Mild Encephalopathy in the Newborn Treated With Darbepoetin

NCT ID: NCT03071861

Last Updated: 2023-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2022-09-01

Brief Summary

This is a Phase II multicenter placebo-controlled randomized, feasibility/safety trial. Infants >34 week gestational age with perinatal acidemia and mild neonatal encephalopathy on the modified Sarnat neurologic examination at less than six hours of age. Participants will be randomized to receive either one dose of Darbepoetin, or placebo within 24 hours of birth. Neurodevelopmental testing (Bayley (III or IV) and Gross Motor Function Assessment) will be performed at 24 months of age. Pharmacokinetics will be assessed on those infants that received Darbe.

Detailed Description

Therapeutic hypothermia (TH) is the standard of care for newborns diagnosed with moderate to severe neonatal encephalopathy (NE) presumably due to hypoxic ischemia. In order to be eligible for TH an infant must have perinatal acidemia and evidence of moderate or severe encephalopathy on a standardized neurologic examination (Sarnat). However, the majority of newborns with perinatal acidemia do not have a neurologic examination abnormal enough to be classified as moderate or severe NE. In a retrospective review, DuPont et al. found that as many as 20% of newborns with perinatal academia and mild NE have abnormal short-term outcomes such as seizures, death from progressive asphyxia insult, brain MRI findings consistent with NE, abnormal neurologic examination at discharge, gastrostomy tube feeding, or feeding difficulties. Preliminary data from a prospective trial investigating mild NE (PRIME study, NCT01747863) found that 39% had either abnormal electroencephalography at < 9h of age, an abnormal brain MRI finding, or abnormal neurological exam at discharge. Murray et al. recently reported on 5-year outcomes of infants with mild encephalopathy and showed that 25% had neurodevelopmental disability. These data suggest that mild NE likely carries a higher risk of impaired neurological outcome then reported previously. Thus it would appear that neuroprotective strategies would be beneficial in this group of infants. Preliminary data suggest that erythropoiesis stimulating agents (ESA) provide neuroprotection, and improve short and long-term neurologic outcome in neonatal brain injury. ESA may work through several 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 established safety and pharmacokinetics in newborns. Because Darbe has an extended circulating half-life with comparable biological activity to EPO, it has the advantage of requiring less frequent administration

Conditions

Neonatal Encephalopathy; Hypoxic-Ischemic Encephalopathy Mild

Study Design

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

Study Groups

Darbepoetin Alpha

IV,10 mcg/kg/dose, Darbepoetin Alpha, one dose at \<24 hours of age

Group Type: EXPERIMENTAL

Darbepoetin Alfa

Intervention Type: DRUG

Single dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age

Placebo

IV, Normal saline (placebo dose), one dose at \<24 hours of age

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

Single dose of normal saline, IV, given at less than 24 hours of age

Interventions

Darbepoetin Alfa

Single dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age

Intervention Type: DRUG

Normal Saline

Single dose of normal saline, IV, given at less than 24 hours of age

Intervention Type: DRUG

Other Intervention Names

Darbe; Darbepoetin

Eligibility Criteria

Inclusion Criteria

1. History of an acute perinatal event (abruption, cord prolapsed, severe fetal heart rate abnormality, or meconium staining)

2. Infant is evaluated for hypothermia therapy and DOES NOT meet clinical criteria for TH.

3. Infant has an IV for clinical treatment

Exclusion Criteria

1. Moderate/Severe encephalopathy on modified Sarnat examination at < 6 hours of age

2. Major congenital and/or chromosomal abnormalities

3. Prenatal diagnosis of brain abnormality or hydrocephalus

4. Severe growth restriction (< 3%)

5. Central venous hematocrit >65%, platelet count >600,000/dL, and/or neutropenia (ANC<500 μL)

6. ECMO

7. Infant judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: collaborator

University of New Mexico

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tara L DuPont, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

MEND 16-330

Identifier Type: -

Identifier Source: org_study_id