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 | 100000004863 |
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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 relief, opioid-sparring effect, postoperative nausea and vomiting, discharge readiness, postoperative feeding, time of awakening and sedations levels in the postanaesthetic care unit |
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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)Assessment of pain intensity by age-appropriate scale (FLACC 0= no pain, 10= worst pain). The proportion of patients with pain intensity score >3 during stay in the postanaesthetic care unit. 2)The amount of additional opioid needed during stay in the postanaesthetic care unit (calculated as morphine equivalents) for treatment of postoperative pain 3)Postoperative nausea and vomiting: No validated scale for assessment of PONV exists and PONV will be assessed by nausea/vomiting Yes or No. 4)Time from arrival in the postanaesthetic care unit to the time the patient fulfils local discharge criteria (as judged by physician) 5)Assessed as the time point the child is eating in the postanaesthetic care unit 6)Assessed as the time the child is awake. If the child is not awake 2 hours after arrival to the PACU an awakening attempt may be initiated 7)Assessment of alertness by validated scale (the University of Michigan Sedation Scale). Observational 5-point scale ranging from 1(wide awake) to 5(unarousable with deep stimulation) 8)The number of patients experiencing adverse events 9)Prespecified events of clinical interest including: Clinically relevant hypotension, clinically relevant bradycardia, and clinically relevant apnoea 10)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 11)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 proportion of patients with pain intensity score >3 during stay in the postanaesthetic care unit. 2)The amount of additional opioid needed during stay in the postanaesthetic care unit 3)Postoperative nausea and vomiting during stay in the postanaesthetic care unit. 4)Time from arrival in the postanaesthetic care unit to the time the patient fulfils local discharge criteria 5)Assessed as the time point the child is eating in the postanaesthetic care unit 6)Assessed as the time the child is awake. 7)Assessment of sedation by validated scale during stay in the postanaesthetic care unit 8)During the study period 9)During the study period 10)Approximately 24 hour post dosing 11)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 |