Deferoxamine for Subarachnoid Hemorrhage
(DISH Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Aditya S. Pandey, MD
Must not be taking: Antiplatelets, Anticoagulants, Iron supplements
Disqualifiers: Giant aneurysm, Severe anemia, others
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Aneurysmal subarachnoid hemorrhage (aSAH) has a high incidence of mortality and significant morbidity, with mortality exceeding 30% in the first two days.The initial injury is related to increasing intracranial pressure, cerebral edema, and neuronal injuries associated with the release of iron. Iron has been shown to increase the incidence of cerebral edema, ischemia, and formation of hydrocephalus. Deferoxamine mesylate (DFO), a hydrophilic chelator, creates a stable complex with free iron thus preventing the formation of iron related free radicals.
This trial will evaluate the safety and efficacy of clinical deferoxamine for the treatment of aSAH for patients that are admitted to the hospital at the University of Michigan or Peking University Health Science Center. Eligible participants will be enrolled and randomized to 1 of 2 doses of Deferoxamine or placebo (saline). Information regarding the patients will be collected and followed for up to 6 months post discharge.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using anti-platelet or anticoagulant drugs or taking iron supplements with more than 325 mg of ferrous iron.
What data supports the effectiveness of the drug Deferoxamine for treating subarachnoid hemorrhage?
Research shows that Deferoxamine, an iron-chelating drug, has neuroprotective effects in animal models of intracerebral hemorrhage and ischemic stroke, reducing brain damage and improving recovery. These findings suggest potential benefits for similar conditions like subarachnoid hemorrhage.
12345Is deferoxamine safe for humans?
Deferoxamine has been tested in humans for various conditions, and studies show it is generally well-tolerated. In patients with intracerebral hemorrhage, doses up to 62 mg/kg/day were well-tolerated without increasing serious side effects or death. However, there have been reports of eye-related side effects in some patients, so regular eye check-ups are recommended for those on long-term treatment.
15678How is the drug Deferoxamine unique for treating subarachnoid hemorrhage?
Deferoxamine is unique because it acts as an iron chelator, which means it binds to excess iron that can cause damage after a brain bleed, and it can be administered intranasally to directly target the brain, potentially offering a more effective and less invasive treatment option.
13459Eligibility Criteria
This trial is for patients with a recent brain aneurysm bleed who were independent before the event, can start treatment within 24 hours, and have had their aneurysm secured. They must be able to give consent and not have severe kidney issues, hearing loss, low blood counts, or allergies to deferoxamine.Inclusion Criteria
You have been diagnosed with a brain aneurysm using special imaging tests.
You need to have a Glasgow Coma Scale score of 7 or higher after having an External Ventricular Drain placed if it is needed.
Informed consent obtained by patient or legal authorized representative (LAR)
+5 more
Exclusion Criteria
I have a significant disability, with difficulty in daily activities.
I have a serious lung condition or need home oxygen.
I have severe anemia or need blood transfusions often.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants are randomized to receive either Deferoxamine at one of two doses or placebo for the treatment of aSAH
3 days
Daily in-hospital visits
Follow-up
Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and monitoring for delayed cerebral ischemia
6 months
Regular follow-up visits post-discharge
Participant Groups
The study tests if Deferoxamine (DFO), which binds iron in the body to prevent damage from free radicals, is safe and effective for treating bleeding from a brain aneurysm. Participants will receive either DFO at two different doses or a placebo.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Deferoxamine lower doseExperimental Treatment1 Intervention
Deferoxamine 32 Milligram Per Kilogram (mg/kg)
Group II: Deferoxamine higher doseExperimental Treatment1 Intervention
Deferoxamine 48 mg/kg
Group III: PlaceboPlacebo Group1 Intervention
normal saline
Deferoxamine is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Desferal for:
- Acute Iron Poisoning
- Chronic Iron Overload
🇪🇺 Approved in European Union as Desferal for:
- Iron overload
- Aluminum toxicity
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of MichiganAnn Arbor, MI
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Who Is Running the Clinical Trial?
Aditya S. Pandey, MDLead Sponsor
Michigan Medicine PKUHSC Joint Institute for Translational & Clinical ResearchCollaborator
References
High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. [2021]Hemoglobin degradation products, in particular iron, have been implicated in secondary neuronal injury following intracerebral hemorrhage (ICH). The iron chelator Deferoxamine Mesylate (DFO) exerts diverse neuroprotective effects, reduces perihematoma edema (PHE) and neuronal damage, and improves functional recovery after experimental ICH. We hypothesize that treatment with DFO could minimize neuronal injury and improve outcome in ICH patients. As a prelude to test this hypothesis, we conducted a Phase I, open-label study to determine the tolerability, safety, and maximum tolerated dose (MTD) of DFO in patients with ICH. Intravenous infusions of DFO in doses up to 62 mg/kg/day (up to a maximum of 6000 mg/day) were well-tolerated and did not seem to increase serious adverse events (SAEs) or mortality. We have initiated a multi-center, double-blind, randomized, placebo-controlled, Phase II clinical trial (High Dose Deferoxamine [HI-DEF] in Intracerebral Hemorrhage) to determine if it is futile to move DFO forward to Phase III efficacy evaluation.
Efficacy of desferrioxamine mesylate in intracerebral hematoma: a systemic review and meta-analysis. [2022]Previous meta-analysis had concluded that desferrioxamine mesylate (DFO) could effectively treat intracerebral hematoma (ICH) in animal models. We hope to confirm that DFO could treat ICH patients effectively through the systemic review and meta-analysis of clinical researches.
Heme oxygenase-1-mediated neuroprotection in subarachnoid hemorrhage via intracerebroventricular deferoxamine. [2018]Subarachnoid hemorrhage (SAH) is a devastating disease that affects over 30,000 Americans per year. Previous animal studies have explored the therapeutic effects of deferoxamine (DFX) via its iron-chelating properties after SAH, but none have assessed the necessity of microglial/macrophage heme oxygenase-1 (HO-1 or Hmox1) in DFX neuroprotection, nor has the efficacy of an intracerebroventricular (ICV) administration route been fully examined. We explored the therapeutic efficacy of systemic and ICV DFX in a SAH mouse model and its effect on microglial/macrophage HO-1.
Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. [2021]Deferoxamine (DFO) is a high-affinity iron chelator approved by the Food and Drug Administration for treating iron overload. Preclinical research suggests that systemically administered DFO prevents and treats ischemic stroke damage and intracerebral hemorrhage. However, translation into human trials has been limited, probably because of difficulties with DFO administration. A noninvasive method of intranasal administration has emerged recently as a rapid way to bypass the blood-brain barrier and target therapeutic agents to the central nervous system. We report here that intranasal administration targets DFO to the brain and reduces systemic exposure, and that intranasal DFO prevents and treats stroke damage after middle cerebral artery occlusion (MCAO) in rats. A 6-mg dose of DFO resulted in significantly higher DFO concentrations in the brain (0.9-18.5 microM) at 30 min after intranasal administration than after intravenous administration (0.1-0.5 microM, p
Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis. [2021]Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P
Safety profiles of iron chelators in young patients with haemoglobinopathies. [2017]This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr of age with haemoglobinopathies.
Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. [2021]Treatment with the iron chelator, deferoxamine mesylate (DFO), improves neurological recovery in animal models of intracerebral hemorrhage (ICH). We aimed to evaluate the feasibility, safety, and tolerability of varying dose-tiers of DFO in patients with spontaneous ICH, and to determine the maximum tolerated dose to be adopted in future efficacy studies.
Deferoxamine-related ocular toxicity: incidence and outcome in a pediatric population. [2013]Deferoxamine (DFO) is a chelating agent used widely for the treatment of transfusional hemochromatosis. DFO-related ocular toxicity has been previously reported several times, and many institutions have adopted an ophthalmic screening protocol for patients treated with DFO despite little information regarding the rate of ocular toxicity. Our study aimed to determine the incidence of DFO toxicity at a major pediatric hospital that uses regular ophthalmic screening for all DFO-treated patients.
Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis. [2023]Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX.