Deferoxamine to Prevent Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Deferoxamine: An Emerging Therapy to Prevent Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

The investigators will test the central hypothesis that DFO treatment after SAH may improve cerebrovascular regulation, mitigate ischemic neural injury, and serve as an effective neuroprotectant against delayed ischemic injury after SAH.

Study Overview

• Status: Terminated
• Conditions: Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: desferrioxamine (DFO); Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of spontaneous SAH
• impaired cerebral autoregulation on day 2-4 post SAH

Exclusion Criteria:

• traumatic SAH
• other central neurological disorders such as tumors, known prior stroke, hemorrhage or vascular malformations
• pregnancy
• severe renal disease or anuria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Desferrioxamine (DFO); DFO (20mg/kg/hr) in normal saline IV for 4 hours for 5 consecutive days	Drug: desferrioxamine (DFO); DFO (20mg/kg/hr) in normal saline for 4 hours for 5 consecutive days; Other Names: deferoxamine, desferal, DFO, deferoxamine mesylate
Placebo Comparator: placebo; normal saline IV for 4 hours for 5 consecutive days	Drug: placebo; normal saline IV for 4 hours for 5 consecutive days; Other Names: normal saline NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
delayed cerebral ischemia (DCI)	DCI will be defined radiographically as any cerebral infarct on the latest CT scan that was seen within 6 weeks after SAH or before discharge or death, that was not present on admission scan or on the CT scan done within 24 to 48 hours after any aneurysmal treatment procedures. All head CT scans will be reviewed for DCI ascertainment by neuroradiologists blinded to the clinical and TCD data using the standardized protocol.	6 weeks post hemorrhage

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcome at discharge	Clinical outcome at discharge will be assessed using modified Rankin Scale (mRS) as a global functional status. The modified Rankin scale evaluates global disability and handicap; scores range from 0 (no symptoms or disability) to 6 (death). Good mRS will be defined as score of ≤ 2.	patient's discharge date, which averages 3-4 weeks post hemorrhage

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrovascular function (i.e., cerebral autoregulation)	Spectral analysis of the relationship between arterial pressure and blood flow velocity in the bilateral middle cerebral arteries (measured via TCD). Autoregulation will be assessed from the phase and gain of the transfer function. Phase shift reflects the temporal difference between cerebral flow velocity fluctuations with respect to arterial pressure fluctuations. When the fluctuations of both flow and pressure are almost synchronous, the phase shift approaches zero, reflecting impaired cerebral autoregulation. Transfer function gain reflects the magnitude of transmission of arterial pressure fluctuations to cerebral blood flow velocity fluctuations. Lower gain, particularly in the low frequency (< 0.1 Hz) range, is reflective of more effective cerebral autoregulation. Coherence reflects the degree of linear dependence between pressure and flow fluctuations. Thus, it provides a measure of validity of the metrics (gain and phase) derived from the linear transfer function.	5 days after initiation of study drug

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Dr. Jeffrey Thomas Stroke Shield Foundation
• Investigators: Principal Investigator: Farzaneh A Sorond, MD, PhD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Van der Loo LE, Aquarius R, Teernstra O, Klijn K, Menovsky T, van Dijk JMC, Bartels R, Boogaarts HD. Iron chelators for acute stroke. Cochrane Database Syst Rev. 2020 Nov 24;11(11):CD009280. doi: 10.1002/14651858.CD009280.pub3.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: August 6, 2014
• First Submitted That Met QC Criteria: August 12, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Estimate): July 21, 2015
• Last Update Submitted That Met QC Criteria: July 17, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: SAH; subarachnoid hemorrhage; cerebral autoregulation; delayed cerebral ischemia; DFO
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infarction; Stroke; Brain Infarction; Intracranial Hemorrhages; Brain Ischemia; Ischemia; Hemorrhage; Cerebral Infarction; Subarachnoid Hemorrhage; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferoxamine
• Other Study ID Numbers: 2014P001400