- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03071861
Mild Encephalopathy in the Newborn Treated With Darbepoetin (MEND)
December 1, 2023 updated by: University of New Mexico
Mild Encephalopathy in the Newborn Treated With Darbepoetin (MEND)
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.
Study Overview
Status
Completed
Intervention / Treatment
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
Enrollment (Actual)
28
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Utah
-
Salt Lake City, Utah, United States, 84108
- University of Utah
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 1 year (Child)
Accepts Healthy Volunteers
No
Description
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.
- History of an acute perinatal event (abruption, cord prolapsed, severe fetal heart rate abnormality, or meconium staining)
- Infant is evaluated for hypothermia therapy and DOES NOT meet clinical criteria for TH.
- Infant has an IV for clinical treatment
Exclusion Criteria:
- Moderate/Severe encephalopathy on modified Sarnat examination at < 6 hours of age
- Major congenital and/or chromosomal abnormalities
- Prenatal diagnosis of brain abnormality or hydrocephalus
- Severe growth restriction (< 3%)
- Central venous hematocrit >65%, platelet count >600,000/dL, and/or neutropenia (ANC<500 μL)
- ECMO
- Infant judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Darbepoetin Alpha
IV,10 mcg/kg/dose, Darbepoetin Alpha, one dose at <24 hours of age
|
Single dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age
Other Names:
|
Placebo Comparator: Placebo
IV, Normal saline (placebo dose), one dose at <24 hours of age
|
Single dose of normal saline, IV, given at less than 24 hours of age
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Normal Neurodevelopment
Time Frame: 9 - 12 months of age
|
The Bayley III and Neuromuscular Assessment were completed between 9-12 months of age.
Subjects were abnormal if they had a Bayley III score of less than 70 and/or an abnormal neurological examination.
|
9 - 12 months of age
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
30 days or until hospital discharge whichever comes first
|
Percent of Infants With Seizures
Time Frame: 30 days or until hospital discharge whichever comes first
|
development of clinical or electrographic seizures
|
30 days or until hospital discharge whichever comes first
|
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
|
30 days or until hospital discharge whichever comes first
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent With Seizures
Time Frame: 24 months of age
|
development of clinical or electrographic seizures
|
24 months of age
|
Percent With Failure to Thrive
Time Frame: 9 months of age
|
Growth at <3%
|
9 months of age
|
Percent With Hearing Impairment
Time Frame: 9 months of age
|
Child requires a hearing device
|
9 months of age
|
Percent With Vision Impairment
Time Frame: 9 months of age
|
requires corrective lenses
|
9 months of age
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Tara L DuPont, MD, University of Utah
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2017
Primary Completion (Actual)
December 1, 2019
Study Completion (Actual)
September 1, 2022
Study Registration Dates
First Submitted
December 1, 2016
First Submitted That Met QC Criteria
March 1, 2017
First Posted (Actual)
March 7, 2017
Study Record Updates
Last Update Posted (Estimated)
December 21, 2023
Last Update Submitted That Met QC Criteria
December 1, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MEND 16-330
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hypoxic-Ischemic Encephalopathy Mild
-
Stanford UniversityThrasher Research FundNot yet recruitingHypoxic-Ischemic Encephalopathy Mild | Neonatal EncephalopathyUnited States
-
University of Texas Southwestern Medical CenterChildren's Hospital of Philadelphia; Emory University; University of Washington; University of California, San Francisco and other collaboratorsRecruitingMild Hypoxic Ischemic Encephalopathy of NewbornUnited States
-
Johns Hopkins UniversityUniversity of MarylandCompletedEncephalopathy, Hypoxic-IschemicUnited States
-
Sajjad RahmanUnknownSevere Hypoxic Ischemic Encephalopathy | Moderate Hypoxic Ischemic EncephalopathyTurkey, Egypt, Malaysia, Qatar, Saudi Arabia, United Arab Emirates
-
NICHD Neonatal Research NetworkEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsCompletedHypoxia, Brain | Hypoxia-Ischemia, Brain | Hypoxic-Ischemic Encephalopathy | Infant, Newborn | Ischemic-Hypoxic Encephalopathy | Encephalopathy, Hypoxic-IschemicUnited States
-
Fondazione Policlinico Universitario Agostino Gemelli...RecruitingEncephalopathy, Hypoxic IschemicItaly
-
Cliniques universitaires Saint-Luc- Université...Active, not recruitingEncephalopathy, Hypoxic-IschemicBelgium
-
University Hospital, GrenobleUnknownIschemic-Hypoxic EncephalopathyFrance
-
NICHD Neonatal Research NetworkEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsTerminatedHypoxia, Brain | Hypoxia-Ischemia, Brain | Hypoxic-Ischemic Encephalopathy | Infant, Newborn | Ischemic-Hypoxic Encephalopathy | Encephalopathy, Hypoxic-IschemicUnited States
-
Navy General Hospital, BeijingDaping Hospital and the Research Institute of Surgery of the Third Military... and other collaboratorsUnknownHypoxic-Ischemic EncephalopathyChina
Clinical Trials on Darbepoetin Alfa
-
AmgenCompletedAnemia | Non-Myeloid Malignancies
-
The Hospital for Sick ChildrenCompletedKidney Failure, ChronicCanada
-
AmgenCompleted
-
Kyowa Kirin Co., Ltd.Completed
-
AmgenCompletedLymphoma | Breast Neoplasms | Lung Neoplasms | Multiple Myeloma | Chronic Lymphocytic Leukemia
-
AmgenCompleted