Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 1 in The SANNI Project.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Region Skane
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Pharmacokinetics (PK) of fentanyl and clonidine
研究概览
简要总结
A prospective pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) observation study, including the PK/PD/PG relationship, in fentanyl and clonidine administered for analgesia and sedation to term newborn asphyxiated infants receiving hypothermic treatment in the NICU.
详细描述
All patients that are admitted to the study neonatal intensive care units (NICUs) for hypothermic treatment due to perinatal asphyxia are potential study patients, and their parents will be asked for consent.
The patient will be treated according to clinical guidelines and will be included in the study if in need for fentanyl and clonidine according to clinical judgment (HIE and pain scores) and as decided by the responsible clinical doctor. The dosing and administration of the drugs will be implemented according to an algorithm based on pain scoring results.
Apart from extra blood sampling, the bedside monitoring, investigations (electroencephalography (EEG), echocardiography (ECG), ultrasound of the brain and magnetic resonance imaging, (MRI)) and follow-up (neurologic examination) are the same as for all infants receiving hypothermia according to national and international guidelines. A brief standardised pain stimulation will be performed as part of the pain and stress assessment.
In total 50 infants will be included.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 36 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Term infants (≥ gw 36+0) who, according to national guidelines (6), will receive hypothermic treatment following perinatal asphyxia, and are in need for analgesic or sedative medication according to clinical judgment based on Thomsons score and ALPS-Neo.
- •Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
- •Informed and written parental consent.
排除标准
- •Atrioventricular (AV)- block I-III or heart rate < 70 .
- •Serious coronary heart disease with need for postnatal surgery
- •Mean arterial blood pressure <35 mmHg despite adequate treatment.
研究组 & 干预措施
Fentanyl
All infants in need of analgesia according to an algorithm based on pain assessment results will receive fentanyl as the first analgesic drug.
干预措施: Fentanyl (Drug)
Fentanyl and Clonidine
Infants in need of further analgesia according to an algorithm based on pain assessment results will receive fentanyl and clonidine as the analgesic drugs.
干预措施: Fentanyl and clonidine (Drug)
结局指标
主要结局
Pharmacokinetics (PK) of fentanyl and clonidine
时间窗: Repeated blood samples over a total of 4 - 7 days]
Analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Neurophysiologic response; by single cortical events and their dynamics in relation to PK
时间窗: From admission to the department until 4- 72 h after reaching normothermia.]
Analyse of single cortical events and their dynamics based on burst detection and measuring features of individual bursts as well as their mass statistical behaviour over time.
Neurophysiologic response; longer term brain function in relation to PK
时间窗: From admission to the department until 4- 72 h after reaching normothermia
Assessment of longer term brain function using measures of long range correlation and brain activity cycling.
Neurophysiologic response; global brain network function in relation to PK
时间窗: From admission to the department until 4- 72 h after reaching normothermia
Assessment of global brain network function will be based on Activation Synchrony Index.
次要结局
- Change in pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) in relation to PK(From admission to the department until 4- 72 h after reaching normothermia.)
- Procedural pain response at a short standardized pain stimulation; as assessed with change in galvanic skin response, change in serum-cortisol and scored by a procedural pain assessment scale (PIPP-R) in relation to PK.(Once during stable treatment with hypothermia and 6 hours of unchanged medication)
- Pharmacogenetic profile in relation to PK and PD results; how PK/PD phenotypes depend on pharmacogenetic (PG) profiles.(One blood sample during study)
- Change in/association between physiological parameters (heart rate, blood pressure, peripheral oxygen saturation and NIRS (near-infrared reflectance spectroscopy near-infrared spectroscopy) parameters) in relation to PK parameters(From admission to the department until 4- 72 h after reaching normothermia.)