Subarachnoid HemorrhagePhase 2NCT00873015
Safety and Pharmacokinetic Evaluation of Nitrite for Prevention of Cerebral Vasospasm
A Phase 2 study testing Sodium nitrite and Saline in people with Subarachnoid Hemorrhage, run by Hope Pharmaceuticals at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Subarachnoid Hemorrhage
- What is being tested?
- Sodium nitrite and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ruptured cerebral aneurysm
Who cannot join
- Pregnancy, sickle cell disease, G6PD deficiency, anticoagulant therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Health System Medical Center
Charlottesville, Virginia, 22903
About this study
Official title: 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.
Read the 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
- Being tested
- Sodium nitrite, Saline
- Keywords
- Cerebral aneurysm, Subarachnoid hemorrhage, Nitrite
- Medical subject headings
- Subarachnoid Hemorrhage, Intracranial Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium nitriteDrug
Also called Sodium Nitrite Injection NDC 60267-311-10
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
SalineDrug
Also called Sterile saline
14 day continuous infusion of a vehicle control infusion
| Study group | Role | What they receive |
|---|---|---|
| Nitrite | Experimental | Continuous intravenous infusion of Sodium Nitrite Receives: Drug: Sodium nitrite |
| Vehicle control | Placebo comparator | Continuous intravenous infusion of saline Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: multiple time points up to the end of day 14
Secondary outcomes (2)
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
Measured: 14 days
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).
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2009 (estimated)
- Study startApr 2010
- Primary completionNov 2010
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hope Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Edward Oldfield, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00873015
- Sponsor's protocol ID
- 14024
- Other IDs
- 1R44NS063485-01
- Status last verified
- May 2020
- First submitted
- 31 Mar 2009
- Last updated
- 21 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23706046
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Pharmacokinetic Evaluation of Sodium Nitrite Injection for the Prevention of Post-Subarachnoid Hemorrhage Induced Vasospasm
- ClinicalTrials.gov ID
- NCT00873015
- Acronym / sponsor ID
- 14024
- Conditions
- Subarachnoid Hemorrhage
- Keywords
- Cerebral aneurysm, Subarachnoid hemorrhage, Nitrite
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Hope PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Apr 2010
- Primary completion
- Nov 2010 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 1 Apr 2009 (estimated)
- Results
- Posted 16 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrite | Experimental | Drug: Sodium nitriteContinuous intravenous infusion of Sodium Nitrite |
| Vehicle control | Placebo comparator | Drug: SalineContinuous intravenous infusion of saline |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Ruptured cerebral aneurysm
Key exclusion criteria (1 listed)
- Pregnancy, sickle cell disease, G6PD deficiency, anticoagulant therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium nitriteAlso: Sodium Nitrite Injection NDC 60267-311-1014 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 | Drug | Nitrite |
| SalineAlso: Sterile saline14 day continuous infusion of a vehicle control infusion | Drug | Vehicle control |
Primary outcome
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.
2 secondary outcomes
Safety of a 14 Day Infusion of Sodium Nitrite
Time frame: 14 days
Efficacy of 14 Day Infusion of Sodium Nitrite
Time frame: 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23706046Oldfield 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward Oldfield, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium nitrite and Saline in people with Subarachnoid Hemorrhage, run by Hope Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Plasma Nitrite Concentration (Micromol/L) (time frame: multiple time points up to the end of day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00873015, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2020.