Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)

NCT04566991 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HUM00163868
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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. 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.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

Deferoxamine; Placebo

Outcome Measures

Primary Outcomes (1)

• Utility-weighted modified Rankin Scale (UW-mRS) at 6 months

  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.

  6 months (after hospital discharge)

Secondary Outcomes (6)

• Montreal Cognitive Assessment (MOCA)

  At discharge from hospital (approximately 3-4 weeks)

• Montreal Cognitive Assessment (MOCA)

  6 months (after hospital discharge)

• Percentage of patients requiring permanent cerebrospinal fluid (CSF) diversion due to hydrocephalus at 6 months

  6 months

• 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

• 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

Study Arms (3)

Deferoxamine lower dose

EXPERIMENTAL

Deferoxamine 32 Milligram Per Kilogram (mg/kg)

Drug: Deferoxamine

Deferoxamine higher dose

EXPERIMENTAL

Deferoxamine 48 mg/kg

Drug: Deferoxamine

Placebo

PLACEBO COMPARATOR

normal saline

Drug: Placebo

Interventions

Deferoxamine DRUG

There will be 3 doses given to the patients days 1-3. Dose will be given intravenous with a fixed rate of 7.5 milligram per kilogram per hour (mg/kg/hr). The second dose will be given 24 hours after the first dose, and the third dose will be given 48 hours after the initial dose. Patients will be randomized to 32 mg/kg or 48 mg/kg of Deferoxamine.

Also known as: Desferal

Deferoxamine higher dose; Deferoxamine lower dose

Placebo DRUG

There will be 3 doses given to the patients days 1-3. Dose will be given intravenous with a fixed rate of 7.5 mg/kg/hr. The second dose will be given 24 hours after the first dose, and the third dose will be given 48 hours after the initial dose.

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• Chronic pulmonary disease that limits basic activities of daily living at baseline, or requires the use of home oxygen.
• Acute pulmonary disease with the need for any of the following - in a 72 hour period prior to enrollment: \>4L/minute nasal cannula (or equivalent O2 delivery via face mask/ tent), heated-high flow nasal cannula, noninvasive positive pressure ventilation, and in intubated patients FiO2\>45% or positive end-expiratory pressure (PEEP) \> 8cmH2O. This does not include the use of supplemental oxygen in any form for pre-oxygenation, apneic oxygenation, or peri-procedural support alone.
• Taking iron supplements containing \> 325 mg of ferrous iron
• Pregnancy or nursing
• 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

Sponsors & Collaborators

• Aditya S. Pandey, MD: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Deferoxamine; Saline Solution

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Aditya Pandey, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sravanthi Koduri

CONTACT

734-647-7960; skoduri@med.umich.edu

Aditya Pandey, MD

CONTACT

734-615-2763; adityap@umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: All patients and investigators who will be directly involved in the care of these patients or in data analysis will be blinded to randomization status.This trial uses a Bayesian adaptive randomization protocol, where there are three groups that patients will be randomized into: placebo, DFO 32 mg/kg and DFO 48 mg/kg. The first 50 patients will be randomized evenly into each of these groups. The randomization ratio will be adjusted based on the design report after 50 subjects and then every 10 patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurosurgery and Associate Professor of Radiology

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 28, 2020
• Study Start: March 20, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)