Deferoxamine in Aneurysmal Subarachnoid Hemorrhage Trial

NCT ID: NCT02875262

Last Updated: 2023-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-02

Study Completion Date

2024-06-01

Brief Summary

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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

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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

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Intracranial Aneurysm Subarachnoid Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Treatment

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

Group Type EXPERIMENTAL

Deferoxamine

Intervention Type DRUG

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

placebo

NaCl 0.9% in similar dosis to treatment arm

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type OTHER

placebo (NaCl 0.9%) in equal dose to treatment

Interventions

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Deferoxamine

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

Intervention Type DRUG

placebo

placebo (NaCl 0.9%) in equal dose to treatment

Intervention Type OTHER

Other Intervention Names

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desferal

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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).

* Tachypnea (respiratory rate \>30)
* SpO2 \<95%
* Obesity (BMI \>30)
* Acidosis (pH \<7.35)
* Hypoalbuminemia (albumin \<3.5 g/dL)
* concurrent use of chemotherapy
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Center Groningen

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeroen Boogaarts, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Radboudumc

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status NOT_YET_RECRUITING

Countries

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Netherlands

Central Contacts

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Jeroen Boogaarts, M.D., Ph.D.

Role: CONTACT

00310243615085

Ronald Bartels, M.D., Ph.D.

Role: CONTACT

00310243615085

Facility Contacts

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Jeroen Boogaarts, M.D., Ph.D.

Role: primary

0031243615085

Joost de Vries, M.D., Ph.D.

Role: backup

0031243615085

Marc van Dijk, M.D., Ph.,D.

Role: primary

00310503616161

Rob Groen, M.D., Ph.,D.

Role: backup

00310503616161

References

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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.

Reference Type DERIVED
PMID: 33236783 (View on PubMed)

Other Identifiers

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NL58448.091.16

Identifier Type: -

Identifier Source: org_study_id

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