Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm

May 12, 2020 updated by: Hope Pharmaceuticals

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

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health System Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ruptured cerebral aneurysm

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nitrite
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 Names:
  • Sodium Nitrite Injection NDC 60267-311-10
Placebo Comparator: Vehicle control
Continuous intravenous infusion of saline
Drug: Saline
14 day continuous infusion of a vehicle control infusion
Other Names:
  • Sterile saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
multiple time points up to the end of day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
14 days
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).
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hope Pharmaceuticals

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Edward Oldfield, MD, University of Virginia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

March 31, 2009

First Submitted That Met QC Criteria

March 31, 2009

First Posted (Estimate)

April 1, 2009

Study Record Updates

Last Update Posted (Actual)

May 21, 2020

Last Update Submitted That Met QC Criteria

May 12, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14024
  • 1R44NS063485-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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