Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 2 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
- 40
- 试验地点
- 2
- 主要终点
- Pharmacokinetics (PK) of clonidine; elimination half-time
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 clonidine administered for analgesia and sedation to preterm newborn infants receiving neonatal intensive care. Phase 3 - therapeutic confirmatory study
详细描述
All preterm infants that are admitted to the study neonatal intensive care units (NICUs) for neonatal intensive care 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 clonidine according to clinical judgment (pain scores) and as decided by the responsible clinical doctor. The dosing and administration of the drug 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 follow-up (neurologic examination and magnetic resonance imaging, MRI) are the same as for all preterm infants according to local and national guidelines.
In total 100 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
- — 至 37 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants (< gw 37+0) who are in need for analgesic or sedative medication according to clinical judgment (scoring with pain assessment scales; ALPS-Neo and Comfort-Neo)
- •Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
- •Informed and written parental consent
排除标准
- •Hemodynamic instability (same as in clinical routine).
- •Cardiac malformations in need for postnatal surgery.
- •Any serious medical condition or ethical issues that could, in the Investigators opinion, interfere with the study procedures.
研究组 & 干预措施
Clonidine
Preterm infants (< gw 37+0) who are in need for analgesic or sedative medication will receive treatment with clonidine according to an algorithm based on pain and sedative scoring results
干预措施: Clonidine (Drug)
结局指标
主要结局
Pharmacokinetics (PK) of clonidine; elimination half-time
时间窗: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Pharmacokinetics (PK) of clonidine; volume of distribution
时间窗: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Neurophysiologic amplitude-integrated EEG response; longer term brain function in relation to PK
时间窗: From 30 minutes before start of treatment until 72 hours after start of treatment.
Assessment of longer term brain function using measures of long range correlation and brain activity cycling.
Neurophysiologic amplitude-integrated EEG response; assessment of global brain network function in relation to PK
时间窗: From 30 minutes before start of treatment until 72 hours after start of treatment.
Assessment of global brain network function will be based on Activation Synchrony Index.
Pharmacokinetics (PK) of clonidine; clearance
时间窗: Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Pharmacokinetics (PK) of clonidine; S-concentration
时间窗: Repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion
Clonidine analyses will be performed with LC-MS standard assay on a Waters ultra-pressure liquid chromatography (UPLC)-MS/MS system and then statistically analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics
Neurophysiologic amplitude-integrated EEG response in relation to PK
时间窗: From 30 minutes before start of treatment until 72 hours after start of treatment.
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.
次要结局
- Procedural pain response in relation to PK: change in serum-cortisol(At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.)
- Procedural pain response in relation to PK: assessed with change in galvanic skin response(At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.)
- Pharmacogenetic profile in relation to PK results how PK phenotypes depend on pharmacogenetic (PG) profiles.(One blood sample during the study period of 72 hours)
- Pharmacogenetic profile in relation to PD results(One blood sample during the study period of 72 hours)
- Change in/association between heart rate in relation to PK .(From 30 minutes before start of treatment until 72 hours.)
- Procedural pain response in relation to PK as assessed with the Premature Infant Pain Profile - revised, PIPP-R, a scale for assessment of procedural pain.(At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.)
- Change in/association between blood pressure (systolic, diastolic and mean arterial blood pressure) in relation to PK .(From 30 minutes before start of treatment until 72 hours.)
- Change in/association between peripheral oxygen saturation in relation to PK .(From 30 minutes before start of treatment until 72 hours.)
- Change in NIRS (near-infrared spectroscopy) response in relation to PK .(From 30 minutes before start of treatment until 72 hours.)
- Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (Astrid Lindgrens and Lund childrens hospitals Pain and stress assessment scale for Preterm and Sick newborn infants, ALPS-Neo) in relation to PK.(From 30 minutes before start of treatment until 72 hours.)
- Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (The COMFORT-Neo scale) in relation to PK(From 30 minutes before start of treatment until 72 hours.)