Intravenous Nitrite Infusion for Reversal of Cerebral Vasospasm After Subarachnoid Hemorrhage

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

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.

Study Overview

• Status: Terminated
• Conditions: Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Sodium Nitrite

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Nitrite; 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; 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.; Other Names: Sodium Nitrite Injection 300 mg/10 mL

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hope Pharmaceuticals
• Investigators: Principal Investigator: Kenny Liu, MD, University of Virginia Medical Center, Department of Neurosurgery

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): January 15, 2017
• Study Completion (Actual): January 15, 2017

Study Registration Dates

• First Submitted: February 19, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 27, 2014

Study Record Updates

• Last Update Posted (Actual): March 30, 2018
• Last Update Submitted That Met QC Criteria: March 4, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: subarachnoid hemorrhage; vasospasm; sodium nitrite; nitrite
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Vasospasm, Intracranial
• Other Study ID Numbers: SN-03-01