Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The purpose of the study is to examine the safety of a 14 day infusion of sodium nitrite, and to study the pharmacokinetics of nitrite, during a 14 day infusion in patients with ruptured cerebral aneurysms.

Condition or disease	Intervention/treatment	Phase
Subarachnoid Hemorrhage	Drug: Sodium nitrite; Drug: Saline	Phase 2

Detailed Description:

Intravenous sodium nitrite has been shown to prevent and to reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). This was a Phase IIA dose escalation study of sodium nitrite to determine its safety in patients with aneurysmal SAH and to establish its pharmacokinetics during a 14 day infusion.

Sodium nitrite was delivered intravenously for 14 days in 18 patients with SAH from a ruptured cerebral aneurysm using a dose escalation scheme in three cohorts of 6 patients each (3 nitrite, 3 saline), with a maximum dose of 64 nmol/min/kg. Sodium nitrite blood levels were frequently sampled and measured using mass spectroscopy and blood methemoglobin levels were continuously monitored using a pulse oximeter.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	19 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
Official Title:	Safety and Pharmacokinetic Evaluation of Sodium Nitrite Injection for the Prevention of Post-Subarachnoid Hemorrhage Induced Vasospasm
Study Start Date :	April 2010
Actual Primary Completion Date :	November 2010
Actual Study Completion Date :	August 2012

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Nitrite; Continuous intravenous infusion of Sodium Nitrite	Drug: Sodium nitrite; 14 day continuous infusion of one of 3 escalating doses of sodium nitrite: 32 nmol/min/kg, 48 nmol/min/kg, or 64 nmol/min/kg; Other Name: Sodium Nitrite Injection NDC 60267-311-10
Placebo Comparator: Vehicle control; Continuous intravenous infusion of saline	Drug: Saline; 14 day continuous infusion of a vehicle control infusion; Other Name: Sterile saline

Outcome Measures

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Primary Outcome Measures :

1. Mean Plasma Nitrite Concentration (Micromol/L) [ Time Frame: multiple time points up to the end of day 14 ]
   Samples for pharmacokinetic analysis were collected from subjects treated with sodium nitrite at -15, -5, 0, 10, 30, 60, and 90 minutes after starting nitrite infusion and then at 2, 4, 6, 8, 12, 24, and every 24 hours after starting nitrite infusion. The sample at the time of starting the infusion was considered to be the time 0 sample. On study day 14 additional blood samples were collected at 0, 10, 30, 60, and 90 minutes and at 2, 4, 6, 8, and 12 hours after stopping nitrite infusion. Blood samples were analyzed for nitrite levels using mass spectroscopy.

Secondary Outcome Measures :

1. Safety of a 14 Day Infusion of Sodium Nitrite [ Time Frame: 14 days ]
2. Efficacy of 14 Day Infusion of Sodium Nitrite [ Time Frame: 14 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Ruptured cerebral aneurysm

Exclusion Criteria:

• Pregnancy, sickle cell disease, G6PD deficiency, anticoagulant therapy

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Virginia
University of Virginia Health System Medical Center
Charlottesville, Virginia, United States, 22903

Sponsors and Collaborators

Hope Pharmaceuticals

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Edward Oldfield, MD	University of Virginia

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Oldfield EH, Loomba JJ, Monteith SJ, Crowley RW, Medel R, Gress DR, Kassell NF, Dumont AS, Sherman C. Safety and pharmacokinetics of sodium nitrite in patients with subarachnoid hemorrhage: a phase IIa study. J Neurosurg. 2013 Sep;119(3):634-41. doi: 10.3171/2013.3.JNS13266. Epub 2013 May 24.

Responsible Party:	Hope Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00873015 History of Changes
Other Study ID Numbers:	14024; 1R44NS063485-01 ( U.S. NIH Grant/Contract )
First Posted:	April 1, 2009
Results First Posted:	July 16, 2013
Last Update Posted:	June 7, 2017
Last Verified:	May 2017

Keywords provided by Hope Pharmaceuticals:

Cerebral aneurysm; Subarachnoid hemorrhage; Nitrite

Additional relevant MeSH terms:

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