Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants

NCT03177980 | Completed

• 1 other identifier: 2015-002470-20
• Study Type: observational
• Target: 49
• Locations: 1 country
• Sites: 2

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.

Conditions

Asphyxia Neonatorum

Keywords

Term infants; Analgesia; fentanyl; clonidine; pharmacokinetics; sedation; pharmacodynamics; neurophysiology; pharmacogenetics; asphyxia; hypothermia

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (4)

• 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

  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

Study Arms (2)

Fentanyl

All infants in need of analgesia according to an algorithm based on pain assessment results will receive fentanyl as the first analgesic drug.

Drug: Fentanyl

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.

Drug: Fentanyl and clonidine

Interventions

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.

Fentanyl

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.

Fentanyl and Clonidine

Eligibility Criteria

• Age: 36 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Region Skane: lead
• Lund University: collaborator
• Karolinska Institutet: collaborator
• Helsinki University Central Hospital: collaborator
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator
• Örebro University, Sweden: collaborator
• The Swedish Research Council: collaborator
• University of Colorado, Denver: collaborator
• University of Tartu: collaborator

Study Sites (2)

Skåne Uniersity Hospital

Lund, 221 85, Sweden

Location

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Asphyxia Neonatorum; Agnosia; Asphyxia; Hypothermia

Interventions

Fentanyl; Clonidine

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Death; Pathologic Processes; Wounds and Injuries; Body Temperature Changes

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazolines; Imidazoles; Azoles

Study Officials

• Elisabeth Norman, MD

  Region Skane and Lunds University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: June 6, 2017
• Study Start: April 24, 2017
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: June 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)