HYPOTOP Trial

The HYPOTOP Trial is a multi-center double-blinded randomized clinical trihypotopal which is led by our group. This study is based on the investigation of the effects of hypothermia on moderate to severe hypoxic ischemic encephalopathy (HIE) in term newborns, which is causing infantile cerebral palsy and mental retardation. In this clinical trial two groups are compared, both subjected to moderate prolonged hypothermia, one receiving topiramate and the other one a placebo. The main objective of the study is to investigate the clinical outcomes of patients treated with hypothermia and topiramate. Furthermore, pharmacodynamics of topiramate and monitoring the concentrations of topiramate in plasma at several time points during treatment are studied. In addition, oxidative stress and damage on the central nervous system are evaluated using biomarkers determined employing LC-MS/MS methods that allow the quantification of the studied biomarkers in a complex samples matrix at very low concentrations. Having access to this pool of clinical and biochemical information opens the doors for an innovative approach based on untarget metabolomics for the dynamic monitoring of the effect of hypothermia with topiramate vs. hypothermia with placebo, which will also be evaluated in the course of this trial.

ALBINO Trial

Another blinded randomized placebo-controlled multicenter trial that our group is involved in is the ALBINO Trial. This trial aims at studying the effect of allopurinol inalbino addition to hypothermia on neurocognitive outcome for hypoxic-ischemic brain injury. Allopurinol is a xanthine oxidase inhibitor and reduces the production of oxygen radicals and brain damage in experimental studies in animals as well as preliminary human studies of ischemia and reperfusion, if administered early after the insult. This trial is funded by the European Union and involves the screening of over 800 newborns with HIE. The primary objective is to evaluate whether in newborns with asphyxia and early clinical signs of HIE, early postnatal allopurinol compared to placebo administered in addition to standard of care reduces the incidence of death or severe neurodevelopmental impairment at 24 months of age. Furthermore brain injury is assessed by magnetic resonance imaging, cerebral ultrasound, amplitude integrated electroencephalogram, full scale multichannel electroencephalogram and a panel of biomarkers of brain injury. In addition, the safety as well as the pharmacokinetics of allopurinol in neonates treated with hypothermia will be studied.