Clinical trial NCT03177980: Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants
Official title: Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 1 in The SANNI Project.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asphyxia Neonatorum
Keywords: Term infants
Analgesia
fentanyl
clonidine
pharmacokinetics
sedation
pharmacodynamics
neurophysiology
pharmacogenetics
asphyxia
hypothermia
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
name: Karolinska Institutet
name: Helsinki University Central Hospital
name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Örebro University, Sweden
name: The Swedish Research Council
name: University of Colorado, Denver
name: University of Tartu
First posted: 2017-06-06
Enrollment: 49
Sex: ALL
Minimum age (years): 36
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Pharmacokinetics (PK) of fentanyl and clonidine
timeFrame: Repeated blood samples over a total of 4 - 7 days]
measure: Neurophysiologic response; by single cortical events and their dynamics in relation to PK
timeFrame: From admission to the department until 4- 72 h after reaching normothermia.]
measure: Neurophysiologic response; longer term brain function in relation to PK
timeFrame: From admission to the department until 4- 72 h after reaching normothermia
measure: Neurophysiologic response; global brain network function in relation to PK
timeFrame: From admission to the department until 4- 72 h after reaching normothermia
Secondary outcomes:
measure: 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
timeFrame: From admission to the department until 4- 72 h after reaching normothermia.
measure: Change in pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) in relation to PK
timeFrame: From admission to the department until 4- 72 h after reaching normothermia.
measure: 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.
timeFrame: Once during stable treatment with hypothermia and 6 hours of unchanged medication
measure: Pharmacogenetic profile in relation to PK and PD results; how PK/PD phenotypes depend on pharmacogenetic (PG) profiles.
timeFrame: One blood sample during study
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne Uniersity Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Region Skane and Lunds University
name: Elisabeth Norman, MD
role: PRINCIPAL_INVESTIGATOR
References: