Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm

NCT ID: NCT00873015

Last Updated: 2020-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2012-08-31

Brief 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.

Detailed 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.

Conditions

Subarachnoid Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Nitrite

Continuous intravenous infusion of Sodium Nitrite

Group Type: EXPERIMENTAL

Sodium nitrite

Intervention Type: 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

Vehicle control

Continuous intravenous infusion of saline

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

14 day continuous infusion of a vehicle control infusion

Interventions

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

Intervention Type: DRUG

Saline

14 day continuous infusion of a vehicle control infusion

Intervention Type: DRUG

Other Intervention Names

Sodium Nitrite Injection NDC 60267-311-10; Sterile saline

Eligibility Criteria

Inclusion Criteria

• Ruptured cerebral aneurysm

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Hope Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward Oldfield, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia Health System Medical Center

Charlottesville, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 23706046 (View on PubMed)

Other Identifiers

1R44NS063485-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

14024

Identifier Type: -

Identifier Source: org_study_id