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| ID | Type | Description | Link |
|---|---|---|---|
| 1R44NS063485-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nitrite | Experimental | Continuous intravenous infusion of Sodium Nitrite |
|
| Vehicle control | Placebo Comparator | Continuous intravenous infusion of saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium nitrite | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Efficacy of 14 Day Infusion of Sodium Nitrite |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Edward Oldfield, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Virginia Health System Medical Center | Charlottesville | Virginia | 22903 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23706046 | Derived | 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. |
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Patients underwent neurosurgical repair of their subarachnoid hemorrhage prior to study recruitment and assignment.
Patients admitted to University of Virginia Medical Center for the treatment of subarachnoid hemorrhage were screened for possible recruitment into this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vehicle Control | Nitrite : 14 day continuous infusion of a vehicle control infusion |
| FG001 | Nitrite 32 Nmol/Min/kg | 14 day continuous infusion of sodium nitrite 32 nmol/min/kg |
| FG002 | Nitrite 48 Nmol/Min/kg | 14 day continuous infusion of sodium nitrite 48 nmol/min/kg |
| FG003 | Nitrite 64 Nmol/Min/kg | 14 day continuous infusion of sodium nitrite 64 nmol/min/kg |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | 32 Nmol/Min/kg | Sodium nitrite : 14 day continuous infusion 32 nmol/min/kg |
| BG001 | Vehicle Control | Nitrite : 14 day continuous infusion of a vehicle control infusion |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per protocol | Posted | Mean | Standard Deviation | micromol/L | multiple time points up to the end of day 14 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nitrite | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abscess | Infections and infestations | Systematic Assessment | Abdominal abscess (secondary to percutaneous endoscopic gastrostomy tube dislodgement) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Edward Oldfield | University of Virginia Medical Center | (434) 982-0059 | EHO4U@hscmail.mcc.virginia.edu |
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| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| D002532 | Intracranial Aneurysm |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D009573 | Nitrites |
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
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| Saline | Drug | 14 day continuous infusion of a vehicle control infusion |
|
|
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 |
| BG002 | 48 Nmol/Min/kg | Sodium nitrite: 14 day continuous infusion 48 nmol/min/kg |
| BG003 | 64 Nmol/Min/kg | Sodium nitrite: 14 day continuous infusion 64 nmol/min/kg |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| 48 Nmol/Min/kg |
Sodium nitrite : 14 day continuous infusion of 48 nmol/min/kg |
| OG002 | 32 Nmol/Min/kg | Sodium nitrite : 14 day continuous infusion of 32 nmol/min/kg |
|
|
| 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 | Posted | Count of Participants | Participants | No | 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). | Posted | Count of Participants | Participants | No | 14 days |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Vehicle Control | Nitrite : 14 day continuous infusion of a vehicle control infusion | 2 | 9 | 0 | 9 |
|
| Death | Nervous system disorders | Systematic Assessment | Stroke progression (withdrawal of life support) |
|
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| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020765 | Intracranial Arterial Diseases |
| D000783 | Aneurysm |
| D017670 |
| Sodium Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |