Intravenous Nitrite Infusion for Reversal of Cerebral Vasospasm After Subarachnoid Hemorrhage

• ClinicalTrials.gov Identifier: NCT02176837
• Recruitment Status: Terminated
• First Posted: June 27, 2014
• Results First Posted: February 8, 2018
• Last Update Posted: March 30, 2018
• Sponsor: Hope Pharmaceuticals
• Information provided by (Responsible Party): Hope Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Subarachnoid Hemorrhage	Drug: Sodium Nitrite	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Intravenous Nitrite Infusion for Reversal of Cerebral Vasospasm After Subarachnoid Hemorrhage From a Cerebral Aneurysm
• Study Start Date: June 2014
• Actual Primary Completion Date: January 15, 2017
• Actual Study Completion Date: January 15, 2017

Arms and Interventions

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 Name: Sodium Nitrite Injection 300 mg/10 mL

Outcome Measures

Primary Outcome Measures :

1. Cerebral Vasospasm [ Time Frame: 180 minutes ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Virginia

University of Virginia Medical Center

Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

Hope Pharmaceuticals

Investigators

• Principal Investigator: Kenny Liu, MD; University of Virginia Medical Center, Department of Neurosurgery

More Information

• Responsible Party: Hope Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02176837
• Other Study ID Numbers: SN-03-01
• First Posted: June 27, 2014
• Results First Posted: February 8, 2018
• Last Update Posted: March 30, 2018
• Last Verified: March 2018

Keywords provided by Hope Pharmaceuticals:

subarachnoid hemorrhage; vasospasm; nitrite; sodium nitrite

Additional relevant MeSH terms:

Subarachnoid Hemorrhage; Vasospasm, Intracranial; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases