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The PREVENT AGITATION Trial II - Children ≤1 Year

Primary Purpose

Emergence Delirium

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Clonidine
Sodium chloride
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Emergence Delirium focused on measuring Anesthesia, Clonidine, Sevoflurane, Pharmacokinetics, Postoperative Nausea and Vomiting, Postoperative Pain, Infant

Eligibility Criteria

3 Months - 12 Months (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Copenhagen University Hospital, RigshospitaletRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Clonidine

Placebo

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

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.
Compartmental clearance for pharmacokinetic profiling.
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
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
T1/2 for pharmacokinetic profiling.
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L

Secondary Outcome Measures

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.
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.
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).
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.
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.
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.
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.
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.
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.

Full Information

First Posted
October 13, 2021
Last Updated
March 23, 2023
Sponsor
Rigshospitalet, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT05091242
Brief Title
The PREVENT AGITATION Trial II - Children ≤1 Year
Official Title
The PREVENT AGITATION Trial II - Children ≤1 Year
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 25, 2021 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Emergence Delirium
Keywords
Anesthesia, Clonidine, Sevoflurane, Pharmacokinetics, Postoperative Nausea and Vomiting, Postoperative Pain, Infant

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Part A: Open-label pharmacokinetic part (n =16) Part B: Randomized placebo-controlled part (n =320)
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
336 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Clonidine
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Clonidine
Other Intervention Name(s)
Catapresan, Catapres
Intervention Description
Clonidine injection 3 mcg/kg once
Intervention Type
Drug
Intervention Name(s)
Sodium chloride
Other Intervention Name(s)
Normal saline
Intervention Description
Sodium chloride 0.9 % injection 0.2 mL/kg once
Primary Outcome Measure Information:
Title
Incidence of emergence agitation during stay in postanaesthetic care unit (PACU)
Description
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.
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.
Title
Compartmental clearance for pharmacokinetic profiling.
Description
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
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.
Title
Volume of distribution for pharmacokinetic profiling.
Description
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
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.
Title
T1/2 for pharmacokinetic profiling.
Description
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
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.
Secondary Outcome Measure Information:
Title
Proportion of participants with postoperative pain
Description
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.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Proportion of participants with Postoperative Nausea and Vomiting (PONV)
Description
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.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Safety and tolerability of clonidine in infants 3-12 months of age: proportion of participants with adverse events of clinical interest
Description
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).
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.
Title
Mean sedation level in PACU
Description
Participants will be assessed for alertness on the University of Michigan Sedation Scale (UMSS) every 15 minutes during PACU stay.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Mean amount of additional opioid administered in PACU
Description
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.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Mean time to administration of opioid i PACU
Description
Time in minutes to first administration of opioid will be assessed for each participant during PACU stay.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Mean time to postoperative feeding/oral intake
Description
Time in minutes from administration of intervention to first time point at which participant is eating during PACU stay, evaluated every 15 minutes.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Mean time to awakening
Description
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.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.
Title
Mean time to discharge readiness
Description
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.
Time Frame
From admission to PACU to discharge from PACU, up to app. 4 hours.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bettina Nielsen, PhD
Phone
+4535459546
Email
bettina.nygaard.nielsen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Anne Louise B Garioud, MD
Phone
+4535456243
Email
anne.louise.de.barros.garioud@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arash Afshari, PhD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Copenhagen University Hospital, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bettina Nielsen, PhD
Phone
+4535459546
Email
bettina.nygaard.nielsen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Anne Louise B Garioud, MD
Phone
+4535456243
Email
anne.louise.de.barros.garioud@regionh.dk

12. IPD Sharing Statement

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The PREVENT AGITATION Trial II - Children ≤1 Year

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