Emergence DeliriumPhase 2/3NCT05091242
The PREVENT AGITATION Trial II - Children ≤1 Year
A Phase 2/3 study testing Clonidine and Sodium chloride in people with Emergence Delirium, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 3 to 12 months
- Conditions the study is for
- Emergence Delirium
- What is being tested?
- Clonidine and Sodium chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 336 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 25 Oct 2021to 31 Jan 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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)
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Australia1 site, 1 recruiting
- Recruiting
Perth Children's Hospital, Department of Anaesthesia and Pain Medicine
Perth, Nedlands, WA 6009
Britta von Ungern-Sternberg, Professor, 0061 6456 2222, Britta.Regli-VonUngern@health.wa.gov.au
Denmark1 site, 1 recruiting
- Recruiting
Copenhagen University Hospital, Rigshospitalet
Copenhagen, 2100
Bettina Nielsen, PhD, +4535459546, bettina.nygaard.nielsen@regionh.dk
Anne Louise B Garioud, MD, +4535456243, anne.louise.de.barros.garioud@regionh.dk
About this study
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.
- Conditions
- Emergence Delirium
- Being tested
- Clonidine, Sodium chloride
- Keywords
- Anesthesia, Clonidine, Sevoflurane, Pharmacokinetics, Postoperative Nausea and Vomiting, Postoperative Pain, Infant
- Medical subject headings
- Emergence Delirium, Postoperative Nausea and Vomiting, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClonidineDrug
Also called Catapresan, Catapres
Clonidine injection 3 mcg/kg once
Sodium chlorideDrug
Also called Normal saline
Sodium chloride 0.9 % injection 0.2 mL/kg once
| Study group | Role | What they receive |
|---|---|---|
| Clonidine | Experimental | 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). Receives: Drug: Clonidine |
| Placebo | Placebo comparator | 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. Receives: Drug: Sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
Measured: 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.
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
Measured: 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.
Pharmacokinetic sampling will be performed in 1 mL EDTA tubes and analysed for clonidine plasma concentration in migrog/L
Measured: 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 (9)
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.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Measured: 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
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).
Measured: 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
Participants will be assessed for alertness on the University of Michigan Sedation Scale (UMSS) every 15 minutes during PACU stay.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
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.
Measured: From admission to PACU to discharge from PACU, up to app. 4 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2021
- Study start25 Oct 2021
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Emergence DeliriumStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part A: Open-label pharmacokinetic part (n =16) Part B: Randomized placebo-controlled part (n =320)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 336 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arash Afshari, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Arash Afshari, PhD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05091242
- Sponsor's protocol ID
- 20200708
- Other IDs
- 2020-005409-26
- Status last verified
- Aug 2026
- First submitted
- 13 Oct 2021
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PREVENT AGITATION Trial II - Children ≤1 Year
- ClinicalTrials.gov ID
- NCT05091242
- Acronym / sponsor ID
- 20200708
- Conditions
- Emergence Delirium
- Keywords
- Anesthesia, Clonidine, Sevoflurane, Pharmacokinetics, Postoperative Nausea and Vomiting, Postoperative Pain, Infant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 336 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 25 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Part A: Open-label pharmacokinetic part (n =16) Part B: Randomized placebo-controlled part (n =320)
| Arm | Type | Receives |
|---|---|---|
| Clonidine | Experimental | Drug: ClonidineParticipants 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). |
| Placebo | Placebo comparator | Drug: Sodium chlorideParticipants 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. |
Who may qualify
- Ages
- 3 to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClonidineAlso: Catapresan, CatapresClonidine injection 3 mcg/kg once | Drug | Clonidine |
| Sodium chlorideAlso: Normal salineSodium chloride 0.9 % injection 0.2 mL/kg once | Drug | Placebo |
Primary outcome
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.
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
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
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
9 secondary outcomes
Proportion of participants with postoperative pain
Time frame: 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.
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.
Mean sedation level in PACU
Time frame: 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.
Mean time to administration of opioid i PACU
Time frame: 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.
Mean time to awakening
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Arash Afshari, PhD principal investigator
Copenhagen University Hospital, Rigshospitalet
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Clonidine and Sodium chloride in people with Emergence Delirium, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bettina Nielsen, PhD (+4535459546, bettina.nygaard.nielsen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.