Neonatal Stroke, PAIS, Perinatal Stroke
Conditions
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.
Interventions
DRUGDarbepoetin Alfa
Darbepoetin alfa (Aranesp, Amgen) 2 doses of 10 microgram/kg i.v.
DRUGSaline
The placebo will consist of saline, containing 9.0 g of salt per liter (0.90%) i.v.
Sponsors
Alberta Children's Hospital
The Hospital for Sick Children
UMC Utrecht
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This will be a double-blinded study, meaning that both the patient (and his/her parents) and the health care providers, including neonatologist, pediatrician, nurses, physiotherapists, etc, are not allowed to know what treatment the patient has been given. Those that collect outcome parameters, such as MRI data and neurodevelopmental outcome, are also unaware of treatment allocation, meaning that blinding will be maintained during the full study-period of 18 months.
Intervention model description
An international multicenter, randomized placebo controlled intervention study
Eligibility
Sex/Gender
ALL
Age
No minimum to 7 Days
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
Countries
Netherlands
Contacts
Primary ContactManon Benders, MD PhD
Backup ContactLisanne M Baak, MD
Outcome results
None listed