Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care

NCT04928651 | Completed DMC

• 1 other identifier: 2017-005091-26
• Study Type: observational
• Target: 40
• 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 clonidine administered for analgesia and sedation to preterm newborn infants receiving neonatal intensive care. Phase 3 - therapeutic confirmatory study

Conditions

Intensive Care, Neonatal; Analgesia; Hypnotics and Sedatives

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetics (PK) of clonidine; S-concentration

  Clonidine analyses will be performed with LC-MS standard assay on a Waters ultra-pressure liquid chromatography (UPLC)-MS/MS system and then statistically analysed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics

  Repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion

• Pharmacokinetics (PK) of clonidine; elimination half-time

  Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics

  Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion

• Pharmacokinetics (PK) of clonidine; clearance

  Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics

  Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion

• Pharmacokinetics (PK) of clonidine; volume of distribution

  Statistical analyses will be performed with NONMEM (Non-linear Mixed Effect Modelling) populationbased PK statistics

  Data from repeated blood samples (5 minutes after the loading dose, just before start of the clonidine infusion and at 1 hour, 24 hours, 48 hours and 72 hours after start of the infusion

• Neurophysiologic amplitude-integrated EEG response 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 30 minutes before start of treatment until 72 hours after start of treatment.

• Neurophysiologic amplitude-integrated EEG 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 30 minutes before start of treatment until 72 hours after start of treatment.

• Neurophysiologic amplitude-integrated EEG response; assessment of global brain network function in relation to PK

  Assessment of global brain network function will be based on Activation Synchrony Index.

  From 30 minutes before start of treatment until 72 hours after start of treatment.

Secondary Outcomes (11)

• Change in/association between heart rate in relation to PK .

  From 30 minutes before start of treatment until 72 hours.

• Change in/association between blood pressure (systolic, diastolic and mean arterial blood pressure) in relation to PK .

  From 30 minutes before start of treatment until 72 hours.

• Change in/association between peripheral oxygen saturation in relation to PK .

  From 30 minutes before start of treatment until 72 hours.

• Change in NIRS (near-infrared spectroscopy) response in relation to PK .

  From 30 minutes before start of treatment until 72 hours.

• Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (Astrid Lindgrens and Lund childrens hospitals Pain and stress assessment scale for Preterm and Sick newborn infants, ALPS-Neo) in relation to PK.

  From 30 minutes before start of treatment until 72 hours.

Study Arms (1)

Clonidine

Preterm infants (\< gw 37+0) who are in need for analgesic or sedative medication will receive treatment with clonidine according to an algorithm based on pain and sedative scoring results

Drug: Clonidine

Interventions

Clonidine DRUG

Clonidine will be administered to preterm infants in need of analgesia and sedation; either as the primary drug for comfort and light sedation or as an "add-on" drug to opioids according to an algorithm based on pain and sedative scoring results. Opioids are mostly given to postoperative patients. These drugs (morphine or fentanyl) will not be studied, but a baseline PK sample will be taken to correlate to the baseline aEEG.

Clonidine

Eligibility Criteria

• Age: Up to 37 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Sick preterm infants admitted to the NICU in need for analgesic or sedative medication according to clinical judgment.

You may qualify if:

• Preterm infants (\< gw 37+0) who are in need for analgesic or sedative medication according to clinical judgment (scoring with pain assessment scales; ALPS-Neo and Comfort-Neo)
• Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
• Informed and written parental consent

You may not qualify if:

• Hemodynamic instability (same as in clinical routine).
• Cardiac malformations in need for postnatal surgery.
• Any serious medical condition or ethical issues that could, in the Investigators opinion, interfere with the study procedures.

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 Tartu: collaborator
• University of Colorado, Denver: collaborator

Study Sites (2)

Skane University Hospital

Lund, 221 85, Sweden

Location

Marco Bartocci

Stockholm, 171 76, Sweden

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Agnosia

Interventions

Clonidine

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Elisabeth Norman, MD

  Region Skane

  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: March 23, 2018
• First Posted: June 16, 2021
• Study Start: April 6, 2018
• Primary Completion: May 13, 2022
• Study Completion: May 13, 2022
• Last Updated: August 4, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)