The PREVENT AGITATION Trial II - Children ≤1 Year

Emergence Delirium Clinical Trial

Official title:

The PREVENT AGITATION Trial II - Children ≤1 Year

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05091242
• Other study ID #: 20200708
• Secondary ID: 2020-005409-26
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 25, 2021
• Est. completion date: January 31, 2026

Study information

• Verified date: April 2024
• Source: Rigshospitalet, Denmark
• Contact: Bettina Nielsen, PhD
• Phone: +4535459546
• Email: bettina.nygaard.nielsen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 336
• Est. completion date: January 31, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 12 Months

Eligibility

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)

Related Conditions & MeSH terms

• Emergence Delirium

Intervention

Drug:
• Clonidine
Clonidine injection 3 mcg/kg once
• Sodium chloride
Sodium chloride 0.9 % injection 0.2 mL/kg once

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital, Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of emergence agitation during stay in postanaesthetic care unit (PACU)	Participants will be assessed on Watcha scale (1=calm, 4=agitated and thrashing around) every 15 minutes from arrival to PACU till discharge therefrom. Emergence agitation is defined dichotomously as Yes/No, Yes being if any Watcha score >2.	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.
Primary	Compartmental clearance for pharmacokinetic profiling.	Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L	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.
Primary	Volume of distribution for pharmacokinetic profiling.	Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L	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.
Primary	T1/2 for pharmacokinetic profiling.	Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L	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	Proportion of participants with postoperative pain	Participants will be assessed on Faces Legs Activity Cry Consolability (FLACC) scale every 15 minutes from arrival to PACU till discharge therefrom. Postoperative pain is defined as any FLACC score > 3 during PACU stay.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Proportion of participants with Postoperative Nausea and Vomiting (PONV)	Participants will be assessed for PONV every 15 minutes during PACU stay. No validated scale for assessment of PONV exists in this age group and PONV will be assessed by dichotomously as "Yes" or "No". While vomiting is obvious, nausea may be considered if participant refuses to eat and other causes are ruled out.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Safety and tolerability of clonidine in infants 3-12 months of age: proportion of participants with adverse events of clinical interest	Composite outcome combining as assessed by investigator for each participant any clinically relevant hypotension (ie., necessitating intervention), clinically relevant bradycardia (ie., necessitating intervention), clinically relevant apnoea (ie., unexplained cessation of breathing for 20 seconds or longer, or a shorter respiratory pause associated with bradycardia, cyanosis, and/or marked hypotonia).	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.
Secondary	Mean sedation level in PACU	Participants will be assessed for alertness on the University of Michigan Sedation Scale (UMSS) every 15 minutes during PACU stay.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Mean amount of additional opioid administered in PACU	The opioid sparing effect will be evaluated by assessing the amount of additional opioid administered to each participant for postoperative pain during the PACU stay calculated as morphine equivalents.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Mean time to administration of opioid i PACU	Time in minutes to first administration of opioid will be assessed for each participant during PACU stay.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Mean time to postoperative feeding/oral intake	Time in minutes from administration of intervention to first time point at which participant is eating during PACU stay, evaluated every 15 minutes.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Mean time to awakening	Time in minutes from administration of intervention to time point at which participant is awake in PACU, evaluated every 15 minutes. If child is not awake 2 hours after arrival, an awakening attempt will be initiated.	From admission to PACU to discharge from PACU, up to app. 4 hours.
Secondary	Mean time to discharge readiness	Time in hours from arrival in PACU to time point at which participant fulfills local PACU discharge criteria as judged by physician, evaluated every 15 minutes.	From admission to PACU to discharge from PACU, up to app. 4 hours.