E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Agitation after anaesthesia (emergence agitation) is a common complication to anaesthesia in paediatric patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10079742 |
E.1.2 | Term | Agitation on recovery from sedation |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To describe the pharmacokinetic parameters of clonidine when administered as a single dose intraoperatively To evaluate the efficacy of clonidine for prevention of emergence agitation |
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E.2.2 | Secondary objectives of the trial |
To evaluate postoperative pain (opioid-sparring effect), postoperative nausea and vomiting in the postanaesthetic care unit. To evaluate a composite safety outcome of 1) clinically relevant hypotension AND clinically relevant bradycardia, 2) clinically relevant bradycardia AND clinically relevant apnoea. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Paediatric patients, age 3 ≤ 12 months • Scheduled for 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 |
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E.4 | Principal exclusion criteria |
• 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) • Planned for a postoperative nurse-controlled analgesia pump including a continuous infusion of opioid • Bleeding requiring transfusion prior to scheduled anaesthesia • 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic sampling will be conducted to estimate compartmental Clearance (CL), Volume of distribution (V) and T½
Emergence agitation measured on the Watcha score (1= calm, 4= agitated and thrashing around)7. The incidence of emergence agitation (Watcha score >2 during stay in the postanaesthetic care unit). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic end point will be evalutated from dosing to dicharge from the postanaethetic care unit (approx. 0-3 hours post dose)
Emergence agitation measured on the Watcha score (1= calm, 4= agitated and thrashing around)7. The incidence of emergence agitation (Watcha score >2 during stay in the postanaesthetic care unit). |
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E.5.2 | Secondary end point(s) |
1)The amount of additional opioid needed during stay in the postanaesthetic care unit (calculated as morphine equivalents) for treatment of postoperative pain 2)Postoperative nausea and vomiting: No validated scale for assessment of PONV exists and PONV will be assessed by nausea/vomiting Yes or No. 3)Composite safety outcome: The proportion of participants with 1) clinically relevant hypotension and, clinically relevant bradycardia, 2) clinically relevant bradycardia and clinically relevant apnoea. 4)Safety -The number of patients experiencing adverse events -Prespecified events of clinical interest including: Clinically relevant hypotension, clinically relevant bradycardia, and clinically relevant apnoea -24-hour safety follow-up (telephone interview with parents or in-hospital visit, if child is admitted) and an additional 48-hour follow-up for patients with ongoing adverse events at the 24-hour safety follow-up -30-day follow-up in the National Patient Registry to assess any subsequent hospital admissions |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1)The amount of additional opioid needed during stay in the postanaesthetic care unit 2)Postoperative nausea and vomiting during stay in the postanaesthetic care unit. 3)Untill discharge from the postanaesthetic care unit 4) -During the study period -During the study period -Approximately 24 hours post dosing -30 days after dosing |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |