Darbe Administration in Newborns Undergoing Cooling for Encephalopathy (DANCE)
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|ClinicalTrials.gov Identifier: NCT01471015|
Recruitment Status : Completed
First Posted : November 11, 2011
Results First Posted : May 22, 2015
Last Update Posted : May 22, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Hypoxic Ischemic Encephalopathy||Drug: Darbepoetin alfa Drug: Placebo||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Darbe Administration in Newborns Undergoing Cooling for Encephalopathy|
|Study Start Date :||September 2012|
|Actual Primary Completion Date :||January 2014|
|Actual Study Completion Date :||January 2014|
Active Comparator: High dose Darbepoetin alfa
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Drug: Darbepoetin alfa
10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
Active Comparator: Low dose Darbepoetin alfa
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Drug: Darbepoetin alfa
2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
Placebo Comparator: Placebo
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
- The Pharmacokinetic Profile of Darbe After the First Dose During Cooling [ Time Frame: 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. [ Time Frame: 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.
- Number of Participants With Adverse Events. [ Time Frame: 30 days or until hospital discharge ]
Potential adverse events such as (but not limited to) alterations in blood pressure, secondary infections, neutropenia, thrombotic/vascular events, hematologic events (platelets, Hct level, polycythemia), and hepatic/renal function that are outside of normal range for the study population.
Complications associated with HIE or cooling therapy will not be considered an AE for this study. AEs reported to be associated with cooling include: bleeding/thrombosis, persistent pulmonary hypertension of the newborn (PPHN), skin changes, arrhythmia, and persistent acidosis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01471015
|United States, New Mexico|
|University of New Mexico|
|Albuquerque, New Mexico, United States, 87131-0001|
|United States, Tennessee|
|Vanderbilt University School of Medicine|
|Nashville, Tennessee, United States, 37232-9544|
|United States, Utah|
|McKay Dee Hospital- Intermountain Healthcare|
|Ogden, Utah, United States, 84403|
|University of Utah|
|Salt Lake City, Utah, United States, 84108|
|Primary Children's Hospital|
|Salt Lake City, Utah, United States, 84132|
|Intermountain Medical Center|
|Sandy, Utah, United States, 841074|
|United States, Washington|
|University of Washington|
|Seattle, Washington, United States, 98195-6320|
|Principal Investigator:||Mariana Baserga, MD||University of Utah|