Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia

NCT ID: NCT00934700

Last Updated: 2022-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-09-30

Brief Summary

This is a randomised controlled trial in newborn infants with perinatal asphyxial encephalopathy assessing whether a combination of hypothermia and inhaled xenon preserve cerebral metabolism and structure.

Detailed Description

The study hypothesis is that: Following perinatal asphyxia treatment with a combination of hypothermia and inhaled xenon preserves cerebral metabolism and structure. Following informed parental consent, infants that continue to require endotracheal tube ventilation following resuscitation will be randomised to treatment with hypothermia only or hypothermia and xenon. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants allocated to hypothermia and xenon will also receive 30% xenon (balanced with oxygen and air) for 24 hours through a purpose designed delivery system. Structured neurological examination will be done daily during the 1st week after birth and at discharge. MRS and MRI will be performed once between 4-10 days of age. MRS/MRI data analysis will be by investigators blinded to the allocated intervention.

Conditions

Hypoxic Ischaemic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Combination of hypothermia and xenon

Combination of hypothermia and inhaled xenon

Group Type: EXPERIMENTAL

Xenon gas

Intervention Type: OTHER

30% Xenon gas inhaled for 24 hours

Hypothermia and standard intensive care

Hypothermia and standard intensive care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Xenon gas

30% Xenon gas inhaled for 24 hours

Intervention Type: OTHER

Other Intervention Names

LENOXe

Eligibility Criteria

Inclusion Criteria

Infants will be eligible for enrolment into the trial if each of the following criteria is fulfilled:

• Infants 36 to 43 weeks gestation with at least one of the following:

• Apgar score of <5 at 10 minutes after birth;
• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth;
• Acidosis defined as pH <7.00 and/or base deficit >15 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood).
• Moderate to severe encephalopathy consisting of altered state of consciousness (reduced or absent response to stimulation) and hypotonia, and abnormal primitive reflexes (weak or absent suck or Moro response). Clinical severity of HIE will be assessed by Thompson encephalopathy score, and modified Sarnat score.
• At least 30 minutes duration of amplitude integrated EEG (aEEG) recording that shows moderately abnormal or suppressed background aEEG activity or seizures

Exclusion Criteria

• If treatment with hypothermia is delayed beyond 6 hours, or infants are expected to be >12 hours of age at the time of randomisation; Infants with ventilatory oxygen requirement > 70%; Attending clinician considers infant not suitable to participate because of other serious congenital abnormalities, or the infant's condition appears terminal.

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 12 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College London Hospitals

OTHER

Sponsor Role: collaborator

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis Azzopardi, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial College Academic Healthcare Trust

London, , United Kingdom

Countries

United Kingdom

References

Azzopardi D, Robertson NJ, Bainbridge A, Cady E, Charles-Edwards G, Deierl A, Fagiolo G, Franks NP, Griffiths J, Hajnal J, Juszczak E, Kapetanakis B, Linsell L, Maze M, Omar O, Strohm B, Tusor N, Edwards AD. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. Lancet Neurol. 2016 Feb;15(2):145-153. doi: 10.1016/S1474-4422(15)00347-6. Epub 2015 Dec 19.

Reference Type: RESULT

PMID: 26708675 (View on PubMed)

Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008.

Reference Type: DERIVED

PMID: 24524452 (View on PubMed)

Other Identifiers

prot-002-2009

Identifier Type: -

Identifier Source: org_study_id