Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Perinatal Stroke Clinical Trial

— DINOSAUR  

Official title:

Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03171818
• Other study ID #: NL53975.041.16
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2017
• Est. completion date: June 1, 2025

Study information

• Verified date: December 2023
• Source: UMC Utrecht
• Contact: Manon Benders, MD PhD
• Phone: +31 88 755 5555
• Email: m.benders[@]umcutrecht.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to perform a randomized double-blind placebo controlled prospective study in newborn infants with MRI confirmed Middle Cerebral Artery (MCA) Perinatal Arterial Ischemic Stroke (PAIS) with darbepoetin. It will be investigated whether intravenous administered darbepoetin can induce the formation of neuronal tissue and restore brain function in neonates who suffered from PAIS compared to placebo treated controls. The ultimate goal of this study is therefore to develop a therapy using erythropoiesis-stimulating agents (ESA) such as darbepoetin to reduce or even prevent lifelong consequences of PAIS-related brain injury in this group of term newborns.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 1, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Days

Eligibility

Inclusion Criteria:

• Newborns = 36+0 weeks of gestation, both male and female
• MRI confirmed diagnosis of acute PAIS, in the MCA region with involvement of the cortical spinal tract (e.g. Posterior Limb of Internal Capsule [PLIC] or peduncles) within one week after birth
• Written informed consent from custodial parent(s)

Exclusion Criteria:

• Moderate -severe Hypoxic-Ischemic Encephalopathy (HIE) with or without hypothermia therapy
• Any proven or suspected major congenital anomaly, chromosomal disorder, metabolic disorder;
• Presence of a serious infection of the central nervous system;
• No realistic prospect of survival, (e.g. severe brain injury), at the discretion of the attending physician.
• Infant for whom withdrawal of supportive care is being considered.

Related Conditions & MeSH terms

• Neonatal Stroke
• PAIS
• Perinatal Stroke
• Stroke

Intervention

Drug:
• Darbepoetin Alfa
Darbepoetin alfa (Aranesp, Amgen) 2 doses of 10 microgram/kg i.v.
• Saline
The placebo will consist of saline, containing 9.0 g of salt per liter (0.90%) i.v.

Locations

Country	Name	City	State
Netherlands	Wilhelmina Childrens Hostpital/University Medical Center Utrecht	Utrecht

Sponsors (3)

Lead Sponsor	Collaborator
UMC Utrecht	Alberta Children's Hospital, The Hospital for Sick Children

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Benders MJ, van der Aa NE, Roks M, van Straaten HL, Isgum I, Viergever MA, Groenendaal F, de Vries LS, van Bel F. Feasibility and safety of erythropoietin for neuroprotection after perinatal arterial ischemic stroke. J Pediatr. 2014 Mar;164(3):481-6.e1-2. doi: 10.1016/j.jpeds.2013.10.084. Epub 2013 Dec 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in stroke tissue loss	The primary objective is to determine whether there is a difference in the degree in stroke tissue loss between darbepoetin and placebo treatment, which will be measured by the change in lesion size between the time of onset of the insult and 6-8 weeks of age. The primary endpoint will be estimated using advanced volumetric magnetic resonance (MRI) techniques, performed within one week after clinical presentation and at 6-8 weeks of age.	6-8 weeks of age
Secondary	Reorganization of corticospinal connectivity	To assess whether there are differences between darbepoetin and placebo treatment in Diffusion Tensor Imaging (DTI) parameters of selected regions of interest. DTI-MRI techniques are performed at 6-8 weeks of age.	6-8 weeks of age
Secondary	Neurodevelopment	To assess cognitive and motor development at 18 months of age using the Bayley Scales of Infants and Toddler Development (BSITD)-III scores compare them between groups (darbepoetin vs placebo).	18 months of age
Secondary	Neurological assessment	To assess neurological deficit and function using the Pediatric Stroke Outcome Measure (PSOM) and compare this score between groups (darbepoetin vs placebo). The PSOM is performed at 18 months of age.	18 months of age
Secondary	Development of Cerebral Palsy	Development of Unilateral Spastic Cerebral Palsy (USCP) using the Gross Motor Function Classification system (GMFCS) and compare this between groups (darbepoetin vs placebo).	18 months of age