Trial Outcomes & Findings for Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm (NCT NCT00873015)

NCT ID: NCT00873015

Last Updated: 2020-05-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 19 participants
• Primary outcome timeframe: multiple time points up to the end of day 14
• Results posted on: 2020-05-21

Participant Flow

Patients admitted to University of Virginia Medical Center for the treatment of subarachnoid hemorrhage were screened for possible recruitment into this study.

Patients underwent neurosurgical repair of their subarachnoid hemorrhage prior to study recruitment and assignment.

Participant milestones

Measure	Vehicle Control Nitrite : 14 day continuous infusion of a vehicle control infusion	Nitrite 32 Nmol/Min/kg 14 day continuous infusion of sodium nitrite 32 nmol/min/kg	Nitrite 48 Nmol/Min/kg 14 day continuous infusion of sodium nitrite 48 nmol/min/kg	Nitrite 64 Nmol/Min/kg 14 day continuous infusion of sodium nitrite 64 nmol/min/kg
Overall Study STARTED	9	4	3	3
Overall Study COMPLETED	9	3	3	3
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Measure	Vehicle Control Nitrite : 14 day continuous infusion of a vehicle control infusion	Nitrite 32 Nmol/Min/kg 14 day continuous infusion of sodium nitrite 32 nmol/min/kg	Nitrite 48 Nmol/Min/kg 14 day continuous infusion of sodium nitrite 48 nmol/min/kg	Nitrite 64 Nmol/Min/kg 14 day continuous infusion of sodium nitrite 64 nmol/min/kg
Overall Study Withdrawal by Subject	0	1	0	0

Baseline Characteristics

Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm

Baseline characteristics by cohort

Measure	32 Nmol/Min/kg n=4 Participants Sodium nitrite : 14 day continuous infusion 32 nmol/min/kg	Vehicle Control n=9 Participants Nitrite : 14 day continuous infusion of a vehicle control infusion	48 Nmol/Min/kg n=3 Participants Sodium nitrite: 14 day continuous infusion 48 nmol/min/kg	64 Nmol/Min/kg n=3 Participants Sodium nitrite: 14 day continuous infusion 64 nmol/min/kg	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	18 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Continuous	50 years STANDARD_DEVIATION 10 • n=5 Participants	52 years STANDARD_DEVIATION 18.3 • n=7 Participants	50 years STANDARD_DEVIATION 5 • n=5 Participants	58 years STANDARD_DEVIATION 7 • n=4 Participants	51 years STANDARD_DEVIATION 9.9 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment United States	4 participants n=5 Participants	9 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	19 participants n=21 Participants

PRIMARY outcome

Timeframe: multiple time points up to the end of day 14

Population: Per protocol

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.

Outcome measures

Measure	64 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 64 nmol/min/kg	48 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 48 nmol/min/kg	32 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 32 nmol/min/kg	Placebo Intravenous saline administration
Mean Plasma Nitrite Concentration (Micromol/L)	4.2 micromol/L Standard Deviation 0.3	4.3 micromol/L Standard Deviation 0.4	2.6 micromol/L Standard Deviation 0.3	—

SECONDARY outcome

Timeframe: 14 days

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

Outcome measures

Measure	64 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 64 nmol/min/kg	48 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 48 nmol/min/kg	32 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 32 nmol/min/kg	Placebo n=9 Participants Intravenous saline administration
Safety of a 14 Day Infusion of Sodium Nitrite	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days

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).

Outcome measures

Measure	64 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 64 nmol/min/kg	48 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 48 nmol/min/kg	32 Nmol/Min/kg n=3 Participants Sodium nitrite : 14 day continuous infusion of 32 nmol/min/kg	Placebo n=9 Participants Intravenous saline administration
Efficacy of 14 Day Infusion of Sodium Nitrite	1 Participants	1 Participants	0 Participants	3 Participants

Adverse Events

Nitrite

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vehicle Control

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nitrite n=9 participants at risk 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	Vehicle Control n=9 participants at risk Nitrite : 14 day continuous infusion of a vehicle control infusion
Infections and infestations Abscess	0.00% 0/9	11.1% 1/9 • Number of events 1
Nervous system disorders Death	0.00% 0/9	11.1% 1/9 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Dr. Edward Oldfield

University of Virginia Medical Center

Phone: (434) 982-0059

Email: EHO4U@hscmail.mcc.virginia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place