escalation Pharmacokinetic Study of Intranasal Atomized Dexmedetomidine in Pediatric Patients With Congenital Heart Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Time of Peak Drug Concentration Level of Dexmedetomidine
研究概览
简要总结
The main objectives of the study are to determine peak plasma drug concentration levels and corresponding time of dexmedetomidine following intranasal administration in children age ≥1 mo to ≤ 6 yr with congenital heart disease undergoing an elective diagnostic or interventional cardiac catheterization procedure.
详细描述
The high anxiety levels that children may experience during the preoperative period may be associated with negative medical, psychological, and social consequences. To reduce this stress, and to facilitate separation from parents and the induction of anesthesia, children are often given a sedative prior to undergoing a procedure. Dexmedetomidine is a highly selective a2-adrenergic receptor agonist with sedative, anxiolytic, and analgesic properties. While off-label in its use, the administration of dexmedetomidine by the intranasal route has become a popular and effective technique for sedation in children because it is non-invasive, easy to administer, well tolerated, and relatively fast in onset. Despite this, little consistent data have been published on its onset time, duration of action, or optimal dose. The only available pharmacokinetic (PK) data on dexmedetomidine in pediatric patients is in children who were administered IV dexmedetomidine. We are proposing a prospective open-label inter-subject cohort dose-escalation pharmacokinetic study to obtain peak dexmedetomidine drug concentration level in plasma and the corresponding time point following intranasal administration in the pediatric patient with cardiac disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects age ≥1 mo to ≤6 yo.
- •Subjects must have congenital heart disease.
- •American Society of Anesthesiology (ASA) Physical Status 1-
- •Subjects scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 3hours.
- •Subjects spontaneously ventilating with a natural airway scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 2 hours.
- •Subjects must have reliable intravascular access from which to draw blood samples.
排除标准
- •History of allergic reaction or sensitivity to dexmedetomidine.
- •Nasal pathology preventing the administration of drug.
- •Patients that are on maintenance medications that could inhibit or induce the CYP2A6 enzyme.
- •Cardiac conduction abnormalities defined as second or third degree heart block or pacemaker dependence.
- •Bradycardia, defined by age, upon arrival in the preoperative care area.
- •Hepatic dysfunction defined as a history of hepatic dysfunction AND an Alanine Aminotransferase (ALT) value greater than 2 times normal in the 6 months prior to study drug administration.
- •The subject has received dexmedetomidine or clonidine within 1 week of the study date.
- •Patients previously enrolled in this study.
- •Any investigational drug use within 30 days prior to enrollment.
- •Wards will not be eligible.
研究组 & 干预措施
Cohort 1
Cohort 1A:
- Dexmedetomidine 2 μg/kg
- Under general oral endotracheal anesthesia
- 7 subjects age >2 yo and ≤ 6 yo
- 7 subjects age ≥1 mo and ≤2 yo
Cohort 1B:
- Dexmedetomidine 2 μg/kg
- Under sedation with a natural airway
- 7 subjects age >2 yo and ≤ 6 yo
- 7 subjects age ≥1 mo and ≤2 yo
干预措施: Dexmedetomidine (Drug)
Cohort 2
- Dexmedetomidine 4 μg/kg
- Under general oral endotracheal anesthesia
- 7 subjects age >2 yo and ≤ 6 yo
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
Time of Peak Drug Concentration Level of Dexmedetomidine
时间窗: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. The time of peak drug concentration will be determined based on this data.
Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL
时间窗: Subjects were monitored for 6 hours after the administration of study drug.
Dose-limiting toxicities (DLT) include bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event possibly, probably, or definitely related to intranasal dexmedetomidine administration that occured after the administration of the intranasal dexmedetomidine and through the completion of PK sampling. Bradycardia, hypotension, or new intraventricular conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team as part of usual clinical care were not considered DLTs but were considered an adverse event. Any events that could not be explained by the intervention that the patient was undergoing were assumed to be related to the study drug.
Number of Samples Obtained Per Subject
时间窗: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. This is the number of samples obtained per subject.
Serum Drug Concentration Levels of Dexmedetomidine
时间窗: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
Following administration of atomized intranasal dexmedetomidine, serum samples will be obtained at the following times post administrations: 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. Peak concentration will be determined based on this data.
次要结局
未报告次要终点
研究者
Kelly Grogan
Attending Physician, Anesthesia and Critical Care Medicine, Principal Investigator
Children's Hospital of Philadelphia