PAISPhase 2DINOSAURNCT03171818
Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration
A Phase 2 study testing Darbepoetin Alfa and Saline in people with PAIS and Neonatal Stroke, run by UMC Utrecht at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 7 days
- Conditions the study is for
- PAIS, Neonatal Stroke, Perinatal Stroke
- What is being tested?
- Darbepoetin Alfa and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jul 2017to 1 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Wilhelmina Childrens Hostpital/University Medical Center Utrecht
Utrecht, 3584 EA
Manon Benders, MD, PhD, +31(0)887554545
Lisanne M Baak, MD, +31(0)887554545, L.M.Baak-3@umcutrecht.nl
About this study
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
- Being tested
- Darbepoetin Alfa, Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darbepoetin AlfaDrug
Also called Aranesp
Darbepoetin alfa (Aranesp, Amgen) 2 doses of 10 microgram/kg i.v.
SalineDrug
Also called Sodium Chloride
The placebo will consist of saline, containing 9.0 g of salt per liter (0.90%) i.v.
| Study group | Role | What they receive |
|---|---|---|
| Darbepoetin | Experimental | Darbepoetin alfa (Aranesp, Amgen) Receives: Drug: Darbepoetin Alfa |
| Placebo | Placebo comparator | Saline Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6-8 weeks of age
Secondary outcomes (4)
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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 18 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2017
- Study start1 Jul 2017
- Primary completion31 Dec 2024 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PAISStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An international multicenter, randomized placebo controlled intervention study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Children's Hospital, The Hospital for Sick Children
- Responsible party
- Principal investigator, dr. M.J.N.L. Benders, UMC Utrecht
- Investigators
- Manon Benders, MD PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03171818
- Sponsor's protocol ID
- NL53975.041.16
- Acronym
- DINOSAUR
- Status last verified
- Dec 2023
- First submitted
- 24 May 2017
- Last updated
- 7 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24321539
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Darbepoetin for Ischemic Neonatal Stroke to Augment Regeneration
- ClinicalTrials.gov ID
- NCT03171818
- Acronym / sponsor ID
- DINOSAUR / NL53975.041.16
- Conditions
- PAIS, Neonatal Stroke, Perinatal Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Alberta Children's Hospital, The Hospital for Sick Children
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 31 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- An international multicenter, randomized placebo controlled intervention study
| Arm | Type | Receives |
|---|---|---|
| Darbepoetin | Experimental | Drug: Darbepoetin AlfaDarbepoetin alfa (Aranesp, Amgen) |
| Placebo | Placebo comparator | Drug: SalineSaline |
Who may qualify
- Ages
- Up to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Darbepoetin AlfaAlso: AranespDarbepoetin alfa (Aranesp, Amgen) 2 doses of 10 microgram/kg i.v. | Drug | Darbepoetin |
| SalineAlso: Sodium ChlorideThe placebo will consist of saline, containing 9.0 g of salt per liter (0.90%) i.v. | Drug | Placebo |
Primary outcome
Change in stroke tissue loss
Time frame: 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.
4 secondary outcomes
Reorganization of corticospinal connectivity
Time frame: 6-8 weeks of age
Neurodevelopment
Time frame: 18 months of age
Neurological assessment
Time frame: 18 months of age
Development of Cerebral Palsy
Time frame: 18 months of age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2023.
- Background: PubMed 24321539Benders 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manon Benders, MD PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Darbepoetin Alfa and Saline in people with PAIS and Neonatal Stroke, run by UMC Utrecht at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Manon Benders, MD PhD (+31 88 755 5555, m.benders@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in stroke tissue loss (time frame: 6-8 weeks of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03171818, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2023.