NCT03409770

Brief Summary

Phase II randomised control trial of whole body cooling in mild neonatal encephalopathy.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
140

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Oct 2019

Longer than P75 for not_applicable

Geographic Reach
3 countries

8 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 10, 2018

Completed
14 days until next milestone

First Posted

Study publicly available on registry

January 24, 2018

Completed
1.7 years until next milestone

Study Start

First participant enrolled

October 10, 2019

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2024

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 30, 2024

Completed
Last Updated

August 4, 2023

Status Verified

August 1, 2023

Enrollment Period

4.7 years

First QC Date

January 10, 2018

Last Update Submit

August 2, 2023

Conditions

Neonatal EncephalopathyHypothermia NeonatalMagnetic Resonance Spectroscopy

Outcome Measures

Primary Outcomes (1)

  • Thalamic N-acetyl aspartate level

    Feasibility of obtaining Proton MR spectroscopy thalamic N-acetyl aspartate level

    4 to 14 days after birth

Secondary Outcomes (2)

  • Brain injury on conventional MR imaging

    4 to 14 days after birth

  • Hospital stay

    Upto 30 days after birth

Study Arms (3)

Usual care

NO INTERVENTION

Usual care (normothermia) arm

Therapeutic hypothermia - 48 h

EXPERIMENTAL

Whole body cooling (33 to 34 C) for 48 hours

Other: Therapeutic hypothermia

Therapeutic hypothermia - 72 h

EXPERIMENTAL

Whole body cooling (33 to 34 C) for 72 hours

Other: Therapeutic hypothermia

Interventions

Therapeutic hypothermiaOTHER

Whole body cooling using a servo controlled device

Therapeutic hypothermia - 48 hTherapeutic hypothermia - 72 h

Eligibility Criteria

AgeUp to 6 Hours
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • All of the following three criteria should be met:
  • Age less than six hours. AND
  • Evidence of acute perinatal asphyxia
  • Metabolic acidosis (pH \<7.0 and/or BE \>-16) in cord gas or a blood gas within one of birth.
  • If the pH or BE is borderline (pH\<7.15 to 7.0) and/or BE \>-10 to -16) in cord and/or blood gas within 1h of birth additional evidence of perinatal asphyxia is required, which includes either an acute obstetric event (e.g. cord prolapse, abruption, shoulder dystocia) OR Need for continued resuscitation or ventilation at 10 minutes and/or a 10 min Apgar score \<6
  • Evidence of mild NE (at-least two abnormalities) on an NICHD neurological examination performed between 1 and 6h of birth.

You may not qualify if:

  • The following group of babies will be excluded prior to randomisation
  • Babies without encephalopathy
  • Babies with moderate or severe encephalopathy who meet the current NICE/AAP guidelines for cooling therapy.
  • Babies with seizures (clinical and/or aEEG/EEG)
  • Babies with moderate or severe abnormalities on aEEG voltage criteria.
  • Babies with life threatening congenital malformations

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Wayne State University

Michigan Center, Michigan, 48202, United States

Location

Luigi Vanvitelli Hospital

Naples, Italy

Location

Birmingham Womens Hospital

Birmingham, United Kingdom

Location

Medway NHS Foundation Trust

Gillingham, United Kingdom

Location

Liverpool Womens Hospital

Liverpool, United Kingdom

Location

Homerton University Hospital

London, United Kingdom

Location

Imperial College London

London, United Kingdom

Location

The Newcastle Upon Tyne NHS Foundation Trust

Newcastle, United Kingdom

Location

Related Publications (8)

  • Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.

    PMID: 29095433BACKGROUND

  • Oliveira V, Singhvi DP, Montaldo P, Lally PJ, Mendoza J, Manerkar S, Shankaran S, Thayyil S. Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK. Arch Dis Child Fetal Neonatal Ed. 2018 Jul;103(4):F388-F390. doi: 10.1136/archdischild-2017-313320. Epub 2017 Sep 23.

    PMID: 28942433BACKGROUND

  • Lally PJ, Montaldo P, Oliveira V, Swamy RS, Soe A, Shankaran S, Thayyil S. Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2018 Jul;103(4):F383-F387. doi: 10.1136/archdischild-2017-313321. Epub 2017 Sep 21.

    PMID: 28935718BACKGROUND

  • Lally PJ, Pauliah S, Montaldo P, Chaban B, Oliveira V, Bainbridge A, Soe A, Pattnayak S, Clarke P, Satodia P, Harigopal S, Abernethy LJ, Turner MA, Huertas-Ceballos A, Shankaran S, Thayyil S. Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study. BMJ Open. 2015 Sep 30;5(9):e008912. doi: 10.1136/bmjopen-2015-008912.

    PMID: 26423856BACKGROUND

  • Robertson NJ, Thayyil S, Cady EB, Raivich G. Magnetic resonance spectroscopy biomarkers in term perinatal asphyxial encephalopathy: from neuropathological correlates to future clinical applications. Curr Pediatr Rev. 2014;10(1):37-47. doi: 10.2174/157339631001140408120613.

    PMID: 25055862BACKGROUND

  • Lally PJ, Price DL, Pauliah SS, Bainbridge A, Kurien J, Sivasamy N, Cowan FM, Balraj G, Ayer M, Satheesan K, Ceebi S, Wade A, Swamy R, Padinjattel S, Hutchon B, Vijayakumar M, Nair M, Padinharath K, Zhang H, Cady EB, Shankaran S, Thayyil S. Neonatal encephalopathic cerebral injury in South India assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome. PLoS One. 2014 Feb 5;9(2):e87874. doi: 10.1371/journal.pone.0087874. eCollection 2014.

    PMID: 24505327BACKGROUND

  • Thayyil S, Chandrasekaran M, Taylor A, Bainbridge A, Cady EB, Chong WK, Murad S, Omar RZ, Robertson NJ. Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis. Pediatrics. 2010 Feb;125(2):e382-95. doi: 10.1542/peds.2009-1046. Epub 2010 Jan 18.

    PMID: 20083516BACKGROUND

  • Montaldo P, Cirillo M, Burgod C, Caredda E, Ascione S, Carpentieri M, Puzone S, D'Amico A, Garegrat R, Lanza M, Moreno Morales M, Atreja G, Shivamurthappa V, Kariholu U, Aladangady N, Fleming P, Mathews A, Palanisami B, Windrow J, Harvey K, Soe A, Pattnayak S, Sashikumar P, Harigopal S, Pressler R, Wilson M, De Vita E, Shankaran S, Thayyil S; COMET Trial Group. Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy: A Multicenter Pilot Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e249119. doi: 10.1001/jamanetworkopen.2024.9119.

    PMID: 38709535DERIVED

MeSH Terms

Interventions

Hypothermia, Induced

Intervention Hierarchy (Ancestors)

CryotherapyTherapeutics

Study Officials

  • Sudhin Thayyil, PhD

    Imperial College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
MR spectroscopy analysis will be masked to the allocation
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Therapeutic hypothermia (33 to 34 C) for 2 different durations (48, or 72 h) and usual care (normothermia)
Sponsor Type
INDIV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2018

First Posted

January 24, 2018

Study Start

October 10, 2019

Primary Completion

June 30, 2024

Study Completion

August 30, 2024

Last Updated

August 4, 2023

Record last verified: 2023-08

Data Sharing

IPD Sharing
Will share

Data can be shared unconditionally will be made available when scientific manuscripts are published. Data that cannot be shared publicly (e.g. to protect patient confidentiality) will be by request only. The PI will review each request on case-by-case basis. Upon approval the data requester will be asked to sign a data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
Data will be available 3 to 6 after the end of the study.
Access Criteria
Unidentified data will be shared by publication. Request for data that affects patient confidentiality will review by the study PI on a case-by-case basis.

Locations

GB(6)US(1)IT(1)