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Darbe Administration in Newborns Undergoing Cooling for Encephalopathy (DANCE)
Selective head cooling or whole body hypothermia has become the standard of care for neonatal hypoxia-ischemia encephalopathy (HIE). Despite early intervention death or major neurodevelopmental disability still occurs in nearly 50% of infants ≥ 36 weeks gestational age (GA) treated with cooling. No additional therapies have proven to be efficacious in further reducing brain injury and impairment for these high risk infants. Neuroprotective strategies aimed at improving early childhood outcomes are still needed. An important area of study includes therapies that may complement the neuroprotective effects of hypothermia and promote neuronal regeneration, recovery and neurovascular remodeling. Among these therapies, erythropoiesis stimulating agents (ESA) have been shown to provide neuroprotection, improving short and long-term neurologic outcome in brain injury and HIE in neonatal and adult animal models. Parallel with neuroprotective effects in experimental settings, recent small clinical studies suggest improved outcomes after ESA administration in patients with severe traumatic brain injury and HIE. ESA may work through several important mechanisms including reduced inflammation, limited oxidative stress, decreased apoptosis and white matter injury, as well as via pro-angiogenic and neurogenic properties. Darbepoetin alfa (Darbe), a recombinant human erythropoietin (EPO)-derived molecule, has an extended circulating half life and comparable biological activity to EPO, including activation of the EPO receptor. The proposed study is a Phase I/II dose safety and pharmacokinetic trial of early Darbe administered concurrent with hypothermia in human newborn infants with moderate to severe birth asphyxia. The long-term objectives of the proposed research are to reduce mortality and to decrease the risk of long-term disabilities in infants with HIE who survive beyond the newborn period.
Details
| Lead sponsor | University of Utah |
|---|---|
| Phase | Phase 1/Phase 2 |
| Status | COMPLETED |
| Enrolment | 30 |
| Start date | 2012-09 |
| Completion | 2014-01 |
Conditions
- Hypoxic Ischemic Encephalopathy
Interventions
- Darbepoetin alfa
- Darbepoetin alfa
- Placebo
Primary outcomes
- The Pharmacokinetic Profile of Darbe After the First Dose During Cooling — For 72 hours after first dose
The pharmacokinetic profile of Darbe wil be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. Serum levels will be drawn at 4,12, 18, 24, 36, 60, and 72 hours post initial dose. Area under the plasma concentration versus time curve (AUC) will be used. - The Pharmacokinetic Profile of Darbe After the Second Dose. — For 36 hours after second dose
The pharmacokinetic profile of Darbe will be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. A second dose of Darbe will be given at 7 days of age, and serum drug levels will be obtained at 12, 18, 24, and 36 hours post second dose. Area under the plasma concentration versus time curve (AUC) will be used.
Countries
United States