Dexmedetomidine for Analgosedation to Newborn Infants During Neonatal Intensive Care

Dexmedetomidine for Analgosedation to Newborn Infants During Neonatal Intensive Care - a Prospective Pharmacokinetic/ Pharmacodynamic/ Pharmacogenetic Observational Study.Cohort 3 in The SANNI Project.

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.

Study Overview

• Status: Withdrawn
• Conditions: Analgesia; Hypnotics and Sedatives; Intensive Care, Neonatal
• Intervention / Treatment: Drug: dexmedetomidine

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 Type: Observational

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 221 85
    • Skane University Hospital
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Sick newborn infants in need of intensive care.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
dexmedetomidine; Infusion of dexmedetomidine 4 microgram/mL.	Drug: dexmedetomidine; The dosing and administration will be implemented according to an algorithm based on pain scoring results

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate, HR, (hemodynamic response) in relation to PK (PK/PD)	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.	Baseline until 12 hours after stop of infusion
Change in mean arterial blood pressure, MABP, (hemodynamic response) in relation to PK (PK/PD)	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.	Baseline until 12 hours after stop of infusion
Change in/association between Near Infrared spectroscopy, NIRS, in relation to PK.	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	Once per second (from baseline until 12 hours after stop of infusion)
Procedural pain response in relation to PK: assessed with change in galvanic skin response	Procedural pain response at a short standardized pain stimulation;	Once during treatment with dexmedetomidine

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: University of Colorado, Denver; Karolinska Institutet; Lund University; The Swedish Research Council; Helsinki University Central Hospital; Örebro University, Sweden; Great Ormond Street Hospital for Children NHS Foundation Trust; University of Tartu
• Investigators: Principal Investigator: Elisabeth Norman, MD, Region Skane

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): December 1, 2021
• Study Completion (Estimated): December 31, 2021

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2015-002506-37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No