Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Study Overview
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Brief Summary
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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.

Official Title
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Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Conditions
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PAIS, Neonatal Stroke, Perinatal Stroke

Intervention / Treatment
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* Drug: Darbepoetin Alfa
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An international multicenter, randomized placebo controlled intervention study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darbepoetin<br>Darbepoetin alfa (Aranesp, Amgen) | Drug: Darbepoetin Alfa<br>* Darbepoetin alfa (Aranesp, Amgen) 2 doses of 10 microgram/kg i.v.<br>* Other names: Aranesp;|
| Placebo Comparator: Placebo<br>Saline | Drug: Saline<br>* The placebo will consist of saline, containing 9.0 g of salt per liter (0.90%) i.v.<br>* Other names: Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 |