E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inguinal hernia in neonates and infants |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022016 |
E.1.2 | Term | Inguinal hernia |
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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 |
The primary objective of this trial is to determine whether different types of anaesthesia [regional versus general] given to infants undergoing inguinal hernia repair result in equivalent neurodevelopmental outcomes. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to describe the frequency and characteristics of apnoea in the post-operative period after both regional and general anaesthesia for inguinal hernia repair in infants, and determine the factors associated with apnoea. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Any child scheduled for unilateral or bilateral inguinal hernia repair (with or without circumcision). |
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E.4 | Principal exclusion criteria |
• Any child older than 60 weeks post menstrual age • Any child born at less than 26 weeks gestation • Any contraindication to general or spinal/caudal anaesthesia (for example: neuromuscular disorder or coagulopathy) • Pre-operative ventilation immediately prior to surgery • Congenital heart disease that has required surgery or will require surgery or which requires ongoing pharmacotherapy • Known chromosomal abnormality or any other known acquired or congenital abnormalities (apart from prematurity) which are likely to affect development • Children where follow-up would be difficult for geographic or social reasons • Families where the primary language spoken at home is not the language in which the WPSI-III will be given [i.e. English for Australian sites, French for Paris site and English or Spanish for US sites] • Known neurological injury such as cystic periventricular leukomalacia (PVL), or grade 3 or 4 intra ventricular haemorrhage (IVH) (+/- post haemorrhage ventricular dilatation) • Previous exposure to volatile anaesthesia or benzodiazepines as a neonate or in the third trimester in utero
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E.5 End points |
E.5.1 | Primary end point(s) |
6.1 Primary outcome
The primary outcome will be the WPPSI-III Full Scale IQ score at 5 years corrected age.
6. 2 Secondary outcomes
Secondary outcomes fall into four areas: 1) Other measures of neurodevelopmental outcome 2) Incidence of apnoea 3) Other outcomes relating to anaesthesia group 4) Incidental outcomes not related to choice of anaesthesia
6.2.1 Other measures of neurodevelopmental outcome
6.2.1.1 Neurodevelopmental secondary outcomes at 2 years: • Cognitive, motor and language scales of the Bayley Scales of Infant Development III [Bayley 2005]. • A paediatric assessment including a neurological examination to determine the presence of cerebral palsy will be conducted by a paediatrician blinded to the type of anaesthetic used. • Data regarding visual and hearing acuity will be collected, or where not previously conducted, visual and audiology assessments will be arranged. • Some sites will perform the experimental Delayed Alternation and Spatial Reversal tasks (Espy)
6.2.1.2 School age developmental outcome at 5 years: • A paediatric assessment as per 2 years. • General intellectual ability, verbal, visuo-spatial and processing speed skills are incorporated into the Wechsler Preschool and Primary Scale of Intelligence - Third Edition (WPPSI-III) The primary outcome is the full scale, while subscales will be computed as secondary outcomes. • Auditory and visual attention will be assessed using the NEPSY tasks. • The behaviour features of executive dysfunction will be assessed via the Behavioural Rating of Executive Function (BRIEF).
6.2.2 Apnoea
Apnoea will be defined in terms of changes in recorded vital signs and need for intervention. The timing of the apnoea will also be early or late.
6.2.2.1 Significant apnoea by vital signs
A significant apnoea will be defined as a pause in breathing of greater than 15 seconds or a pause greater than 10 seconds if associated with oxygen saturation <80% or bradycardia (20% fall in heart rate).
6.2.2.2 Significant apnoea by intervention
Any intervention for apnoea will be recorded as frequency, time and nature of intervention. Types of intervention recorded will include need for stimulation, assisted ventilation, CPAP, endo-tracheal intubation administration of a methylxanthine stimulant, delay in discharge home due to apnoea or discharge from hospital with a home apnoea monitor.
6.2.2.3 Early apnoea
Any significant apnoea in the PACU or the first 30 minutes of the NICU if PACU is bypassed or in the operating room after completion of surgery, discontinuation of general anaesthesia and removal of laryngeal mask or endo-tracheal tube.
6.2.2.4 Late apnoea
Any documented significant apnoea occurring in NICU or other hospital ward within 24 hours of completion of surgery, excluding early apnoeas
6.2.3 Other outcomes relating to anaesthesia group: • Success rate of nerve block • Time taken for nerve block • Behaviour of child during nerve block, during surgery and in PACU • Time to first feeding
6.2.4. Incidental outcomes not related to choice of anaesthesia: • Incidence of hernia recurrence at 2 years will be recorded. If the repair was unilateral the incidence of contralateral occurrence will be noted.
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Developmental assessment of the last child recruited at 5 year follow up |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |