Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial.

OBJECTIVE

To evaluate the neuroprotective effect of therapeutic hypothermia (TH) induced by phase changing material (PCM) on MRI biomarkers in infants with hypoxic-ischaemic encephalopathy (HIE) in a low-resource setting.

DESIGN

Open-label randomised controlled trial.

SETTING

One neonatal intensive care unit in a tertiary care centre in India.

PATIENTS

50 term/near-term infants admitted within 5 hours after birth with predefined physiological criteria and signs of moderate/severe HIE.

INTERVENTIONS

Standard care (n=25) or standard care plus 72 hours of hypothermia (33.5°C±0.5°C, n=25) induced by PCM.

MAIN OUTCOME MEASURES

Primary outcome was fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC) on neonatal diffusion tensor imaging analysed according to intention to treat.

RESULTS

Primary outcome was available for 22 infants (44%, 11 in each group). Diffusion tensor imaging showed significantly higher FA in the cooled than the non-cooled infants in left PLIC and several white matter tracts. After adjusting for sex, birth weight and gestational age, the mean difference in PLIC FA between groups was 0.026 (95% CI 0.004 to 0.048, p=0.023). Conventional MRI was available for 46 infants and demonstrated significantly less moderate/severe abnormalities in the cooled (n=2, 9%) than in the non-cooled (n=10, 43%) infants. There was no difference in adverse events between groups.

CONCLUSIONS

This study confirmed that TH induced by PCM reduced brain injury detected on MRI in infants with moderate HIE in a neonatal intensive care unit in India. Future research should focus on optimal supportive treatment during hypothermia rather than looking at efficacy of TH in low-resource settings.

TRIAL REGISTRATION NUMBER

CTRI/2013/05/003693.