Intravenous Nitrite Infusion for Reversal of Cerebral Vasospasm After Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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The hypothesis is that intravenous infusion of sodium nitrite is safe and effective for the reversal of cerebral vasospasm after subarachnoid hemorrhage in patients with a cerebral aneurysm.

Detailed Description
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This is a pilot single center, open-labeled study. Patients with subarachnoid hemorrhage admitted to the hospital and who meet entry criteria will be offered enrollment into the study. The patients will be enrolled promptly after detection of the presence of cerebral vasospasm. Subjects will receive sodium nitrite infusion. One dose cohort is planned, 64 nmol/min/kg sodium nitrite (0.1325 mg/hour/kg; 0.0442 ml/hour/kg at a concentration of 3mg/ml).

Official Title
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Evaluation of Intravenous Nitrite Infusion for Reversal of Cerebral Vasospasm After Subarachnoid Hemorrhage From a Cerebral Aneurysm

Conditions
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Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Sodium Nitrite


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained from a patient or legal representative before enrollment; Admission to hospital following subarachnoid hemorrhage; Aneurysm confirmed by digital subtraction angiography or CT-angiography after admission; Development of the clinical symptoms and /or signs of cerebral vasospasm and CT-angiography results warranting cerebral angiography. Exclusion Criteria: Rupture of a fusiform, traumatic, or mycotic aneurysm; Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast feeding; Methemoglobin > 2% History of sickle cell disease, thalassemia, or other hemoglobinopathy; Anemia with hemoglobin level less than 6 g/dL; Significant acute or chronic concomitant diseases (including renal, hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary embolism) that would be inconsistent with survival for at least 6 months; History of allergy to nitrites or allergy to other substances that could interfere with nitrite metabolism, within 30 days before screening; History of red blood cell glucose-6-phosphate dehydrogenase (G6PD)deficiency; Treatment with allopurinol, a medication that could interfere with nitrite metabolism, within 30 days before screening; Other investigational drug within the past 30 days; other cerebral injury within the past 30 days including previous subarachnoid hemorrhage, stroke, transient ischemic attacks (TIA), concussion, head trauma, cranial surgery, radiation therapy to the head.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Nitrite<br>One dose cohort is planned, 64 nmol/min/kg sodium nitrite (0.1325 mg/hour/kg; 0.0442 ml/hour/kg at a concentration of 3mg/ml). | Drug: Sodium Nitrite<br>* Subjects will receive continuous intravenous infusion of study drug for 7 days at a dose of 64 nmol/min/kg. The infusion will begin shortly after angiographic demonstration of cerebral vasospasm and will be for 7 days unless side effects of the drug dictate stopping the infusion.<br>* Other names: Sodium Nitrite Injection 300 mg/10 mL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Vasospasm | Cerebral digital subtraction angiographies will be reviewed at at least 2 time points, including at the time of diagnosis of angiographic vasospasm immediately before treatment with nitrite and after up to 180 minutes of nitrite infusion. Radiographs will be compared to determine whether increased flow of radiographic dye is visualized following initiation of nitrite infusion. | 180 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subarachnoid hemorrhage, vasospasm, nitrite, sodium nitrite