Does Intraoperative Clonidine Reduce Post Operative Agitation in Children?

Study Overview
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Brief Summary
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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
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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.

Official Title
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Does Intraoperative Clonidine Reduce Post Operative Agitation in Children Anaesthetised With Sevoflurane? A RCT Including Pharmacokinetic Investigation.

Conditions
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Psychomotor Agitation

Intervention / Treatment
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* Drug: Clonidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Clonidine : injection og 3 micg/kg IV during the operation. | Drug: Clonidine<br>* Injection - during surgery<br>* Other names: catapresan;|
| Placebo Comparator: Placebo<br>Placebo : injection og equal amount of NaCl IV during the operation. | Drug: Placebo<br>* Injection - during surgery<br>* Other names: NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Agitation | Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fentanyl and Morphine Requirements | Amount used | 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 | recovery room - hours | 
| First Administration of Fentanyl or Morphine | Time to administration | recovery room | 
| Adverse Events |  | from intervention to discharge from the recovery room | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Anaesthesia, Children, Clonidine, Sevoflurane, Postoperative agitation, Prevention, Pharmacokinetics