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Mild Encephalopathy in the Newborn Treated With Darbepoetin (MEND)

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ClinicalTrials.gov Identifier: NCT03071861
Recruitment Status : Recruiting
First Posted : March 7, 2017
Last Update Posted : January 9, 2018
Sponsor:
Collaborator:
University of Utah
Information provided by (Responsible Party):
University of New Mexico

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 and Gross Motor Function Assessment) will be performed at 12-18 months of age.

Condition or disease Intervention/treatment Phase
Neonatal Encephalopathy Hypoxic-Ischemic Encephalopathy Mild Drug: Darbepoetin Alfa Drug: Normal Saline Phase 2

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mild Encephalopathy in the Newborn Treated With Darbepoetin (MEND)
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Darbepoetin Alpha
IV,10 mcg/kg/dose, Darbepoetin Alpha, one dose at <24 hours of age
Drug: Darbepoetin Alfa
Single dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age
Other Names:
  • Darbe
  • Darbepoetin

Placebo Comparator: Placebo
IV, Normal saline (placebo dose), one dose at <24 hours of age
Drug: Normal Saline
Single dose of normal saline, IV, given at less than 24 hours of age




Primary Outcome Measures :
  1. Neurodevelopmental outcome [ Time Frame: 12-18 months of age ]
    Bayley III and Gross Motor Function Assessment


Secondary Outcome Measures :
  1. Percent of infants with adverse events [ Time Frame: 30 days or until hospital discharge whichever comes first ]
    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.

  2. Percent of infants with seizures [ Time Frame: 30 days or until hospital discharge whichever comes first ]
    development of clinical or electrographic seizures

  3. Percentage of infants who need gavage feeds or gastrostomy at discharge home [ Time Frame: 30 days or until hospital discharge whichever comes first ]
    Infants who require tube feedings at discharge

  4. Ages and Stages questionaire [ Time Frame: 4-12 months of age ]
    developmental screening test

  5. Height measurment [ Time Frame: 18-22 months of age ]
    measured in cm

  6. weight measurement [ Time Frame: 18-22 months of age ]
    measured in kg

  7. Head Circumference measurement [ Time Frame: 18-22 months of age ]
    measured in cm


Other Outcome Measures:
  1. Percent with seizures [ Time Frame: 4-12 months of age ]
    development of clinical or electrographic seizures

  2. Percent with Failure to Thrive [ Time Frame: 4-12 months of age ]
    Growth at <3%

  3. percent using early intervention services [ Time Frame: 4-22 months of age ]
    child is enrolled in an early intervention program

  4. Percent with hearing impairment [ Time Frame: 18-22 months of age ]
    Child requires a hearing device

  5. Percent with vision impairment [ Time Frame: 18-22 months of age ]
    requires corrective lenses



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Ages Eligible for Study:   up to 24 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Infants will be eligible for the MEND trial if they have a gestational age > 34 weeks by best obstetric estimate, are <24 hours old and have evidence of mild encephalopathy as defined by Shankaran et al based on a modified Sarnat examination performed at <6 hours of age.

  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 (< 1800g)
  5. Central venous hematocrit >65%, platelet count >600,000/dL, and/or neutropenia (ANC<500 μL)
  6. Maternal history of major vascular thrombosis or multiple fetal losses (> 3 spontaneous abortions)
  7. ECMO
  8. Infant judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist

Information from the National Library of Medicine

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): NCT03071861


Contacts
Contact: Tara L DuPont, MD 5052720180 tldupont@salud.unm.edu
Contact: Robin Ohls, MD 5052720180 rohls@salud.unm.edu

Locations
United States, New Mexico
UNM Children's Hospital Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Tara L DuPont, MD    505-272-0180    tldupont@salud.unm.edu   
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Mariana Baserga, MD    801-587-7510    mariana.baserga@hsc.utah.edu   
Sponsors and Collaborators
University of New Mexico
University of Utah
Investigators
Study Chair: John Philips, MD University of New Mexico

Responsible Party: University of New Mexico
ClinicalTrials.gov Identifier: NCT03071861     History of Changes
Other Study ID Numbers: MEND 16-330
First Posted: March 7, 2017    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of New Mexico:
darbepoetin
Brain Diseases

Additional relevant MeSH terms:
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Central Nervous System Diseases
Nervous System Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain
Darbepoetin alfa
Hematinics