Table 1.
Summary of the 14 pilot trials and two clinical trials (phase III)* of therapeutic hypothermia from low and middle-income countries [[66], [67]].
| Author, Year | Country | Cooling method | Number: cooled/control | Primary Outcome | Mortality: cooled/control | Neurodisability at 18 months or more | Result |
|---|---|---|---|---|---|---|---|
| Akisu, 2003 | Turkey | Cooling head cap | 11/10 | Abnormal EEG and reduction in CSF platelet activating factor (PAF) levels. | 0/2 | Not available | Only significant reduction found in abnormal EEG. Reduction in CSF – PAF in cooled babies. |
| Bhat, 2006 | India | Unknown device | 20/15 | Death/abnormal neuro exam at discharge | 3/5 | Not available | No difference in mortality, lesser abnormal neuro exam in cooled group |
| Lin, 2006 | China | Cooling head cap | 32/30 | Neonatal behavioural neuro assessment (NBNA) at 7–10 days/Brain injury on CT scan | 2/2 | Not available | Improvement in injury on CT scans and NBNA |
| Robertson, 2008 | Uganda | Water bottles | 21/15 | Death/seizures/abnormal neuro exam | 7/1 | Not available | Higher mortality in cooled group |
| Zhou, 2010* | China | Cooling head cap | 100/94 | Death/severe disability at 18 months | 20/27 | Yes | Lesser death/severe disability in cooled group |
| Bharadwaj, 2012 | India | Gel packs | 62/62 | Death/Developmental delay at 6 months | 3/6 | Not available | No difference in mortality |
| Joy, 2012 | India | Gel packs | 58/58 | Oxidative stress | 1/4 | Not available | Lesser oxidative stress in cooled group |
| El Shimi, 2013 | Egypt | Gel packs | 10/10 | Brain-derived neurotrophic factor (BDNF) and Neuron Specific Enolase (NSE), MRI brain | 4/8 | Not available. | Mortality, MRI score lower in cooled group. |
| Gane, 2013 | India | Gel packs | 60/60 | 8-hydroxy2-deoxyguanosine levels | 4/8 | Not available. | Lower 8-hydroxy2-deoxyguanosine levels in cooled group |
| Thayyil, 2013 | India | Phase change material | 17/16 | MRI imaging biomarkers | 4/2 | Not available | Higher mortality in cooled; no reduction in whole brain fractional anisotropy on tract based spatial statistics with cooling |
| Thanigasalam, 2015 | India | Gel packs | 60/60 | Acute kidney injury | 16/30 | Not available | Cooling reduced acute kidney injury |
| Rakesh K, 2017 | India | Phase change material | 60/60 | Myocardial dysfunction | 9/16 | Not available | Reduced myocardial dysfunction in cooled group |
| Chen, 2018 | China | Cooling head cap | 18/18 | Death/Severe disability at 15 months | 0/1 | Not available | No difference in primary outcome |
| Aker 2019 (THIN study) | India | Phase change material | 11/11 | Magnetic resonance imaging (MRI) | 2/1 | Not available | Seriously underpowered study to make any valid scientific conclusions. |
| Catherine, 2020 | India | Phase change material | 76/79 | Death/Neurodisability at discharge and at 18 months of age | 22/29 | Yes | No difference in primary outcome |
| Thayyil, 2021 (HELIX trial)* | India, Sri Lanka, Bangladesh | Tecotherm Neo | 202/206 | Death/Neurodisability at discharge and at 18 months of age | 84/63 | Yes | No difference in primary outcome; significant increase in mortality |