NCT03071861: MEND

Mild Encephalopathy in the Newborn Treated With Darbepoetin

Completed Phase 2 Results posted Last updated 21 December 2023

What this trial tests

Phase 2 trial testing Darbepoetin Alfa in Neonatal Encephalopathy in 28 participants. Completed in 1 September 2022.

Timeline

1 December 2017

Primary endpoint
1 December 2019

1 September 2022

Quick facts

Lead sponsor	University of New Mexico
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	28
Start date	1 December 2017
Primary completion	1 December 2019
Estimated completion	1 September 2022
Sites	1 location across United States

Drugs / interventions tested

• Darbepoetin Alfa (DARBEPOETIN ALFA) — full drug profile →
• Normal Saline

Conditions studied

• Neonatal Encephalopathy — all drugs for Neonatal Encephalopathy →
• Hypoxic-Ischemic Encephalopathy Mild — all drugs for Hypoxic-Ischemic Encephalopathy Mild →

Sponsor

University of New Mexico

Who can join

Adults 1 Hour to 24 Hours, any sex, with Neonatal Encephalopathy or Hypoxic-Ischemic Encephalopathy Mild. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Normal Neurodevelopment Primary · 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.

Group	Value	95% CI
Darbepoetin Alpha	13
Placebo	14

Percent of Infants With Adverse Events Secondary · 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.

Group	Value	95% CI
Darbepoetin Alpha	0
Placebo	0

Percent of Infants With Seizures Secondary · 30 days or until hospital discharge whichever comes first

development of clinical or electrographic seizures

Group	Value	95% CI
Darbepoetin Alpha	0
Placebo	0

Percentage of Infants Who Need Gavage Feeds or Gastrostomy at Discharge Home Secondary · 30 days or until hospital discharge whichever comes first

Infants who require tube feedings at discharge

Group	Value	95% CI
Darbepoetin Alpha	0
Placebo	0

Percent With Failure to Thrive Secondary · 9 months of age

Growth at \<3%

Group	Value	95% CI
Darbepoetin Alpha	0
Placebo	0

Percent With Hearing Impairment Secondary · 9 months of age

Child requires a hearing device

Group	Value	95% CI
Darbepoetin Alpha	0
Placebo	0

Percent With Vision Impairment Secondary · 9 months of age

requires corrective lenses

Group	Value	95% CI
Darbepoetin Alpha	0
Placebo	0

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current and Emerging Therapies in the Management of Hypoxic Ischemic Encephalopathy in Neonates.
   Nair J, Kumar VHS. · · 2018 · cited 90× · PMID 30029531 · DOI 10.3390/children5070099
2. Neuroprotective therapies in the NICU in term infants: present and future.
   Molloy EJ, El-Dib M, Juul SE, Benders M, et al · · 2023 · cited 61× · PMID 36195634 · DOI 10.1038/s41390-022-02295-2
3. Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy.
   Ranjan AK, Gulati A. · · 2023 · cited 41× · PMID 37892791 · DOI 10.3390/jcm12206653
4. Ferroptosis: A Promising Therapeutic Target for Neonatal Hypoxic-Ischemic Brain Injury.
   Peeples ES, Genaro-Mattos TC. · · 2022 · cited 41× · PMID 35806425 · DOI 10.3390/ijms23137420
5. Mild hypoxic-ischemic encephalopathy (HIE): timing and pattern of MRI brain injury.
   Li Y, Wisnowski JL, Chalak L, Mathur AM, et al · · 2022 · cited 32× · PMID 35354930 · DOI 10.1038/s41390-022-02026-7
6. Free Radicals and Neonatal Brain Injury: From Underlying Pathophysiology to Antioxidant Treatment Perspectives.
   Martini S, Castellini L, Parladori R, Paoletti V, et al · · 2021 · cited 21× · PMID 34943115 · DOI 10.3390/antiox10122012
7. Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines.
   Okazaki K, Nakamura S, Koyano K, Konishi Y, et al · · 2023 · cited 16× · PMID 36776908 · DOI 10.3389/fped.2023.1070743
8. Darbepoetin as a neuroprotective agent in mild neonatal encephalopathy: a randomized, placebo-controlled, feasibility trial.
   DuPont TL, Baserga M, Lowe J, Zamora T, et al · · 2021 · cited 10× · PMID 33986477 · DOI 10.1038/s41372-021-01081-y