The PREVENT AGITATION Trial II - Children ≤1 Year

April 9, 2024 updated by: Arash Afshari, Rigshospitalet, Denmark
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

336

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 1 year (Child)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clonidine
Participants receive Clonidine solution for injection, 3 microg/kg, administered intravenously once over 2 minutes approximately 20 minutes before end of procedure. Injection is administered from a dilated solution of Clonidine 15 microg/mL (ie., 0.2 mL/kg).
Drug: Clonidine
Clonidine injection 3 mcg/kg once
Other Names:
  • Catapres
  • Catapresan
Placebo Comparator: Placebo
Participants receive Sodium Chloride isotonic (9mg/mL) solution for injection administered intravenously once over 2 minutes approximately 20 minutes before end of procedure. Dosage is administered according to weight: 0.2 mL/kg.
Drug: Sodium chloride
Sodium chloride 0.9 % injection 0.2 mL/kg once
Other Names:
  • Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of emergence agitation during stay in postanaesthetic care unit (PACU)
Time Frame: 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.
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.
Compartmental clearance for pharmacokinetic profiling.
Time Frame: 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.
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.
Volume of distribution for pharmacokinetic profiling.
Time Frame: 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.
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.
T1/2 for pharmacokinetic profiling.
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants with postoperative pain
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Proportion of participants with Postoperative Nausea and Vomiting (PONV)
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Safety and tolerability of clonidine in infants 3-12 months of age: proportion of participants with adverse events of clinical interest
Time Frame: 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.
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.
Mean sedation level in PACU
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Mean amount of additional opioid administered in PACU
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Mean time to administration of opioid i PACU
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Mean time to postoperative feeding/oral intake
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Mean time to awakening
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Mean time to discharge readiness
Time Frame: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Investigators

  • Principal Investigator: Arash Afshari, PhD, Rigshospitalet, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2021

Primary Completion (Estimated)

January 31, 2026

Study Completion (Estimated)

January 31, 2026

Study Registration Dates

First Submitted

October 13, 2021

First Submitted That Met QC Criteria

October 22, 2021

First Posted (Actual)

October 25, 2021

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20200708
  • 2020-005409-26 (EudraCT Number)

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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