Psychomotor AgitationPhase 4NCT02361476
Does Intraoperative Clonidine Reduce Post Operative Agitation in Children?
A Phase 4 study testing Clonidine in people with Psychomotor Agitation, run by Copenhagen University Hospital, Rigshospitalet at 3 sites in Denmark.
Trial summary
Clonidine is widely used off-label in children for several indications. Clonidine is used for treatment and/or prevention of postoperative agitation in children anaesthetised with Sevoflurane. Read more about this study
- Who is it for?
- Ages 1 year to 5 years
- Conditions the study is for
- Psychomotor Agitation
- What is being tested?
- Clonidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 379 participants
- Where
- 3 sitesDenmark
- Study dates
- Jan 2015to Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- scheduled for surgery with Sevoflurane as the choice of anesthesia.
Who cannot join
- ASA classification >2
- Premedication with Clonidine
- Ex-premature (born before week 37+0 AND <60 weeks old)
- Intubated before anaesthesia and/or no plans for extubation after anaesthesia.
- Critical illness with haemodynamic instability.
- Active bleeding.
Show all 14Show fewer
- Cancer.
- Cardiac diseases including arrhythmias.
- Malignant hyperthermia.
- Mental retardation.
- Neurological illness with agitation-like symptoms.
- Weight >50 kg.
- Allergy to Clonidine.
- Patients treated with methylphenidate / Concerta.
Trial locations and contacts
3 sites in 1 country.
Denmark3 sites
The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Region Sjælland, 2100
Køge Sygehus, Anæstesiologisk Afdeling
Køge, 4600
Anæstesiologisk afdeling, Vejle Sygehus
Vejle, 7100
About this study
Official title: Does Intraoperative Clonidine Reduce Post Operative Agitation in Children Anaesthetised With Sevoflurane? A RCT Including Pharmacokinetic Investigation.
Clonidine is widely used off-label in children for several indications. Clonidine is used for treatment and/or prevention of postoperative agitation in children anaesthetised with Sevoflurane. The investigators don´t have solid evidence for the effect and the investigators don´t have data for characterization of the pharmacokinetic profile among age-groups for children 1-6 years.
In this study the investigators want to investigate if IV Clonidine administered at the end of surgery can prevent/reduce postoperative agitation. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including a 30-day follow-up.
Read the detailed description
BACKGROUND:
Clonidine is widely used off-label in children for several indications such as treatment and/or prevention of postoperative agitation when anaesthetised with Sevoflurane. However, the current level of evidence in support of Clonidine treatment for postoperative agitation in children remains limited. In addition, the pharmacokinetic profile of intravenous Clonidine in children is not well characterized for age-groups.
METHODS/DESIGN:
In this prospective multicentre double-blinded randomized clinical trial, the investigators aim to investigate the impact of intravenous (IV) Clonidine administered at the end of surgery, on the incidence and degree of postoperative agitation. Children will be assigned to either the intervention or the placebo group. The allocation will be carried out centrally and stratified based on age and trial-site, with152 patients allocated to each group. In the intervention group, 3 micrograms per kg of IV clonidine is administered approximately 20 minutes before the expected completion of the surgery (as assessed by the surgeon). In the control group; Saline (placebo) is injected in equal quantity during surgery at the same time. The drugs are concealed in identical blinded ampoules.
The primary outcome is postoperative agitation measured on the Watcha scale. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including 30-day follow-up.
Twenty of the patients age 1-2 years and twenty age >2 years, with a peripheral venous access in place, will be allocated to drug assay sampling; enabling a compartmental PK analysis based on age group, using non-linear mixed effects models.
- Conditions
- Psychomotor Agitation
- Being tested
- Clonidine, Placebo
- Keywords
- Anaesthesia, Children, Clonidine, Sevoflurane, Postoperative agitation, Prevention, Pharmacokinetics, Safety
- Medical subject headings
- Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClonidineDrug
Also called catapresan
Injection - during surgery
PlaceboDrug
Also called NaCl
Injection - during surgery
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Clonidine : injection og 3 micg/kg IV during the operation. Receives: Drug: Clonidine |
| Placebo | Placebo comparator | Placebo : injection og equal amount of NaCl IV during the operation. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative Agitation
Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated
Measured: 1 day
Secondary outcomes (4)
Fentanyl and Morphine Requirements
Amount used
Measured: Recorded during the stay in the postoperative recovery room
Pain Assessment
Pain score used:
FLACC score = Face, Legs, Activity, Cry, Consolability Score ranges from 0 to 10 (severity increases with increasing score) Pain is FLACC score more than 3
Measured: recovery room - hours
First Administration of Fentanyl or Morphine
Time to administration
Measured: recovery room
Adverse Events
Measured: from intervention to discharge from the recovery room
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Psychomotor AgitationStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 379 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mogens Ydemann, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Steen Henneberg, MD, DMSc, Study director, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02361476
- Sponsor's protocol ID
- H - 2 - 2014 - 072
- Status last verified
- Sep 2018
- First submitted
- 1 Feb 2015
- Last updated
- 11 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pickard A, Davies P, Birnie K, Beringer R. Systematic review and meta-analysis of the effect of intraoperative alpha(2)-adrenergic agonists on postoperative behaviour in children. Br J Anaesth. 2014 Jun;112(6):982-90. doi: 10.1093/bja/aeu093. Epub 2014 Apr 11.
PubMed 24727829Ydemann M, Nielsen BN, Henneberg S, Jakobsen JC, Wetterslev J, Lauritsen T, Steen N, Edstrom B, Afshari A; PREVENT AGITATION Research Group. Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018 Jan;2(1):15-24. doi: 10.1016/S2352-4642(17)30127-X. Epub 2017 Nov 2.
PubMed 30169192Ydemann M, Nielsen BN, Wetterslev J, Henneberg S, Lauritsen T, Steen N, Edstrom B, Afshari A. Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial. Dan Med J. 2016 Jun;63(6):A5234.
PubMed 27264945
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Intraoperative Clonidine Reduce Post Operative Agitation in Children Anaesthetised With Sevoflurane? A RCT Including Pharmacokinetic Investigation.
- ClinicalTrials.gov ID
- NCT02361476
- Acronym / sponsor ID
- H - 2 - 2014 - 072
- Conditions
- Psychomotor Agitation
- Keywords
- Anaesthesia, Children, Clonidine, Sevoflurane, Postoperative agitation, Prevention, Pharmacokinetics, Safety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 379 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 11 Feb 2015 (estimated)
- Results
- Posted 11 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clonidine is widely used off-label in children for several indications. Clonidine is used for treatment and/or prevention of postoperative agitation in children anaesthetised with Sevoflurane. The investigators don´t have solid evidence for the effect and the investigators don´t have data for characterization of the pharmacokinetic profile among age-groups for children 1-6 years.
In this study the investigators want to investigate if IV Clonidine administered at the end of surgery can prevent/reduce postoperative agitation. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including a 30-day follow-up.
Detailed description
BACKGROUND:
Clonidine is widely used off-label in children for several indications such as treatment and/or prevention of postoperative agitation when anaesthetised with Sevoflurane. However, the current level of evidence in support of Clonidine treatment for postoperative agitation in children remains limited. In addition, the pharmacokinetic profile of intravenous Clonidine in children is not well characterized for age-groups.
METHODS/DESIGN:
In this prospective multicentre double-blinded randomized clinical trial, the investigators aim to investigate the impact of intravenous (IV) Clonidine administered at the end of surgery, on the incidence and degree of postoperative agitation. Children will be assigned to either the intervention or the placebo group. The allocation will be carried out centrally and stratified based on age and trial-site, with152 patients allocated to each group. In the intervention group, 3 micrograms per kg of IV clonidine is administered approximately 20 minutes before the expected completion of the surgery (as assessed by the surgeon). In the control group; Saline (placebo) is injected in equal quantity during surgery at the same time. The drugs are concealed in identical blinded ampoules.
The primary outcome is postoperative agitation measured on the Watcha scale. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including 30-day follow-up.
Twenty of the patients age 1-2 years and twenty age >2 years, with a peripheral venous access in place, will be allocated to drug assay sampling; enabling a compartmental PK analysis based on age group, using non-linear mixed effects models.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: ClonidineClonidine : injection og 3 micg/kg IV during the operation. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo : injection og equal amount of NaCl IV during the operation. |
Who may qualify
- Ages
- 1 year to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- scheduled for surgery with Sevoflurane as the choice of anesthesia.
Key exclusion criteria (14 listed)
- ASA classification >2
- Premedication with Clonidine
- Ex-premature (born before week 37+0 AND <60 weeks old)
- Intubated before anaesthesia and/or no plans for extubation after anaesthesia.
- Critical illness with haemodynamic instability.
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: catapresanInjection - during surgery | Drug | Intervention |
| PlaceboAlso: NaClInjection - during surgery | Drug | Placebo |
Primary outcome
Postoperative Agitation
Time frame: 1 day
Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated
4 secondary outcomes
Fentanyl and Morphine Requirements
Time frame: Recorded during the stay in the postoperative recovery room
Pain Assessment
Time frame: recovery room - hours
First Administration of Fentanyl or Morphine
Time frame: recovery room
Adverse Events
Time frame: from intervention to discharge from the recovery room
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24727829Pickard A, Davies P, Birnie K, Beringer R. Systematic review and meta-analysis of the effect of intraoperative alpha(2)-adrenergic agonists on postoperative behaviour in children. Br J Anaesth. 2014 Jun;112(6):982-90. doi: 10.1093/bja/aeu093. Epub 2014 Apr 11.
- Derived from this study: PubMed 30169192Ydemann M, Nielsen BN, Henneberg S, Jakobsen JC, Wetterslev J, Lauritsen T, Steen N, Edstrom B, Afshari A; PREVENT AGITATION Research Group. Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018 Jan;2(1):15-24. doi: 10.1016/S2352-4642(17)30127-X. Epub 2017 Nov 2.
- Derived from this study: PubMed 27264945Ydemann M, Nielsen BN, Wetterslev J, Henneberg S, Lauritsen T, Steen N, Edstrom B, Afshari A. Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial. Dan Med J. 2016 Jun;63(6):A5234.
Related trials for Psychomotor Agitation
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 2/3
Safety and Efficacy of EXV-802 and EXV-801 in the Treatment of Agitation in Alzheimer's Disease Dementia
Agitation Associated With Alzheimer's Disease Dementia
RecruitingPhase 3
Nabilone for Agitation Blinded Intervention Trial
Alzheimer Disease, Agitation
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Weighted Blankets for Agitation in Adults in the Intensive Care Unit
Psychomotor Agitation, Critical Illness
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. This study is not recruiting at the moment.
Steen Henneberg, MD, DMSc study director
Copenhagen University Hospital, Rigshospitalet
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clonidine in people with Psychomotor Agitation, run by Copenhagen University Hospital, Rigshospitalet at 3 sites in Denmark.
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 1 inclusion and 14 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: finished, as of the sponsor's last update on 11 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative Agitation (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02361476, which also lists 3 linked publications.
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 11 Feb 2019.