Hypothermia for Encephalopathy in Low and Middle-Income Countries Trial

NCT02387385 | Completed DMC

• 1 other identifier: 15HH
• Study Type: interventional
• Target: 408
• Locations: 3 countries
• Sites: 9

Brief Summary

Neonatal Encephalopathy is a serious condition arising from unexpected lack of cerebral blood flow and oxygen supply to the foetal brain at the time of birth. Every year, approximately one million babies die from neonatal encephalopathy in low and middle-income countries and a quarter of these deaths occur in India. In the past decade, a number of clinical trials in high-income countries has shown that cooling therapy along with optimal neonatal intensive care reduces death and neurodisability after neonatal encephalopathy. Cooling therapy is now used as a standard therapy after neonatal encephalopathy in all high income countries, including the UK. Although the burden of neonatal encephalopathy is far higher in low and middle-income countries, the safety and efficacy data on cooling therapy from high income cooling trials cannot be extrapolated to these settings, due to the difference in population co-morbidities and sub-optimal neonatal intensive care. The HELIX trial proposes to examine whether whole body cooling to 33.5°C initiated within 6 hours of birth and continued for 72 hours reduces death or neurodisability at 18 months after neonatal encephalopathy in public sector neonatal units in India. A total of 408 babies with moderate or severe neonatal encephalopathy will be recruited from the participating centres in India over an 18 to 24 month period. The babies will be randomly allocated to whole body cooling or usual care. The cooling therapy will be achieved using an approved cooling device (Tecotherm) that is already in clinical use in the UK and in India. MR imaging and spectroscopy will be performed at 1 week of age to examine the brain injury. Neurodevelopmental outcomes will be assessed at 18 months of age. Primary outcome measure is death or moderate/severe neurodisability at 18 months.

Conditions

Neonatal Encephalopathy

Outcome Measures

Primary Outcomes (1)

• Composite outcome of Death or moderate or severe neurodisability

  18 to 22 months

Secondary Outcomes (18)

• Mortality from any cause

  before discharge from hospital Expected average of 3 weeks

• Major intracranial haemorrhage

  before discharge from hospital Expected average of 3 weeks

• Gastric bleeds (fresh blood > 5 ml from nasogastric tube)

  before discharge from hospital Expected average of 3 weeks

• Persistent hypotension (mean blood pressure < 40 mm of Hg requiring inotropic support)

  before discharge from hospital Expected average of 3 weeks

• Pulmonary haemorrhage (Copious bloody secretions with clinical deterioration requiring change(s) in ventilatory management)

  before discharge from hospital Expected average of 3 weeks

Study Arms (2)

Intervention

ACTIVE COMPARATOR

Whole body cooling to 33 degrees C to 34 degrees C

Device: Whole body cooling (Tecotherm)

Standard of Care

NO INTERVENTION

Standard of care

Interventions

Whole body cooling (Tecotherm) DEVICE

Whole body cooling to 33 to 34 C using Tecotherm

Intervention

Eligibility Criteria

• Age: Up to 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age \< 6 hours, Birth-weight \>1.8 kg, Gestation \>36 weeks
• Need for continued resuscitation at 5 minutes after birth and/or 5 minute Apgar score \<6 (in babies born at hospital) or lack of cry by 5 minutes of age (for babies born at home)
• Evidence of moderate or severe encephalopathy on clinical examination within 6 hours of age.

You may not qualify if:

• Absent heart rate at 10 minute of age despite adequate resuscitation.
• Major life threatening congenital malformation.
• Migrant family or parents unable/unlikely to come back for follow up at 18 months.
• Lack of parental consent.

Sponsors & Collaborators

• Thayyil, Sudhin: lead
• Madras Medical College: collaborator
• Indira Gandhi Medical College, Shimla: collaborator
• Lokmanya Tilak Municipal Medical College and Hospital: collaborator
• Imperial College London: collaborator
• Maulana Azad Medical College: collaborator
• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: collaborator
• University of Kelaniya: collaborator
• Medical College Trivandrum: collaborator

Study Sites (9)

Bangabandhu Sheikh Mujib Medical University

Dhaka, 1000, Bangladesh

Location

Institute of Obstetrics and Gynaecology

Chennai, Tamil Nadu, India

Location

Indira Gandhi Institute of Child Health

Bangalore, India

Location

Calicut Medical College

Calicut, India

Location

Institute of Child Health, Madras Medical College

Chennai, India

Location

Sion Hospital

Mumbai, India

Location

Maulana Azad Medical College

New Delhi, India

Location

Medical College Trivandrum

Trivandrum, India

Location

University of Kelaniya

Kelaniya, Sri Lanka

Location

Related Publications (5)

• Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil S. Cooling in a low-resource environment: lost in translation. Semin Fetal Neonatal Med. 2015 Apr;20(2):72-9. doi: 10.1016/j.siny.2014.10.004. Epub 2014 Oct 31.

  PMID: 25457083 BACKGROUND

• Thayyil S, Oliveira V, Lally PJ, Swamy R, Bassett P, Chandrasekaran M, Mondkar J, Mangalabharathi S, Benkappa N, Seeralar A, Shahidullah M, Montaldo P, Herberg J, Manerkar S, Kumaraswami K, Kamalaratnam C, Prakash V, Chandramohan R, Bandya P, Mannan MA, Rodrigo R, Nair M, Ramji S, Shankaran S; HELIX Trial group. Hypothermia for encephalopathy in low and middle-income countries (HELIX): study protocol for a randomised controlled trial. Trials. 2017 Sep 18;18(1):432. doi: 10.1186/s13063-017-2165-3.

  PMID: 28923118 RESULT

• Thayyil S, Pant S, Montaldo P, Shukla D, Oliveira V, Ivain P, Bassett P, Swamy R, Mendoza J, Moreno-Morales M, Lally PJ, Benakappa N, Bandiya P, Shivarudhrappa I, Somanna J, Kantharajanna UB, Rajvanshi A, Krishnappa S, Joby PK, Jayaraman K, Chandramohan R, Kamalarathnam CN, Sebastian M, Tamilselvam IA, Rajendran UD, Soundrarajan R, Kumar V, Sudarsanan H, Vadakepat P, Gopalan K, Sundaram M, Seeralar A, Vinayagam P, Sajjid M, Baburaj M, Murugan KD, Sathyanathan BP, Kumaran ES, Mondkar J, Manerkar S, Joshi AR, Dewang K, Bhisikar SM, Kalamdani P, Bichkar V, Patra S, Jiwnani K, Shahidullah M, Moni SC, Jahan I, Mannan MA, Dey SK, Nahar MN, Islam MN, Shabuj KH, Rodrigo R, Sumanasena S, Abayabandara-Herath T, Chathurangika GK, Wanigasinghe J, Sujatha R, Saraswathy S, Rahul A, Radha SJ, Sarojam MK, Krishnan V, Nair MK, Devadas S, Chandriah S, Venkateswaran H, Burgod C, Chandrasekaran M, Atreja G, Muraleedharan P, Herberg JA, Kling Chong WK, Sebire NJ, Pressler R, Ramji S, Shankaran S; HELIX consortium. Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh. Lancet Glob Health. 2021 Sep;9(9):e1273-e1285. doi: 10.1016/S2214-109X(21)00264-3. Epub 2021 Aug 3.

  PMID: 34358491 RESULT

• Pant S, Elias MA, Woolfall K, Morales MM, Lincy B, Jahan I, Sumanasena SP, Ramji S, Shankaran S, Thayyil S; HELIX Trial consortium investigators. Parental and professional perceptions of informed consent and participation in a time-critical neonatal trial: a mixed-methods study in India, Sri Lanka and Bangladesh. BMJ Glob Health. 2021 May;6(5):e005757. doi: 10.1136/bmjgh-2021-005757.

  PMID: 34020995 RESULT

• Thayyil S, Montaldo P, Krishnan V, Ivain P, Pant S, Lally PJ, Bandiya P, Benkappa N, Kamalaratnam CN, Chandramohan R, Manerkar S, Mondkar J, Jahan I, Moni SC, Shahidullah M, Rodrigo R, Sumanasena S, Sujatha R, Burgod C, Garegrat R, Mazlan M, Chettri I, Babu Peter S, Joshi AR, Swamy R, Chong K, Pressler RR, Bassett P, Shankaran S. Whole-Body Hypothermia, Cerebral Magnetic Resonance Biomarkers, and Outcomes in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy Born at Tertiary Care Centers vs Other Facilities: A Nested Study Within a Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2312152. doi: 10.1001/jamanetworkopen.2023.12152.

  PMID: 37155168 DERIVED

Study Officials

• Sudhin Thayyil, PhD

  Imperial College London

  STUDY DIRECTOR

• Vania Oliveira, MSc

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Seetha Shankaran, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 13, 2015
• Study Start: August 1, 2015
• Primary Completion: September 30, 2020
• Study Completion: December 1, 2020
• Last Updated: May 27, 2022

Record last verified: 2022-05

Locations

BA (1); SR (1); IN (7)