Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)

Phase 2

Recruiting

Brief Summary: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	normal saline
Deferoxamine lower dose	Deferoxamine	Deferoxamine 32 Milligram Per Kilogram (mg/kg)
Deferoxamine higher dose	Deferoxamine	Deferoxamine 48 mg/kg

Primary Outcome Measures

Name	Time	Method
Utility-weighted modified Rankin Scale (UW-mRS) at 6 months	6 months (after hospital discharge)	Overall a Bayesian, longitudinal model will be used, this will be adjusted for baseline expected 6 month mRS using the FRESH score. At baseline, the expected 6 month UW-mRS (based on prognostic variables such as age and Hunt Hess) will be entered as the first value for the patient. Therefore, patients with greater severity at baseline, who achieve excellent outcomes will contribute a larger treatment effect. Similarly, patients with greater severity who have disability, but perform better than expected can still contribute useful information.

Secondary Outcome Measures

Name	Time	Method
Partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio (worst value for each parameter for each day of infusion, and 48 hours after end of infusion)	up to 48 hours after day 3 infusion	Worst value for each parameter for each day of infusion, and 48 hours after end of infusion.
To estimate the proportion of non-intubated participants at each dose who experience intubation or initiation of non-invasive positive pressure ventilation during the DFO	infusion days 1-3
Montreal Cognitive Assessment (MOCA)	6 months (after hospital discharge)	Montreal cognitive assessment is a rapid sensitive screening tool for assessment of impaired cognitive function. The main domains of MoCA scale include attention, executive functions, memory, language, attention, naming, orientation, and visual-spatial ability. The total score is 30 points. A score of 25 points or less indicated impaired cognitive function. For patients with less than 12 years of education, one point was added to the total score.
Percentage of patients requiring permanent cerebrospinal fluid (CSF) diversion due to hydrocephalus at 6 months	6 months
Incidence of delayed cerebral ischemia/vasospasm	up to 14 days after aSAH	This is based on radiographic evidence on computed tomography angiogram and clinical correlation with neurologic exam.

Locations (2): University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Peking University Health Science Center
🇨🇳
Beijing, Beining, China