Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH) (DISH)

Aditya S. Pandey, MD

Status and phase: Enrolling; Phase 2

Conditions: Aneurysmal Subarachnoid Hemorrhage

Treatments: Drug: Deferoxamine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04566991

HUM00163868

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aneurysmal SAH confirmed with vascular imaging
• Aneurysm treated with endovascular or microsurgical intervention
• Hunt-Hess ≤ 4
• Modified Fisher Grade I-IV
• Glasgow Coma Scale (GCS) ≥ 7 following External Ventricular Drain (EVD) placement if indicated
• First dose of drug can be administered within 24 hours of symptom onset
• Functional independence prior to SAH, Modified Rankin Scale (mRS) ≤ 1
• Informed consent obtained by patient or legal authorized representative (LAR)

Exclusion criteria

• Previous hypersensitivity to or treatment with deferoxamine
• Presence of giant aneurysm (>25 mm in size)
• Known severe iron deficiency anemia, Hemoglobin (Hgb) g/dl ≤ 7 or transfusion dependent
• Irreversibly impaired brainstem function
• Abnormal renal function, Serum Creatinine> 2 mg/dL
• Pre-existing severe disability, mRS ≥ 2
• Coagulopathy, including use of anti-platelet or anticoagulant drugs
• Known severe hearing loss
• Patients with significant respiratory disease such as chronic obstructive pulmonary disease, pulmonary fibrosis, or on home oxygen (O2)
• Taking iron supplements containing > 325 mg of ferrous iron
• Pregnancy
• Life expectancy less than 90 days due to co-morbidities
• Concurrent participation in another research protocol for investigation of another experimental therapy, though observational studies are allowed
• Prior history of hepatic dysfunction
• Known cytopenia (platelets < 50,000, Absolute neutrophil count < 500)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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120 participants in 3 patient groups, including a placebo group

Deferoxamine lower dose

Experimental group

Description:

Deferoxamine 32 Milligram Per Kilogram (mg/kg)

Treatment:

Drug: Deferoxamine

Deferoxamine higher dose

Experimental group

Description:

Deferoxamine 48 mg/kg

Treatment:

Drug: Deferoxamine

Placebo

Placebo Comparator group

Description:

normal saline

Treatment:

Drug: Placebo