Fentanyl and Clonidine for Analgesia During Hypothermia in Term Asphyxiated Infants

Asphyxia Neonatorum Clinical Trial

— SANNI 1  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03177980
• Other study ID #: 2015-002470-20
• Status: Completed
• Start date: April 24, 2017
• Est. completion date: April 1, 2021

Study information

• Verified date: June 2021
• Source: Region Skane
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 1, 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 36 Weeks and older

Eligibility

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.

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Hypothermia

Intervention

Drug:
• Fentanyl
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 and clonidine
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.

Locations

Country	Name	City	State
Sweden	Skåne Uniersity Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm

Sponsors (9)

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

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]
Primary	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.]
Primary	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
Primary	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	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.
Secondary	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.
Secondary	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
Secondary	Pharmacogenetic profile in relation to PK and PD results; how PK/PD phenotypes depend on pharmacogenetic (PG) profiles.		One blood sample during study