Journal Article

Hypothermia for encephalopathy in low and middle-income countries (HELIX): study protocol for a randomised controlled trial

Prakash, Vinayagam, Chandramohan, Rema, Herberg, Jethro, Lally, Peter J., Thayyil, Sudhin, Bassett, Paul, Oliveira, Vania, Rodrigo, Ranmali, Seeralar, Arasar, Ramji, Siddarth, Shahidullah, Mohammod, Bandya, Prathik, Mondkar, Jayashree, Benkappa, Naveen, Shankaran, Seetha, Mangalabharathi, Sundaram, Manerkar, Swati, Kumaraswami, Kumutha, Swamy, Ravi, Montaldo, Paolo, Kamalaratnam, Chinnathambi, Nair, Mohandas, Chandrasekaran, Mani, Mannan, Mohammod Abdul

2017

Overview

Background Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18–22 months after neonatal encephalopathy, in LMICs. Methods We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1–2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. Discussion Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. Trial registration ClinicalTrials.gov, NCT02387385 . Registered on 27 February 2015.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Analysis / Asia, Western / Babies / Biomedicine / Body Temperature Regulation / Brain Diseases - diagnosis / Brain Diseases - mortality / Brain Diseases - physiopathology / Brain Diseases - therapy / Child Development / Clinical Protocols / Clinical trials / Consciousness / Convulsions & seizures / Cooling / Developing Countries - economics / Disability Evaluation / Encephalopathy / Health Sciences / Heart rate / High income / Hospital Mortality / Humans / Hypothermia / Hypothermia, Induced - adverse effects / Hypothermia, Induced - economics / Hypoxia-Ischemia, Brain - diagnostic imaging / Hypoxia-Ischemia, Brain - mortality / Hypoxia-Ischemia, Brain - physiopathology / Hypoxia-Ischemia, Brain - therapy / Industrialized nations / Infant / Infant Mortality / Infant, Newborn / Infections / Intensive care / Magnetic Resonance Imaging / Magnetic Resonance Spectroscopy / Medicine / Medicine & Public Health / Mortality / Newborn babies / Palliative care / Poverty / Recruitment / Research Design / Respiration / Risk factors / Sepsis / Severity of Illness Index / Signs / Statistics for Life Sciences / Study Protocol / Time Factors / Traumatic brain injury / Treatment Outcome / Ultrasonic imaging