Study aimed at comparing the impact on long-term neurocognitive development of the use of low dose sevoflurane, dexmedetomidine and remifentanil anaesthesia compared to current anaesthesia with standard dosage of sevoflurane

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Giannina Gaslini Institute For Scientific Hospitalization And Care

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

30 Sep 2020 → ongoing

Decision date (initial)

2024-07-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512385-34-00

EudraCT number

2017-002803-81

ClinicalTrials.gov

NCT03089905

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Determine if, in children less than 2 years of age having anaesthesia expected to last 2 hours or longer, low-dose sevoflurane/dexmedetomidine/remifentanil anaesthesia is superior to standard dose sevoflurane anaesthesia in terms of the global cognitive function as assessed by the full scale IQ score of the Wechsler Preschool and Primary School Intelligence Scale assessed at 3 years of age.

Secondary objectives 1

1. Secondary objectives include determining if, in children less than 2 years of age having anaesthesia expected to last 2 hours or longer, low-dose sevoflurane/dexmedetomidine/remifentanil anaesthesia is superior to standard dose sevoflurane anaesthesia in terms of: a) a range of other neurodevelopmental tests performed at 3 years of age including subscales of general cognitive functioning, language, executive function, memory, adaptive behaviour, clinical behaviour and social skills. b) diagnosis of any neurodevelopment disorder at 3 years of age. c) incidence of intra-operative hypotension, d) intra-operative bradycardia, e) post-operative pain, f) time to recovery, g) PK/PD determination only in patients treated with dexmedetomidine.

Conditions and MedDRA coding

Children under the age of 2 years having surgery lasting at least 2 hours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Younger than 2 years old (chronological age)
2. Scheduled for anaesthesia that is expected to last at least 2 hours (and/or total operating room time is scheduled to be at least 2.5 hours) and for a maximum of 6 hours
3. Type of surgery that can be included, assuming patients do not meet exclusion criteria, are the following: a) Craniofacial (i.e., isolated cleft lip, craniosynostosis, dermoid cysts of the scalp, etc.) b) Thoracic (i.e., isolated lung malformations, diaphragmatic hernia Morgagni type, etc.) c) Abdominal (i.e., Hirschsprung disease, Meckel resection, etc.) d) Urologic (i.e., hypospadias, laparoscopic/robotic hydronephrosis repair, etc.) e) Orthopaedic (i.e., congenital hip dislocation, bilateral congenital clubfoot, etc.) f) Neurosurgical (i.e., isolated spine tethering, brachial plexus repair, etc.)

Exclusion criteria 19

1. Known neurologic, chromosomal or congenital anomaly which is likely to be associated with poor neurobehavioural outcome
2. Existing diagnosis of behavioural or neurodevelopmental disability
3. Prematurity (defined as < 36 weeks gestational age at birth)
4. Birth weight less than 2 kg
5. Congenital cardiac disease requiring surgery
6. Intracranial neurosurgery and intracranial craniofacial surgery (isolated cleft lip is not an exclusion)
7. Previous cumulative exposure to general anaesthesia exceeding 2 hours
8. Planned future cumulative exposure to anaesthesia exceeding 2 hours before the age of 3 years.
9. Any specific contra-indication to any aspect of the protocol.
10. Previous adverse reaction to any anaesthetic
11. Circumstances likely to make long-term follow-up impossible
12. Living in a household where the primary language spoken at home is not a language in which we can administer the Wechsler Preschool and Primary School Intelligence Scale
13. Planned postoperative sedation with any agent except opioids (e.g., benzodiazepines, dexmedetomidine, ketamine, barbiturates, propofol, clonidine, chloral hydrate, and other non-opioid sedatives). For example, if such sedation is planned for post-operative ventilation
14. Known hypersensitivity to the study investigational medicinal products (IMPs) and their excipients
15. Renal impairment, defined as eGFR < 60 mL/min/1.73 m2, as calculated with Schwartz formula (eGFR = 0.5 × height (cm)/plasma creatinine)
16. Hepatic impairment, defined as levels of AST or ALT 3 times above the upper limit of the range of normality, or levels of total bilirubin 2 times above the upper limit of the range
17. Advanced heart block (grade 2 or 3), unless paced
18. Uncontrolled hypotension
19. Acute cerebrovascular conditions

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Full scale IQ score of the Wechsler Preschool and Primary School Intelligence Scale assessed

Secondary endpoints 3

1. Neuropsychological tests • Language (Test TLV - Language evaluation) • Attention/Executive Function/impulse control: (NEPSY-2: Statue Subtest) • Memory: (NEPSY-2: Narrative memory) • Adaptive Behaviour: (Adaptive Behavior Assessment System, 2rd Ed 0-5 years) • Clinical Behaviour: (Child Behavior Checklist for ages 1.5-5 years) • Executive Function: (Behavior Rating of Executive Function- Preschool)
2. Anaesthesia - Incidence of intra-operative hypotension - Intra-operative bradycardia - Post-operative pain (FLACC Scale: Face, Legs, Activity, Cry, Consolability Scale) - Time to recovery
3. Safety - Nature and incidence of adverse events and serious adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Giannina Gaslini Institute For Scientific Hospitalization And Care

Sponsor organisation

Giannina Gaslini Institute For Scientific Hospitalization And Care

Address

Via Gerolamo Gaslini 5

City

Genoa

Postcode

16147

Country

Italy

Scientific contact point

Organisation

Giannina Gaslini Institute For Scientific Hospitalization And Care

Contact name

Nicola Disma

Public contact point

Organisation

Giannina Gaslini Institute For Scientific Hospitalization And Care

Contact name

Anaesthesia Research Group - Murdoch Childrens Research Institute

Third parties 4

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications