Dexmedetomidine for Analgosedation to Newborn Infants During Neonatal Intensive Care

Withdrawn

• Conditions: Hypnotics and Sedatives; Analgesia; Intensive Care, Neonatal
• Interventions: Drug: dexmedetomidine

• Registration Number: NCT06482775
• Lead Sponsor: Region Skane

Brief Summary

A prospective pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) observation study, including the PK/PD/PG relationship, on dexmedetomidine administered for analgesia and sedation to postsurgical and other newborn sick infants needing the drug for clinical reasons during neonatal intensive care. Phase III - therapeutic confirmatory study.

Detailed Description

The patients will be treated according to clinical guidelines and judgement as decided by the responsible clinical doctor.

The dosing and administration of dexmedetomidine will be implemented according to an algorithm based on pain scoring results.

Apart from extra blood sampling and extended bedside monitoring for amplitude-integrated EEG (aEEG), Near InfraRed Spectroscopy (NIRS), and Galvanic Skin Response (GSR) the care is according to clinical routine.

In total 100 infants will be included.

Study Timeline

• Study First Submitted: 2020-08-04
• Status Verified: 2021-06
• Study Start: 2021-06-01
• Primary Completion: 2021-12-01
• Study Completion: 2021-12-31
• Study First Submitted QC: 2024-06-27
• Last Update Submitted: 2024-06-27
• Study First Posted: 2024-07-01
• Last Update Posted: 2024-07-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Newborn infants: - born 34+0 gw with a need for dexmedetomidine for analgesic and/or sedative treatment after postnatal surgical correction of congenital malformations and who will be cared for in the PICU (postoperative intensive care unit) and in a some few cases in the NICU (neonatal intensive care unit), or
• with a corresponding age of 37 gw, who are in need for dexmedetomidine according to clinical judgment and cared for in the NICU.
• Existing arterial or venous cannulas/catheters for repeated nontraumatic blood sampling
• Informed and written parental consent obtained before study start.

Exclusion Criteria

• Infant older than age corresponding to gw 46+0
• Previous treatment with the dexmedetomidine within 72 hours (only for postoperative infants).
• Congenital cardiac malformations requiring surgery on extracorporeal circulation and treatment with hypothermia.
• Ongoing renal replacement treatment
• Any serious medical condition or ethical issues that could, in the investigators opinion, interfere with the study procedures.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
dexmedetomidine	dexmedetomidine	Infusion of dexmedetomidine 4 microgram/mL.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) of dexmedetomidine	Repeated blood samples (5 minutes after the loading dose until 12 hours after stop of infusion)	The plasma concentration will be analysed and then further reported using NONMEM® (Non-linear Mixed Effect Modelling) population-based PK modelling.
Neurophysiologic response; global brain network function in relation to PK	Baseline until 12 hours after stop of infusion	Assessment of global brain network function will be based on Activation Synchrony Index.

Secondary Outcome Measures

Name	Time	Method
Change in mean arterial blood pressure, MABP, (hemodynamic response) in relation to PK (PK/PD)	Baseline until 12 hours after stop of infusion	MABP will be monitored 1/second according to clinical routine in the neonatal intensive care, and concomitantly downloaded into the aEEG (amplitude integrated electroencephalography) monitor. The change will be described as percentage increase/decrease. The change from baseline response in MABP using longitudinal models of data on these endpoints following dexmedetomidine administration using a population PK/PD approach.
Procedural pain response in relation to PK: assessed with change in galvanic skin response	Once during treatment with dexmedetomidine	Procedural pain response at a short standardized pain stimulation;
Change in heart rate, HR, (hemodynamic response) in relation to PK (PK/PD)	Baseline until 12 hours after stop of infusion	HR will be monitored 1/second according to clinical routine in the neonatal intensive care, and concomitantly downloaded into the aEEG (amplitude integrated electroencephalography) monitor. The change will be described as percentage increase/decrease. The change from baseline response in heart rate using longitudinal models of data on these endpoints following dexmedetomidine administration using a population PK/PD approach.
Change in/association between Near Infrared spectroscopy, NIRS, in relation to PK.	Once per second (from baseline until 12 hours after stop of infusion)	NIRS will be monitored 1/second according to clinical routine in the neonatal intensive care, and concomitantly downloaded into the aEEG (amplitude integrated electroencephalography) monitor. The change will be described as percentage increase/decrease

Trial Locations

Locations (2)

Karolinska Universitetssjukhuset; 🇸🇪 Stockholm, Sweden

Skane University Hospital; 🇸🇪 Lund, Sweden