Intracranial AneurysmPhase 1/2DASHNCT02875262
Deferoxamine in Aneurysmal Subarachnoid Hemorrhage Trial
A Phase 1/2 study testing Deferoxamine in people with Intracranial Aneurysm and Subarachnoid Hemorrhage, run by Radboud University Medical Center at 2 sites in Netherlands.
Trial summary
Aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke in which secondary neurological deterioration is an important cause of mortality and morbidity. These secondary changes, so called delayed cerebral ischemia (DCI), are caused by lysis of erythrocytes which can react to form iron, an toxic substance to the… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Intracranial Aneurysm, Subarachnoid Hemorrhage
- What is being tested?
- Deferoxamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesNetherlands
- Study dates
- 2 Dec 2022to 1 Jun 2024
- Phase
- Phase 1/2
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- subarachnoid hemorrhage diagnosed by CT on admission,
- Randomizable within 72 hours of subarachnoid hemorrhage,
- Saccular intracranial aneurysm proven by cerebral angiography or CTA,
- Surgical or endovascular obliteration is performed,
- Able to obtain written informed consent from patient or surrogate.
- Patients in a good clinical grade (WFNS 1-3)
Who cannot join
- Pregnancy, as confirmed by routine urine test on admission,
- Abnormal renal function at time of randomization (GFR <60 mL/min)
- Elevated liver function test at time of randomization (AST > 45 U/L and ALT > 35 U/L.)
- History of liver disease or active liver disease, Active renal disease,
- Hypersensitivity to deferoxamine,
- Patient taking medication not recommended for concomitant use with deferoxamine as per the product label (e.g. high dose vit. C medication).
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- Patients not able to complete the study follow-up the presence of 4 or more of the following exclusion criteria (risk modifiers for ARDS):
- Tachypnea (respiratory rate >30)
- SpO2 <95%
- Obesity (BMI >30)
- Acidosis (pH <7.35)
- Hypoalbuminemia (albumin <3.5 g/dL)
- concurrent use of chemotherapy
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites, 2 recruiting
- Not yet recruiting
University Medical Center Groningen
Groningen, 9713 GZ
Marc van Dijk, M.D., Ph.,D., 00310503616161, j.m.c.van.dijk@umcg.nl
Rob Groen, M.D., Ph.,D., 00310503616161, r.j.m.groen@umcg.nl
- Recruiting
Radboudumc
Nijmegen, Gelderland, 6500 HB
Jeroen Boogaarts, M.D., Ph.D., 0031243615085, jeroen.boogaarts@radboudumc.nl
Joost de Vries, M.D., Ph.D., 0031243615085, joost.devries@radboudumc.nl
About this study
Aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke in which secondary neurological deterioration is an important cause of mortality and morbidity. These secondary changes, so called delayed cerebral ischemia (DCI), are caused by lysis of erythrocytes which can react to form iron, an toxic substance to the brain. Iron chelators remove the excess of iron and are standard care in iron-overloaded patients. Deferoxamine (DFO) an chelator has not been evaluated in SAH patients. This study evaluates the safety of deferoxamine in SAH patients.
Read the detailed description
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke affecting relatively young patients. It has an incidence of about 7 per 100,000. Associated economic costs are high. Treatment of the aneurysm to prevent rebleeding is the primary goal. Nevertheless, 3 to 12 days after the initial bleeding secondary ischemic changes occur in 30% of the patients. This delayed cerebral ischemia (DCI) remains the most important cause of mortality and morbidity in patients surviving aneurysm treatment.
Aneurysmal SAH exposes the brain to erythrocytes. Several days after the hemorrhage lysis of erythrocytes takes place and the brain is exposed to high concentrations of hemoglobin. Elevated hemoglobin concentrations are present not only at the basal surface of the brain, but also distributed around the brain and into deeper layers of the cortex. Heme is degraded by heme-oxygenase into carbon monoxide, biliverdin and iron. Free iron can react with H2O and O2- to form hydroxyl radicals (OH*). The generation of hydroxyl radicals in this cascade, known as the Haber-Weiss or Fenton reaction, leads to extraction of hydrogen from unsaturated lipids in the cell membrane and initiates lipid peroxidation. Additionally it can exacerbate excitotoxicity by increased intracellular iron accumulation.
Iron chelators remove the excess of iron and are standard care in iron-overloaded patients. The use of iron chelators for SAH has been subject of animal studies with promising results on reduced vasospasm, oxidative stress, neuronal cell death and mortality. No clinical study for the use of deferoxamine in aneurysmal subarachnoid hemorrhage has been performed. A safety study for the use of Deferoxamine in patients in intracerebral hemorrhage (which is distinct from subarachnoid hemorrhage) has been performed. There were no associated serious adverse events or mortality, Deferoxamine is a chelator is used for more than 40 years in patients with iron overload diseases. This study investigates the safety and tolerability of deferoxamine versus placebo in patients with SAH for 3 consecutive days.
- Conditions
- Intracranial Aneurysm, Subarachnoid Hemorrhage
- Being tested
- Deferoxamine, placebo
- Keywords
- intracranial aneurysm, subarachnoid hemorrhage, stroke, chelator
- Medical subject headings
- Intracranial Aneurysm, Subarachnoid Hemorrhage, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferoxamineDrug
Also called desferal
Patients will be given deferoxamine 32 mg/kg/day (max iv rate 15 mg/kg/hr), patients with ferritin levels between 2,000 and 3,000 ng/ml will receive 32 mg/kg/day and patients with serum ferritin levels below 2,000 ng/ml wil receive 25 mg/kg/day.during 3 days
placeboOther
placebo (NaCl 0.9%) in equal dose to treatment
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients will be given deferoxamine 32 mg/kg/day (max iv rate 15 mg/kg/hr), patients with ferritin levels between 2,000 and 3,000 ng/ml will receive 32 mg/kg/day and patients with serum ferritin levels below 2,000 ng/ml wil receive 25 mg/kg/day. duration 3 days Receives: Drug: Deferoxamine |
| placebo | Placebo comparator | NaCl 0.9% in similar dosis to treatment arm Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety (drug related adverse events; i.e. renal and hepatic dysfunction)
drug related adverse events; i.e. renal and hepatic dysfunction, ARDS
Measured: 6 months
Secondary outcomes (1)
efficacy (new cerebral ischemia compared between intervenation and placebo)
number of patients with delayed cerebral ischemia, which is defined by new, not treatment related cerebral ischemia as registered on CT or MR imaging
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2016 (estimated)
- Study start2 Dec 2022
- Primary completion1 Jan 2024 (estimated)
- Study completion1 Jun 2024 (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 Intracranial AneurysmStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen
- Responsible party
- Sponsor
- Investigators
- Jeroen Boogaarts, M.D., Ph.D., Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02875262
- Sponsor's protocol ID
- NL58448.091.16
- Acronym
- DASH
- Status last verified
- Apr 2023
- First submitted
- 20 Jul 2016
- Last updated
- 24 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: core data will be published
Publications
Van der Loo LE, Aquarius R, Teernstra O, Klijn K, Menovsky T, van Dijk JMC, Bartels R, Boogaarts HD. Iron chelators for acute stroke. Cochrane Database Syst Rev. 2020 Nov 24;11(11):CD009280. doi: 10.1002/14651858.CD009280.pub3.
PubMed 33236783
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deferoxamine in Aneurysmal Subarachnoid Hemorrhage Trial
- ClinicalTrials.gov ID
- NCT02875262
- Acronym / sponsor ID
- DASH / NL58448.091.16
- Conditions
- Intracranial Aneurysm, Subarachnoid Hemorrhage
- Keywords
- intracranial aneurysm, subarachnoid hemorrhage, stroke, chelator
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- University Medical Center Groningen
- Study start
- 2 Dec 2022 (actual)
- Primary completion
- 1 Jan 2024 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 23 Aug 2016 (estimated)
- 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.
Aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke in which secondary neurological deterioration is an important cause of mortality and morbidity. These secondary changes, so called delayed cerebral ischemia (DCI), are caused by lysis of erythrocytes which can react to form iron, an toxic substance to the brain. Iron chelators remove the excess of iron and are standard care in iron-overloaded patients. Deferoxamine (DFO) an chelator has not been evaluated in SAH patients. This study evaluates the safety of deferoxamine in SAH patients.
Detailed description
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke affecting relatively young patients. It has an incidence of about 7 per 100,000. Associated economic costs are high. Treatment of the aneurysm to prevent rebleeding is the primary goal. Nevertheless, 3 to 12 days after the initial bleeding secondary ischemic changes occur in 30% of the patients. This delayed cerebral ischemia (DCI) remains the most important cause of mortality and morbidity in patients surviving aneurysm treatment.
Aneurysmal SAH exposes the brain to erythrocytes. Several days after the hemorrhage lysis of erythrocytes takes place and the brain is exposed to high concentrations of hemoglobin. Elevated hemoglobin concentrations are present not only at the basal surface of the brain, but also distributed around the brain and into deeper layers of the cortex. Heme is degraded by heme-oxygenase into carbon monoxide, biliverdin and iron. Free iron can react with H2O and O2- to form hydroxyl radicals (OH*). The generation of hydroxyl radicals in this cascade, known as the Haber-Weiss or Fenton reaction, leads to extraction of hydrogen from unsaturated lipids in the cell membrane and initiates lipid peroxidation. Additionally it can exacerbate excitotoxicity by increased intracellular iron accumulation.
Iron chelators remove the excess of iron and are standard care in iron-overloaded patients. The use of iron chelators for SAH has been subject of animal studies with promising results on reduced vasospasm, oxidative stress, neuronal cell death and mortality. No clinical study for the use of deferoxamine in aneurysmal subarachnoid hemorrhage has been performed. A safety study for the use of Deferoxamine in patients in intracerebral hemorrhage (which is distinct from subarachnoid hemorrhage) has been performed. There were no associated serious adverse events or mortality, Deferoxamine is a chelator is used for more than 40 years in patients with iron overload diseases. This study investigates the safety and tolerability of deferoxamine versus placebo in patients with SAH for 3 consecutive days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: DeferoxaminePatients will be given deferoxamine 32 mg/kg/day (max iv rate 15 mg/kg/hr), patients with ferritin levels between 2,000 and 3,000 ng/ml will receive 32 mg/kg/day and patients with serum ferritin levels below 2,000 ng/ml wil receive 25 mg/kg/day. duration 3 days |
| placebo | Placebo comparator | Other: placeboNaCl 0.9% in similar dosis to treatment arm |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- subarachnoid hemorrhage diagnosed by CT on admission,
- Randomizable within 72 hours of subarachnoid hemorrhage,
- Saccular intracranial aneurysm proven by cerebral angiography or CTA,
- Surgical or endovascular obliteration is performed,
- Able to obtain written informed consent from patient or surrogate.
Key exclusion criteria (13 listed)
- Pregnancy, as confirmed by routine urine test on admission,
- Abnormal renal function at time of randomization (GFR <60 mL/min)
- Elevated liver function test at time of randomization (AST > 45 U/L and ALT > 35 U/L.)
- History of liver disease or active liver disease, Active renal disease,
- Hypersensitivity to deferoxamine,
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 |
|---|---|---|
| DeferoxamineAlso: desferalPatients will be given deferoxamine 32 mg/kg/day (max iv rate 15 mg/kg/hr), patients with ferritin levels between 2,000 and 3,000 ng/ml will receive 32 mg/kg/day and patients with serum ferritin levels below 2,000 ng/ml wil receive 25 mg/kg/day.during 3 days | Drug | Treatment |
| placeboplacebo (NaCl 0.9%) in equal dose to treatment | Other | placebo |
Primary outcome
safety (drug related adverse events; i.e. renal and hepatic dysfunction)
Time frame: 6 months
drug related adverse events; i.e. renal and hepatic dysfunction, ARDS
1 secondary outcome
efficacy (new cerebral ischemia compared between intervenation and placebo)
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2023.
- Derived from this study: PubMed 33236783Van der Loo LE, Aquarius R, Teernstra O, Klijn K, Menovsky T, van Dijk JMC, Bartels R, Boogaarts HD. Iron chelators for acute stroke. Cochrane Database Syst Rev. 2020 Nov 24;11(11):CD009280. doi: 10.1002/14651858.CD009280.pub3.
- Individual participant dataSharing planned: Yes. core data will be published
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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.
Jeroen Boogaarts, M.D., Ph.D. principal investigator
Radboud University Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Deferoxamine in people with Intracranial Aneurysm and Subarachnoid Hemorrhage, run by Radboud University Medical Center at 2 sites 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 6 inclusion and 13 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 24 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Jeroen Boogaarts, M.D., Ph.D. (00310243615085, jeroen.boogaarts@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety (drug related adverse events; i.e. renal and hepatic dysfunction) (time frame: 6 months). 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 NCT02875262, 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 24 Apr 2023.