Deferoxamine to Prevent Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT02216513

Collaborator

Dr. Jeffrey Thomas Stroke Shield Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Subarachnoid Hemorrhage	Drug: desferrioxamine (DFO) Drug: placebo	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2014

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jul 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

delayed cerebral ischemia (DCI) [6 weeks post hemorrhage]
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.

Secondary Outcome Measures

Clinical outcome at discharge [patient's discharge date, which averages 3-4 weeks post hemorrhage]
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.

Other Outcome Measures

Cerebrovascular function (i.e., cerebral autoregulation) [5 days after initiation of study drug]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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