Clinical trial NCT04928651: Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care
Official title: Clonidine for Analgesia to Preterm Infants During Neonatal Intensive Care - a Prospective Pharmacokinetic/Pharmacodynamic/Pharmacogenetic Observational Study. Cohort 2 in The SANNI Project
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intensive Care, Neonatal
Analgesia
Hypnotics and Sedatives
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
name: Karolinska Institutet
name: Helsinki University Central Hospital
name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Örebro University, Sweden
name: The Swedish Research Council
name: University of Tartu
name: University of Colorado, Denver
First posted: 2021-06-16
Enrollment: 40
Sex: ALL
Maximum age (years): 37
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Sick preterm infants admitted to the NICU in need for analgesic or sedative medication according to clinical judgment.

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

Detailed description: All preterm infants that are admitted to the study neonatal intensive care units (NICUs) for neonatal intensive care 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 clonidine according to clinical judgment (pain scores) and as decided by the responsible clinical doctor. The dosing and administration of the drug 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 follow-up (neurologic examination and magnetic resonance imaging, MRI) are the same as for all preterm infants according to local and national guidelines.

In total 100 infants will be included.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Pharmacokinetics (PK) of clonidine; S-concentration
timeFrame: 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
measure: Pharmacokinetics (PK) of clonidine; elimination half-time
timeFrame: 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
measure: Pharmacokinetics (PK) of clonidine; clearance
timeFrame: 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
measure: Pharmacokinetics (PK) of clonidine; volume of distribution
timeFrame: 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
measure: Neurophysiologic amplitude-integrated EEG response in relation to PK
timeFrame: From 30 minutes before start of treatment until 72 hours after start of treatment.
measure: Neurophysiologic amplitude-integrated EEG response; longer term brain function in relation to PK
timeFrame: From 30 minutes before start of treatment until 72 hours after start of treatment.
measure: Neurophysiologic amplitude-integrated EEG response; assessment of global brain network function in relation to PK
timeFrame: From 30 minutes before start of treatment until 72 hours after start of treatment.
Secondary outcomes:
measure: Change in/association between heart rate in relation to PK .
timeFrame: From 30 minutes before start of treatment until 72 hours.
measure: Change in/association between blood pressure (systolic, diastolic and mean arterial blood pressure) in relation to PK .
timeFrame: From 30 minutes before start of treatment until 72 hours.
measure: Change in/association between peripheral oxygen saturation in relation to PK .
timeFrame: From 30 minutes before start of treatment until 72 hours.
measure: Change in NIRS (near-infrared spectroscopy) response in relation to PK .
timeFrame: From 30 minutes before start of treatment until 72 hours.
measure: 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.
timeFrame: From 30 minutes before start of treatment until 72 hours.
measure: Change in pain, stress and behavioral state as assessed with a pain scale for continuous pain/stress (The COMFORT-Neo scale) in relation to PK
timeFrame: From 30 minutes before start of treatment until 72 hours.
measure: Procedural pain response in relation to PK: assessed with change in galvanic skin response
timeFrame: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
measure: Procedural pain response in relation to PK: change in serum-cortisol
timeFrame: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
measure: Procedural pain response in relation to PK as assessed with the Premature Infant Pain Profile - revised, PIPP-R, a scale for assessment of procedural pain.
timeFrame: At one occasion during the study period (72 hours) when the analgesic treatment has not been changed the last six hours.
measure: Pharmacogenetic profile in relation to PK results how PK phenotypes depend on pharmacogenetic (PG) profiles.
timeFrame: One blood sample during the study period of 72 hours
measure: Pharmacogenetic profile in relation to PD results
timeFrame: One blood sample during the study period of 72 hours
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skane University Hospital
city: Stockholm
country: Sweden
facility: Marco Bartocci
Study officials:
affiliation: Region Skane
name: Elisabeth Norman, MD
role: PRINCIPAL_INVESTIGATOR
References: