Hypoxic Ischemic Encephalopathy Clinical Trial
— DANCEOfficial title:
Darbe Administration in Newborns Undergoing Cooling for Encephalopathy
Verified date | May 2015 |
Source | University of Utah |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 30 |
Est. completion date | January 2014 |
Est. primary completion date | January 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A to 12 Hours |
Eligibility |
Inclusion Criteria: Infants will be eligible for the DANCE trial if they have a gestational age > 36 weeks by best obstetric estimate, are < 12 hours old and have evidence of moderate-severe acute perinatal HIE. Eligibility will also include criteria presently used in the NICU to initiate hypothermia: 1. < 6 hours after birth 2. History of an acute perinatal event (abruption, cord prolapsed, severe fetal heart rate abnormality) 3. Severe fetal or early (< 1 hour age) neonatal acidosis: arterial pH = 7.0 or a base deficit = 16m mEq/ L 4. If a blood gas is not available or a blood gas at <1 hour of age has a pH between 7.01 and 7.15, or a base deficit is between 10 and 15.9 mEq/L, additional criteria will be required: - acute perinatal event AND - either a 10-min Apgar score = 5 or assisted ventilation initiated at birth and continued for at least 10 minutes. Exclusion Criteria: 1. Major congenital and/or chromosomal abnormalities 2. Prenatal diagnosis of brain abnormality or hydrocephalus 3. Severe growth restriction (< 1800g) 4. Central venous hematocrit > 65%, platelet count > 600,000/dL, and/or neutropenia (ANC < 500 µL) 5. Maternal history of major vascular thrombosis or multiple fetal losses (> 3 spontaneous abortions) 6. ECMO 7. Infant judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of New Mexico | Albuquerque | New Mexico |
United States | Vanderbilt University School of Medicine | Nashville | Tennessee |
United States | McKay Dee Hospital- Intermountain Healthcare | Ogden | Utah |
United States | Primary Children's Hospital | Salt Lake City | Utah |
United States | University of Utah | Salt Lake City | Utah |
United States | Intermountain Medical Center | Sandy | Utah |
United States | University of Washington | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
University of Utah | Thrasher Research Fund |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The Pharmacokinetic Profile of Darbe After the First Dose During Cooling | 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. | For 72 hours after first dose | Yes |
Primary | The Pharmacokinetic Profile of Darbe After the 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. | For 36 hours after second dose | Yes |
Secondary | Number of Participants With Adverse Events. | 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. |
30 days or until hospital discharge | Yes |
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