Darbe Administration in Newborns Undergoing Cooling for Encephalopathy

NCT ID: NCT01471015

Last Updated: 2024-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2014-01-31

Brief 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.

Conditions

Hypoxic Ischemic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Darbepoetin alfa

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Darbepoetin alfa

Intervention Type: DRUG

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 doses, with the first given within 12 hours of delivery and the second given at 7 days old

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Mariana Baserga

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mariana Baserga, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

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

University of Utah

Salt Lake City, Utah, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Intermountain Medical Center

Sandy City, Utah, United States

University of Washington

Seattle, Washington, United States

Countries

United States

Other Identifiers

49096

Identifier Type: -

Identifier Source: org_study_id