Neonatal EncephalopathyPhase 2MENDNCT03071861
Mild Encephalopathy in the Newborn Treated With Darbepoetin
A Phase 2 study testing Darbepoetin Alfa and Normal Saline in people with Neonatal Encephalopathy and Hypoxic-Ischemic Encephalopathy Mild, run by University of New Mexico at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 hour to 24 hours
- Conditions the study is for
- Neonatal Encephalopathy, Hypoxic-Ischemic Encephalopathy Mild
- What is being tested?
- Darbepoetin Alfa and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2017to 1 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
None listed.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Darbepoetin Alfa, Normal Saline
- Keywords
- darbepoetin, Brain Diseases
- Medical subject headings
- Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darbepoetin AlfaDrug
Also called Darbe, Darbepoetin
Single dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age
Normal SalineDrug
Single dose of normal saline, IV, given at less than 24 hours of age
| Study group | Role | What they receive |
|---|---|---|
| Darbepoetin Alpha | Experimental | IV,10 mcg/kg/dose, Darbepoetin Alpha, one dose at <24 hours of age Receives: Drug: Darbepoetin Alfa |
| Placebo | Placebo comparator | IV, Normal saline (placebo dose), one dose at <24 hours of age Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normal Neurodevelopment
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.
Measured: 9 - 12 months of age
Secondary outcomes (3)
Percent of Infants 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.
Measured: 30 days or until hospital discharge whichever comes first
Percent of Infants With Seizures
development of clinical or electrographic seizures
Measured: 30 days or until hospital discharge whichever comes first
Percentage of Infants Who Need Gavage Feeds or Gastrostomy at Discharge Home
Infants who require tube feedings at discharge
Measured: 30 days or until hospital discharge whichever comes first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2017
- Study start1 Dec 2017
- Primary completion1 Dec 2019
- Study completion1 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neonatal EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of New Mexico
- Sponsor type
- University, hospital or other
- Collaborators
- University of Utah
- Responsible party
- Sponsor
- Investigators
- Tara L DuPont, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03071861
- Sponsor's protocol ID
- MEND 16-330
- Acronym
- MEND
- Status last verified
- Dec 2023
- First submitted
- 1 Dec 2016
- Last updated
- 21 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mild Encephalopathy in the Newborn Treated With Darbepoetin (MEND)
- ClinicalTrials.gov ID
- NCT03071861
- Acronym / sponsor ID
- MEND / MEND 16-330
- Keywords
- darbepoetin, Brain Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of New MexicoUniversity, hospital or other
- Collaborators
- University of Utah
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 7 Mar 2017 (actual)
- Results
- Posted 25 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Darbepoetin Alpha | Experimental | Drug: Darbepoetin AlfaIV,10 mcg/kg/dose, Darbepoetin Alpha, one dose at <24 hours of age |
| Placebo | Placebo comparator | Drug: Normal SalineIV, Normal saline (placebo dose), one dose at <24 hours of age |
Who may qualify
- Ages
- 1 hour to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (0 listed)
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Darbepoetin AlfaAlso: Darbe, DarbepoetinSingle dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age | Drug | Darbepoetin Alpha |
| Normal SalineSingle dose of normal saline, IV, given at less than 24 hours of age | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Percent of Infants With Adverse Events
Time frame: 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
Percentage of Infants Who Need Gavage Feeds or Gastrostomy at Discharge Home
Time frame: 30 days or until hospital discharge whichever comes first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Neonatal Encephalopathy
Not yet recruitingObservational study
This Multicentre Study Compares aCUP-E With Standard Electrodes During aEEG Monitoring in NICU Newborns at Risk of Encephalopathy, Assessing Recording Quality, Reliability, Ease of Use and Safety.
Encephalopathy
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
RecruitingPhase 2/3
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
Hypoxic-Ischemic Encephalopathy
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
RecruitingObservational study
The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
Oxidative Phosphorylation Deficiencies, Electron Transport Chain Disorders, Mitochondrial
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tara L DuPont, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Darbepoetin Alfa and Normal Saline in people with Neonatal Encephalopathy and Hypoxic-Ischemic Encephalopathy Mild, run by University of New Mexico at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normal Neurodevelopment (time frame: 9 - 12 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.