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| Name | Class |
|---|---|
| Lund University | OTHER |
| Karolinska Institutet | OTHER |
| Helsinki University Central Hospital | OTHER |
| Great Ormond Street Hospital for Children NHS Foundation Trust |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fentanyl | All infants in need of analgesia according to an algorithm based on pain assessment results will receive fentanyl as the first analgesic 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl | Drug | The dosing and administration of fentanyl will serve as the first drug intervention in infants in need of analgesia according to an algorithm based on pain scoring results. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of fentanyl and clonidine | Analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics | Repeated blood samples over a total of 4 - 7 days] |
| Neurophysiologic response; by single cortical events and their dynamics in relation to PK | 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. | From admission to the department until 4- 72 h after reaching normothermia.] |
| Neurophysiologic response; longer term brain function in relation to PK | Assessment of longer term brain function using measures of long range correlation and brain activity cycling. | From admission to the department until 4- 72 h after reaching normothermia |
| Neurophysiologic response; global brain network function in relation to PK | Assessment of global brain network function will be based on Activation Synchrony Index. | From admission to the department until 4- 72 h after reaching normothermia |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | |
| Change in pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) in relation to PK |
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Inclusion Criteria:
Exclusion Criteria:
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Term asphyxiated infants admitted to the NICU for hypothermic treatment according to national and international guidelines and in need for analgesia according to pain assessment scales.
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| Name | Affiliation | Role |
|---|---|---|
| Elisabeth Norman, MD | Region Skane and Lunds University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Skåne Uniersity Hospital | Lund | 221 85 | Sweden | |||
| Karolinska University Hospital |
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| ID | Term |
|---|---|
| D001238 | Asphyxia Neonatorum |
| D000377 | Agnosia |
| D001237 | Asphyxia |
| D007035 | Hypothermia |
| ID | Term |
|---|---|
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| D003000 | Clonidine |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D048288 | Imidazolines |
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| OTHER |
| Örebro University, Sweden | OTHER |
| The Swedish Research Council | OTHER_GOV |
| University of Colorado, Denver | OTHER |
| University of Tartu | OTHER |
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Whole blood
| Fentanyl and clonidine | Drug | In infants in need of further analgesia clonidine will be administered as an add on drug according to an algorithm based on pain scoring results. |
|
| 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 |
| Stockholm |
| 171 76 |
| Sweden |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D014947 | Wounds and Injuries |
| D001832 | Body Temperature Changes |
| D007093 |
| Imidazoles |
| D001393 | Azoles |