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Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration (DINOSAUR)

Primary Purpose

PAIS, Neonatal Stroke, Perinatal Stroke

Status

Recruiting

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

Darbepoetin Alfa

Saline

About this trial

This is an interventional treatment trial for PAIS

Eligibility Criteria

undefined - 7 Days (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Wilhelmina Childrens Hostpital/University Medical Center UtrechtRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Darbepoetin

Placebo

Arm Description

Darbepoetin alfa (Aranesp, Amgen)

Saline

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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).

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.

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).

Full Information

NCT ID

NCT03171818

First Posted

May 24, 2017

Last Updated

October 6, 2021

Sponsor

UMC Utrecht

Collaborators

Alberta Children's Hospital, The Hospital for Sick Children

1. Study Identification

Unique Protocol Identification Number

NCT03171818

Brief Title

Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Acronym

DINOSAUR

Official Title

Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Recruiting

Study Start Date

July 1, 2017 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

UMC Utrecht

Collaborators

Alberta Children's Hospital, The Hospital for Sick Children

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

PAIS, Neonatal Stroke, Perinatal Stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

An international multicenter, randomized placebo controlled intervention study

Masking

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Darbepoetin

Arm Type

Experimental

Arm Description

Darbepoetin alfa (Aranesp, Amgen)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Saline

Intervention Type

Drug

Intervention Name(s)

Darbepoetin Alfa

Other Intervention Name(s)

Aranesp

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Saline

Other Intervention Name(s)

Sodium Chloride

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in stroke tissue loss

Description

Time Frame

6-8 weeks of age

Secondary Outcome Measure Information:

Title

Reorganization of corticospinal connectivity

Description

Time Frame

6-8 weeks of age

Title

Neurodevelopment

Description

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).

Time Frame

18 months of age

Title

Neurological assessment

Description

Time Frame

18 months of age

Title

Development of Cerebral Palsy

Description

Development of Unilateral Spastic Cerebral Palsy (USCP) using the Gross Motor Function Classification system (GMFCS) and compare this between groups (darbepoetin vs placebo).

Time Frame

18 months of age

10. Eligibility

Sex

All

Maximum Age & Unit of Time

7 Days

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Manon Benders, MD PhD

Phone

+31 88 755 5555

m.benders@umcutrecht.nl

First Name & Middle Initial & Last Name or Official Title & Degree

Nienke Wagenaar, MD

Phone

+31 88 755 5555

n.wagenaar@umcutrecht.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Manon Benders, MD PhD

Organizational Affiliation

UMC Utrecht

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wilhelmina Childrens Hostpital/University Medical Center Utrecht

City

Utrecht

ZIP/Postal Code

3584 EA

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Manon Benders, MD, PhD

Phone

+31(0)887554545

First Name & Middle Initial & Last Name & Degree

Nienke Wagenaar, MD

Phone

+31(0)887554545

Ext

63630

n.wagenaar@umcutrecht.nl

First Name & Middle Initial & Last Name & Degree

Linda S de Vries, MD, PhD

First Name & Middle Initial & Last Name & Degree

Manon JN Benders, MD, PhD

First Name & Middle Initial & Last Name & Degree

Nienke Wagenaar, MD

First Name & Middle Initial & Last Name & Degree

Floris Groenendaal, MD, PhD

First Name & Middle Initial & Last Name & Degree

Jeroen Dudink, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24321539

Citation

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.

Results Reference

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Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration

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