Clinical trial NCT04566991: Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)
Official title: Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (DISH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Aneurysmal Subarachnoid Hemorrhage
Keywords: Deferoxamine
Placebo
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Michigan Medicine PKUHSC Joint Institute for Translational & Clinical Research
First posted: 2020-09-28
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Utility-weighted modified Rankin Scale (UW-mRS) at 6 months
timeFrame: 6 months (after hospital discharge)
Secondary outcomes:
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: At discharge from hospital (approximately 3-4 weeks)
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: 6 months (after hospital discharge)
measure: Percentage of patients requiring permanent cerebrospinal fluid (CSF) diversion due to hydrocephalus at 6 months
timeFrame: 6 months
measure: 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)
timeFrame: up to 48 hours after day 3 infusion
measure: 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
timeFrame: infusion days 1-3
measure: Incidence of delayed cerebral ischemia/vasospasm
timeFrame: up to 14 days after aSAH
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Beijing
country: China
facility: Peking University Health Science Center
state: Beining
Study officials:
affiliation: University of Michigan
name: Aditya Pandey, MD
role: PRINCIPAL_INVESTIGATOR
References: