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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deferoxamine lower dose | Experimental | Deferoxamine 32 Milligram Per Kilogram (mg/kg) |
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| Deferoxamine higher dose | Experimental | Deferoxamine 48 mg/kg |
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| Placebo | Placebo Comparator | normal saline |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Montreal Cognitive Assessment (MOCA) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sravanthi Koduri | Contact | 734-647-7960 | skoduri@med.umich.edu | |
| Aditya Pandey, MD | Contact | 734-615-2763 | adityap@umich.edu |
| Name | Affiliation | Role |
|---|---|---|
| Aditya Pandey, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Recruiting | Ann Arbor | Michigan | 48109 | United States |
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| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D003676 | Deferoxamine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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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.
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| 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. |
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| At discharge from hospital (approximately 3-4 weeks) |
| Montreal Cognitive Assessment (MOCA) | 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. | 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) | 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 |
| Incidence of delayed cerebral ischemia/vasospasm | This is based on radiographic evidence on computed tomography angiogram and clinical correlation with neurologic exam. | up to 14 days after aSAH |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006880 |
| Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |