Clinical trial NCT05091242: The PREVENT AGITATION Trial II - Children ≤1 Year
Official title: The PREVENT AGITATION Trial II - Children ≤1 Year
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Emergence Delirium
Keywords: Anesthesia
Clonidine
Sevoflurane
Pharmacokinetics
Postoperative Nausea and Vomiting
Postoperative Pain
Infant
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2021-10-25
Enrollment: 336
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A: Open-label pharmacokinetic part (n =16) Part B: Randomized placebo-controlled part (n =320)
Primary purpose: PREVENTION

Brief summary: Emergence agitation is a clinical condition in which the child experiences a variety of behavioural disturbances including crying, thrashing, and disorientation during early awakening from anaesthesia. Emergence agitation is a common challenge in children with a reported incidence of approximately 25% ranging from 10 to 80 %. Clonidine is often used off-label in paediatric anaesthesia e.g. sedation in the intensive care unit, prevention of withdrawal symptoms after long-term sedation, as premedication before induction of anaesthesia or as treatment/prevention of emergence agitation. The study is designed as a randomised, placebo-controlled clinical trial evaluating efficacy and safety of a single dose of intraoperative clonidine in children 3-12 months, including pharmacokinetics.


Eligibility criteria: Inclusion Criteria:

* Paediatric patients (male and female), aged 3- ≤ 12 months
* Scheduled general anaesthesia with sevoflurane and opioid. Induction with propofol is optional
* The legally acceptable representative for the study participant provides written informed consent/assent for the trial

Exclusion Criteria:

* ASA \>2
* Cardiac, neuro and trauma surgery
* Ex-premature (\<37 weeks) • Premedication with clonidine
* Intubated prior to scheduled anaesthesia or is expected to require intubation after the procedure
* Critical illness incl. hemodynamic instability (inotropic drugs needed)
* Bleeding requiring transfusion prior to scheduled anaesthesia
* Planned for a postoperative nurse-controlled analgesia pump including a continuous infusion of opioid
* Malignant disease
* Cardiac disease incl. arrhythmia
* Chronic lung disease that may influence study results or study participation in the opinion of the Investigator or may comprise safety and well-being of the patient
* Mental retardation
* Neurological disease including symptoms similar to emergence agitation
* Has or is suspected of having a family or personal history of malignant hyperthermia
* Has or is suspected of having an allergy to study treatment or its excipients
* Any condition that can in opinion of the Investigator, deteriorate safety and well-being of the patients or interfere with pharmacokinetic data
* Positive Covid-19 test or clinical suspicion of Covid-19 (according to current local guidelines)

Primary outcomes:
measure: Incidence of emergence agitation during stay in postanaesthetic care unit (PACU)
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours. Emergence agitation is considered present ("Yes"), if Watcha score>2 at ANY time point within the given time frame.
measure: Compartmental clearance for pharmacokinetic profiling.
timeFrame: Samples will be collected at baseline and at 5, 15, 30, and 60 minutes post dosage and just prior prior to removal of iv-access ie., at latest 120-240 min post dosage.
measure: Volume of distribution for pharmacokinetic profiling.
timeFrame: Samples will be collected at baseline and at 5, 15, 30, and 60 minutes post dosage and just prior prior to removal of iv-access ie., at latest 120-240 min post dosage.
measure: T1/2 for pharmacokinetic profiling.
timeFrame: Samples will be collected at baseline and at 5, 15, 30, and 60 minutes post dosage and just prior prior to removal of iv-access ie., at latest 120-240 min post dosage.
Secondary outcomes:
measure: Proportion of participants with postoperative pain
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Proportion of participants with Postoperative Nausea and Vomiting (PONV)
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Safety and tolerability of clonidine in infants 3-12 months of age: proportion of participants with adverse events of clinical interest
timeFrame: From administration of intervention through end of anaesthesia and PACU stay (up to app. 4 hours). Supplemental Adverse Event follow-up at 24 hours, 48 hours in case of ongoing adverse events and at 30 days post-intervention.
measure: Mean sedation level in PACU
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Mean amount of additional opioid administered in PACU
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Mean time to administration of opioid i PACU
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Mean time to postoperative feeding/oral intake
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Mean time to awakening
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
measure: Mean time to discharge readiness
timeFrame: From admission to PACU to discharge from PACU, up to app. 4 hours.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Arash Afshari, PhD
role: PRINCIPAL_INVESTIGATOR
References: