Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm

This study has been completed.

Sponsor:

Collaborator:

National Institute of Neurological Disorders and Stroke (NINDS)

Information provided by (Responsible Party):

Hope Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00873015

First received: March 31, 2009

Last updated: July 28, 2013

Last verified: July 2013

History of Changes

Purpose

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	Intervention	Phase
Subarachnoid Hemorrhage.	Drug: Sodium nitrite Drug: Saline	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Safety and Pharmacokinetic Evaluation of Sodium Nitrite Injection for the Prevention of Post-Subarachnoid Hemorrhage Induced Vasospasm

Resource links provided by NLM:

MedlinePlus related topics: Bleeding

Drug Information available for: Sodium nitrite

U.S. FDA Resources

Further study details as provided by Hope Pharmaceuticals:

Primary Outcome Measures:

Mean Plasma Nitrite Concentration (Micromol/L) [ Time Frame: multiple time points up to the end of day 14 ] [ Designated as safety issue: Yes ]
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:

Safety of a 14 Day Infusion of Sodium Nitrite [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
Efficacy of 14 Day Infusion of Sodium Nitrite [ Time Frame: 14 days ] [ Designated as safety issue: No ]


Enrollment:	19
Study Start Date:	April 2010
Study Completion Date:	August 2012
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Ruptured cerebral aneurysm

Exclusion Criteria:

Pregnancy, sickle cell disease, G6PD deficiency, anticoagulant therapy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00873015

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

No publications provided by Hope Pharmaceuticals

Additional 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
Study First Received:	March 31, 2009
Results First Received:	January 26, 2013
Last Updated:	July 28, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hope Pharmaceuticals:


Cerebral aneurysm Subarachnoid hemorrhage Nitrite

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on February 27, 2015

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