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Completed

NCT Number: NCT00873015

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.

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Key information

Conditions

Subarachnoid Hemorrhage Aneurysm Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Hemorrhage Intracranial Aneurysm Intracranial Arterial Diseases Intracranial Hemorrhages Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Virginia Health System Medical Center

Charlottesville, Virginia, 22903, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Ruptured cerebral aneurysm

Exclusion criteria

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

Treatment and study plan

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

Other names: Sodium Nitrite Injection NDC 60267-311-10

Saline

Drug

14 day continuous infusion of a vehicle control infusion

Other names: Sterile saline

Primary outcomes

  1. Mean Plasma Nitrite Concentration (Micromol/L)

    Time frame: multiple time points up to the end of day 14

    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 outcomes

  1. Safety of a 14 Day Infusion of Sodium Nitrite

    Time frame: 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

  2. Efficacy of 14 Day Infusion of Sodium Nitrite

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

Hope Pharmaceuticals

Industry

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

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

Important dates

Study start
2010
Primary completion
2010
Study completion
2012
First posted
Apr 1, 2009
Registry last updated
May 21, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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