E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children undergoing general anaesthesia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021723 |
E.1.2 | Term | Induction and maintenance of anaesthesia |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Recent research by Munoz et al and Jeleazcov et al have delineated the 'Keo' time constant which describes the transition of propofol from the blood, where it is delivered by infusion, to the brain where the desired clinical effects ie. anaesthesia are seen. In particular, the research by Jeleazcov describes the fact that the speed of this transition varies between infants and older children. We wish to use the age-dependent Keo value to produce an infusion schedule which allows targeting of effect-site concentrations of propofol in a paediatric population.
The primary research question is to assess the performance of this model in clinical practice, which will be done using the four standard parameters described by Varvel et al. A performance error is calculated from the concentration of propofol measured in whole blood (Cmeas), and the concentration predicted by the software (Cpred). From this, the four standard measures of bias, precision, divergence and wobble are drived. These |
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E.2.2 | Secondary objectives of the trial |
• Population pharmacokinetics of propofol in children aged 1 to 12 years using non-linear effects modelling (NONMEM). Pharmacokinetics described the way the body handles the drug in terms of the effective volume the drug is dissolved in, and the rate at which the drug is removed from the body (volume of distribution and clearance respectively. The relationships between these pharmacokinetic parameters and the variables of age, gender and weight can be explored. • Pharmacodynamic modelling, using bispectral index as a measure of depth of anaesthesia. Pharmacodynamics describe the relationship between doses used, and the clinical effects which are observed. Bis is an EEG-derived measure of the depth of anaesthesia, which is measured from an adhesive strip placed across the forehead. This will allow direct estimation of the blood-brain equilibration rate-constant (keo) for propofol in this patient population. • Establish a safety profile for effect-site TCI propofol based on the pharm |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
ASA 1 and 2 healthy male and female children aged 1 to 12 years (inclusive) Weight 6 – 60 kg Elective surgery suitable for general anaesthesia with regional blockade, for example herniotomy, ligation of patent processus vaginalis, testicular fixation and hypospadias repair, or minimally stimulating procedures not requiring opiate supplementation, such as endoscopy and radiological investigation or intervention. Surgery or procedure of expected duration of at least 30 minutes Written parental consent, or child’s consent if competent, for inclusion Child appropriate for intravenous induction and maintenance of anaesthesia with propofol Agreement to undergo intravenous induction of anaesthesia No contraindication to application of topical local anaesthesia prior to cannulation |
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E.4 | Principal exclusion criteria |
• Parental refusal, or refusal of child if competent • Allergy to propofol, or any constituent of propofol • Sensitivity to adhesive agents, as used in the BIS measurement strip • Refusal of intravenous induction • Need for sedative premedication • Inadequate topical analgesia for intravenous cannulation • Inability to site intravenous cannula within two attempts
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E.5 End points |
E.5.1 | Primary end point(s) |
• Performance of an effect-site TCI pharmacokinetic model for children aged 1 to 12 years, and weight 6 – 60kg, as calculated from the four standard parameters described by Varvel et al. The performance error (PE) is calculated from the concentration of propofol measured in whole blood (Cmeas) and the concentration predicted by the software (Cpred) as follows: PE(%) = ((Cmeas-Cpred)/Cpred)x100. Four standard measures of performance are derived from this value, namely bias, precision, divergence and wobble.o,p These derived parameters estimate quantitatively whether the system over- or under-delivers propofol, and how this varies both between patients and for an individual patient over time. |
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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 | No |
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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
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 | Information not present in EudraCT |
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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Discharge of the last patient after completion of anaesthesia, surgery and routine postoperative care. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 30 |