Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm
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.
|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|
- 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.
- 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 ]
|Study Start Date:||April 2010|
|Study Completion Date:||August 2012|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
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
14 day continuous infusion of a vehicle control infusion
Other Name: Sterile saline
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.
|United States, Virginia|
|University of Virginia Health System Medical Center|
|Charlottesville, Virginia, United States, 22903|
|Principal Investigator:||Edward Oldfield, MD||University of Virginia|