Clinical trial NCT02361476: Does Intraoperative Clonidine Reduce Post Operative Agitation in Children?
Official title: Does Intraoperative Clonidine Reduce Post Operative Agitation in Children Anaesthetised With Sevoflurane? A RCT Including Pharmacokinetic Investigation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psychomotor Agitation
Keywords: Anaesthesia
Children
Clonidine
Sevoflurane
Postoperative agitation
Prevention
Pharmacokinetics
Safety
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2015-02-11
Enrollment: 379
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* scheduled for surgery with Sevoflurane as the choice of anesthesia.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Postoperative Agitation
timeFrame: 1 day
Secondary outcomes:
measure: Fentanyl and Morphine Requirements
timeFrame: Recorded during the stay in the postoperative recovery room
measure: Pain Assessment
timeFrame: recovery room - hours
measure: First Administration of Fentanyl or Morphine
timeFrame: recovery room
measure: Adverse Events
timeFrame: from intervention to discharge from the recovery room
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet
state: Zealand
city: Køge
country: Denmark
facility: Køge Sygehus, Anæstesiologisk Afdeling
city: Vejle
country: Denmark
facility: Anæstesiologisk afdeling, Vejle Sygehus
Study officials:
affiliation: Rigshospitalet, Denmark
name: Steen Henneberg, MD, DMSc
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Ydemann 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.
citation: Ydemann 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.