Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (DISH)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Utility-weighted modified Rankin Scale (UW-mRS) at 6 months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Deferoxamine lower dose
Deferoxamine 32 Milligram Per Kilogram (mg/kg)
干预措施: Deferoxamine (Drug)
Deferoxamine higher dose
Deferoxamine 48 mg/kg
干预措施: Deferoxamine (Drug)
Placebo
normal saline
干预措施: Placebo (Drug)
结局指标
主要结局
Utility-weighted modified Rankin Scale (UW-mRS) at 6 months
时间窗: 6 months (after hospital discharge)
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.
次要结局
- 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)
- 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)
- Incidence of delayed cerebral ischemia/vasospasm(up to 14 days after aSAH)
研究者
Aditya S. Pandey, MD
Associate Professor of Neurosurgery and Associate Professor of Radiology
University of Michigan