Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm

Subarachnoid Hemorrhage Clinical Trial

Official title:

Safety and Pharmacokinetic Evaluation of Sodium Nitrite Injection for the Prevention of Post-Subarachnoid Hemorrhage Induced Vasospasm

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00873015
• Other study ID #: 14024
• Secondary ID: 1R44NS063485-01
• Status: Completed
• Phase: Phase 2
• Start date: April 2010
• Est. completion date: August 2012

Study information

• Verified date: May 2020
• Source: Hope Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 2012
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Ruptured cerebral aneurysm

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage

Intervention

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
• Saline
14 day continuous infusion of a vehicle control infusion

Locations

Country	Name	City	State
United States	University of Virginia Health System Medical Center	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Hope Pharmaceuticals	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Plasma Nitrite Concentration (Micromol/L)	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.	multiple time points up to the end of day 14
Secondary	Safety of a 14 Day Infusion of Sodium Nitrite	Development of methemoglobin > 5% or hypotension (systolic arterial blood pressure < 90 mm Hg for more than 15 minutes or < 80 mm Hg) during infusion of sodium nitrite	14 days
Secondary	Efficacy of 14 Day Infusion of Sodium Nitrite	Development of vasospasm as documented by onset of neurologic symptoms and documentation of narrowing of vessel(s) on cerebral angiogram. Potential clinical vasospasm was evaluated as appropriate, based on the development of focal neurological deficits that suggested cerebral ischemia (such as hemiparesis and speech deficit) or global neurological deficit (altered level of consciousness) that could not be attributed to other etiologies (such as metabolic abnormalities, intracerebral hemorrhage, and hydrocephalus).	14 days