Evaluation of Clonidine Hydrochloride for Prevention of Emergence Agitation Post-Anesthesia in Pediatric Patients Aged ≤1 Year

The primary objective of the study is to evaluate the efficacy of **clonidine** for the prevention of **emergence agitation** in children aged one year or younger following anesthesia. This is clinically relevant as emergence agitation can lead to increased postoperative complications and distress in pediatric patients. Additionally, the study aims to describe the pharmacokinetic parameters of clonidine when administered as a single dose intraoperatively, which is crucial for understanding its behavior and optimizing its use in this vulnerable population.

Secondary objectives include:

• Evaluating the opioid-sparing effect of clonidine, which could reduce the need for opioid analgesics and their associated side effects.
• Assessing postoperative nausea and vomiting, a common and distressing complication that can affect recovery.
• Evaluating a composite safety outcome to ensure the overall safety profile of clonidine in this setting.

The clinical trial involves a total of **50 participants** who are pediatric patients, both male and female, aged between **3 to 12 months**. The study population was selected based on their scheduled requirement for general anesthesia with sevoflurane and opioid, with the option of induction using propofol. Participants are required to have a legally acceptable representative provide written informed consent for the trial. The trial focuses on evaluating the efficacy of clonidine in preventing **emergence agitation** after anesthesia. The participants are considered a vulnerable population due to their young age. No specific lifestyle considerations such as diet or physical activity are mentioned for this trial.

The clinical trial is designed to evaluate the efficacy of **clonidine hydrochloride** in preventing emergence agitation after anaesthesia in paediatric patients aged 3 to 12 months. This is a Phase 4, randomized, double-blind, controlled trial. The trial will compare the effects of clonidine hydrochloride to a placebo, with both administered as a single dose intraoperatively. The trial is expected to run from October 2021 to January 2026, with participant involvement lasting up to one day, corresponding to the maximum treatment period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, scheduled general anaesthesia with sevoflurane and opioid, and informed consent from a legally acceptable representative. The primary endpoint is the incidence of emergence agitation, measured using the Watcha score, while secondary endpoints include the amount of additional opioid required for postoperative pain and the assessment of postoperative nausea and vomiting (PONV).

Follow-up visits will monitor pharmacokinetic parameters, including compartmental clearance, volume of distribution, and half-life. The end-of-study visit will assess the overall outcomes and any adverse events. Participants may be terminated early from the study if they experience clinically relevant hypotension, bradycardia, or apnoea, or if they withdraw consent. The trial aims to provide valuable insights into the pharmacokinetics and efficacy of clonidine hydrochloride in this specific patient population.

The clinical trial involves the administration of two primary treatments. The first treatment is **Sodium Chloride**, which is utilized as a **solution for injection**. This solution is manufactured and filled in glass ampoules, similar to the Catapresan solution for injection. The **sodium chloride** solution is administered via injection, with a maximum daily dose of 2.7 ml. The total dose does not exceed 2.7 ml, and the treatment period is limited to one day. This solution serves as a parenteral fluid and is not a pediatric formulation. The sodium chloride acts as a non-experimental treatment, likely serving as a placebo or comparator in the trial.

The second treatment is **Catapresan**, which contains the active substance **clonidine hydrochloride**. This medication is also provided as a **solution for injection**. The clonidine hydrochloride is administered via injection at a dosage of 150 micrograms per milliliter. The maximum daily and total dose is 3 micrograms per kilogram of body weight, with the treatment period restricted to one day. This medication is not a pediatric formulation and is used to evaluate the efficacy of clonidine for the prevention of emergence agitation in children aged one year or younger. The trial also aims to describe the pharmacokinetic parameters of clonidine when administered as a single dose intraoperatively. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol.

The efficacy of clonidine for the prevention of **emergence agitation** in pediatric patients will be assessed using specific primary and secondary endpoints. The primary endpoints include the measurement of emergence agitation using the Watcha score, where a score greater than 2 during the stay in the postanesthetic care unit indicates significant agitation. Additionally, pharmacokinetic parameters such as compartmental clearance (CL), volume of distribution (V), and half-life (T½) will be estimated.

Secondary endpoints will evaluate the amount of additional opioid required, calculated as morphine equivalents, to manage postoperative pain. The presence of postoperative nausea and vomiting (PONV) will be assessed qualitatively, with vomiting being directly observable and nausea inferred if the child refuses to eat and other causes are excluded. Furthermore, the trial will monitor the proportion of participants experiencing clinically relevant hypotension, bradycardia, and apnoea.