Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

NCT03171818 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: NL53975.041.16
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

PAIS; Neonatal Stroke; Perinatal Stroke

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Reorganization of corticospinal connectivity

  6-8 weeks of age

• Neurodevelopment

  18 months of age

• Neurological assessment

  18 months of age

• Development of Cerebral Palsy

  18 months of age

Study Arms (2)

Darbepoetin

EXPERIMENTAL

Darbepoetin alfa (Aranesp, Amgen)

Drug: Darbepoetin Alfa

Placebo

PLACEBO COMPARATOR

Saline

Drug: Saline

Interventions

Darbepoetin Alfa DRUG

Darbepoetin alfa (Aranesp, Amgen) 2 doses of 10 microgram/kg i.v.

Also known as: Aranesp

Darbepoetin

Saline DRUG

The placebo will consist of saline, containing 9.0 g of salt per liter (0.90%) i.v.

Also known as: Sodium Chloride

Placebo

Eligibility Criteria

• Age: Up to 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• UMC Utrecht: lead
• Alberta Children's Hospital: collaborator
• The Hospital for Sick Children: collaborator

Study Sites (1)

Wilhelmina Childrens Hostpital/University Medical Center Utrecht

Utrecht, 3584 EA, Netherlands

RECRUITING

Related 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.

  PMID: 24321539 BACKGROUND

MeSH Terms

Interventions

Darbepoetin alfa; Sodium Chloride

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Manon Benders, MD PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manon Benders, MD PhD

CONTACT

+31 88 755 5555; m.benders@umcutrecht.nl

Lisanne M Baak, MD

CONTACT

+31 88 755 5555; l.m.baak-3@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator UMC Utrecht

Model Details: An international multicenter, randomized placebo controlled intervention study

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 31, 2017
• Study Start: July 1, 2017
• Primary Completion: December 31, 2024
• Study Completion: June 1, 2025
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)