Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Phase 2

Recruiting

• Conditions: Perinatal Stroke; PAIS; Neonatal Stroke
• Interventions: Drug: Darbepoetin Alfa; Drug: Saline

• Registration Number: NCT03171818
• Lead Sponsor: UMC Utrecht

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-24
• Study First Submitted QC: 2017-05-30
• Study First Posted: 2017-05-31
• Study Start: 2017-07-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-06
• Last Update Posted: 2023-12-07
• Primary Completion: 2024-12-31
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Darbepoetin	Darbepoetin Alfa	Darbepoetin alfa (Aranesp, Amgen)
Placebo	Saline	Saline

Primary Outcome Measures

Name	Time	Method
Change in stroke tissue loss	6-8 weeks of age	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.

Secondary Outcome Measures

Name	Time	Method
Neurodevelopment	18 months of age	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).
Neurological assessment	18 months of age	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.
Reorganization of corticospinal connectivity	6-8 weeks of age	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.
Development of Cerebral Palsy	18 months of age	Development of Unilateral Spastic Cerebral Palsy (USCP) using the Gross Motor Function Classification system (GMFCS) and compare this between groups (darbepoetin vs placebo).

Trial Locations

Locations (1)

Wilhelmina Childrens Hostpital/University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands