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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01471015
Other study ID # 49096
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received November 2, 2011
Last updated May 6, 2015
Start date September 2012
Est. completion date January 2014

Study information

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

Clinical Trial Summary

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.


Recruitment information / eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment


Intervention

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.
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
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

Locations

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

Sponsors (2)

Lead Sponsor Collaborator
University of Utah Thrasher Research Fund

Country where clinical trial is conducted

United States, 

Outcome

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
See also
  Status Clinical Trial Phase
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Completed NCT02683915 - Reno-protective Effect of Brain Cooling in Newborn With Hypoxia
Recruiting NCT01962233 - Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Hypoxic Ischemic Encephalopathy Phase 1
Completed NCT01683383 - California Transport Cooling Trial N/A
Completed NCT01649648 - Autologous Cord Blood Cells for Brain Injury in Term Newborns Phase 1
Completed NCT01481207 - Magnetic Resonance Imaging and Spectroscopy Biomarkers of Neonatal Hypoxic Ischemic Encephalopathy
Withdrawn NCT00993564 - Magnetic Resonance Imaging (MRI) Thermal Imaging of Infants Undergoing Cooling for Hypoxic Ischemic Encephalopathy (HIE) N/A
Completed NCT00945789 - Erythropoietin in Infants With Hypoxic Ischemic Encephalopathy (HIE) Phase 1/Phase 2
Completed NCT00097097 - Neonatal Resuscitation in Zambia Phase 3
Recruiting NCT02621944 - Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia Early Phase 1
Not yet recruiting NCT02605018 - Neuroprotective Effect of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonatal Encephalopathy Phase 1/Phase 2
Withdrawn NCT01128673 - MRI Thermal Imaging of Infants Undergoing Cooling for Hypoxic Ischemic Encephalopathy(HIE) N/A
Completed NCT01732146 - Efficacy of Erythropoietin to Improve Survival and Neurological Outcome in Hypoxic Ischemic Encephalopathy Phase 3
Completed NCT02349672 - Clinical Utility of Serum Biomarkers for the Management of Neonatal Hypoxic Ischemic Encephalopathy (Control Levels)
Completed NCT02826941 - Moderate Hypothermia in Neonatal Hypoxic Ischemic Encephalopathy Phase 2
Active, not recruiting NCT01138176 - Whole Body Cooling Using Phase Changing Material Phase 1/Phase 2
Recruiting NCT02578823 - Targeted Temperature Management After In-Hospital Cardiac Arrest N/A
Terminated NCT01765218 - Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy Phase 1/Phase 2
Completed NCT01241019 - Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia Phase 2
Completed NCT00620711 - Pilot Study of Head Cooling in Preterm Infants With Hypoxic Ischemic Encephalopathy Phase 1