Project Details

TIME Study: An RCT of Therapeutic Hypothermia for Infants with Mild Encephalopathy in California

Sonia Bonifacio, MD, FAAP

Summary

BACKGROUND: Neonates with mild HIE are at increased risk of neurodevelopmental disabilities that can have a life-long impact. Therapeutic hypothermia (TH), standard of care for moderate-severe HIE, may provide neuroprotection to those with mild HIE but carries risk and has not been systematically tested in this population. Practice creep exists with many centers applying TH in mild HIE, despite the lack of evidence for safety or efficacy. GAPS: What is the best approach for identifying, consenting and randomizing patients with mild HIE; what is the safety profile of TH in mild HIE, are there unintended consequences of treatment; what is the efficacy of TH in the setting of mild HIE. HYPOTHESIS: 1) We will be able to identify neonates with mild HIE and randomize within 6 hours after birth to treatment with TH (33.5°C for 72 hours) or controlled temperature management; 2) TH will be safe in this population but may have secondary consequences related to treatment and hospitalization; 3) TH will be associated with improved early measures of infant development and behavior at 12 months utilizing the Warner Infant Development Evaluation Assessment and Functional Skills (WIDEA-FS) and the Alberta Infant Motor Score (AIMS). METHODS: Multi-center RCT of TH for infants with mild HIE in California. Neonates with mild HIE (N=68) will be randomized by 6 hours after birth to TH or normothermia using targeted temperature management for 72 hours. The WIDEA-FS and AIMS will be performed at 12-14 months of age. RESULTS: Pending IMPACT: The TIME Study will inform the design of an efficacy trial. If successful we will apply for funding to obtain follow-up at 2 years of age and to increase the sample size to properly evaluate efficacy. The TIME study will elucidate the potential safety concerns of treatment. Only once safety and efficacy are known should TH be implemented in this patient population. Website Link: https://clinicaltrials.gov/ct2/show/NCT04176471