Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)

Официальное название

Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (DISH)

Обзор

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.

Вмешательства

• Препарат Deferoxamine
  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.
• Препарат Placebo
  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.

Первичные конечные точки

• Utility-weighted modified Rankin Scale (UW-mRS) at 6 months [Срок оценки: 6 months (after hospital discharge)]

Вторичные конечные точки (6)

• Montreal Cognitive Assessment (MOCA) [Срок оценки: At discharge from hospital (approximately 3-4 weeks)]
• Montreal Cognitive Assessment (MOCA) [Срок оценки: 6 months (after hospital discharge)]
• Percentage of patients requiring permanent cerebrospinal fluid (CSF) diversion due to hydrocephalus at 6 months [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: infusion days 1-3]
• Incidence of delayed cerebral ischemia/vasospasm [Срок оценки: up to 14 days after aSAH]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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
• Known cytopenia (platelets < 50,000, Absolute neutrophil count < 500)
• Current use of prochlorperazine
• History of severe psychiatric disorder

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Michigan — Ann Arbor

Идентификаторы

NCT: NCT04566991 · HUM00163868

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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