StrokePhase 2NCT03276494
Safety & Tolerability of Hypertonic Saline Administration Via Intraosseous Access
A Phase 2 study testing Intraosseous and Hypertonic saline in people with Stroke and Intracranial Hypotension, run by Ohio State University at 1 site in United States.
Trial summary
Hypertonic saline is used to treat elevated intracranial pressure. Intraosseous vascular access has been used to administer fluids and medications. This study combines these to administer 3% hypertonic saline via IO. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Intracranial Hypotension, Cerebral Edema
- What is being tested?
- Intraosseous and Hypertonic saline
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2017to 21 Apr 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- NCCU patients in which osmotherapy with HTS is planned (standard of care
- Does not already have a CVC or PICC.
Who cannot join
- <18 years old
- Known pregnancy
- Long bone fracture in the targeted site
- Proximity to prosthetic joint
- Excessive tissue/absence of anatomical landmarks
- History of osteopetrosis
Show all 11Show fewer
- Previous significant orthopedic procedure at site
- Prosthetic limb or joint
- IO catheter use in the past 48 hours of the target bone
- Infection at the area of insertion
- Hypersensitivity to lidocaine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intraosseous Administration of Hypertonic Saline in Acute Brain-injured Patients: A Prospective Case Series and Literature Review
Hypertonic saline is used to treat elevated intracranial pressure. Intraosseous vascular access has been used to administer fluids and medications. This study combines these to administer 3% hypertonic saline via IO.
Read the detailed description
HTS is used to mitigate and temporize intracranial pressure (ICP) elevations and cerebral edema by creating an osmotic gradient across the cell wall. HTS is part of the elevated ICP algorithm in the emergency neurologic life support protocols HTS is superior to mannitol which is the alternate osmotherapy agent . HTS is typically administered via central vascular access due to the concern that if extravasation of the infusion occurs, tissue damage from cell implosion can occur
The IO route is generally accepted in resuscitation environments including the emergency department, EMS, and military settings with some authors recommending the IO as a primary method of obtaining emergency vascular access The adult advanced cardiac life support (ACLS) guidelines recommend either intravenous or IO access.
A number of studies have established the safety of IO administration of hypertonic solutions. Randomized adult pigs to IO 7.5% HTS, IO 3% HTS, and 0.9% isotonic saline and found regular tissue morphology, no necrosis or microscopic ischemic changes in the HTS groups. Several studies conducted to evaluate the efficacy of hypertonic solutions on resuscitation for hemorrhagic shock used the IO route and did not make note of problems arising from the administration of IO HTS. Another study using a canine model of hemorrhagic shock briefly mentioned transient lameness in the IO HTS group, but this resolved by 48 hours . While the majority of studies using hypertonic saline solutions did not make note of complications, one study induced hemorrhagic shock in dehydrated swine and resuscitated one group with 7.5% HTS and noted a high rate of local complications from soft tissue and bone marrow necrosis .
One study noted a subgroup of patients in which IO access was obtained on conscious patients. None of the patients received local anesthetic and none reported pain during insertion. Eighteen of the 22 conscious patients reported pain during fluid administration. Central venous catheter (CVC) placement is the current standard of care; even with local anesthesia it can be painful. Most of the potential subjects, due to the nature of their severe neurologic injury, may not be affected by the pain associated with IO fluid administration. Manufacturer literature suggests the use of lidocaine to anesthetize the bone before infusing if possible (Teleflex).
It is expected that utilizing IO for vascular access in the ICU will be safe and tolerable. If this study confirms the anticipated results, there are numerous implications. First, neurologically injured patients requiring emergent HTS may have faster access to this therapy. A study comparing IO to CVC access undergoing resuscitation in the emergency department found IO to be faster to insert (2.3 vs. 9.9 minutes) and had fewer failures to access on the first attempt. Second, serious complications from IO were absent compared with severe to life-threatening mechanical complications from CVC including pneumothorax, damage to the carotid artery, and bleeding which were cited at 0.7%-2.1% depending on site. And thirdly, central line associated blood stream infections (CLABSI) are a leading cause of hospital acquired infections in the ICU and are associated with higher mortality. CLABSI rates are measured by number of infections per 1,000 catheter days and shorter CVC dwell time is prudent. If a reliable and rapid source of vascular access could postpone or eliminate CVC insertion, risk of CLABSI may be reduced. These potential benefits outweigh the minimal expected risk.
- Conditions
- Stroke, Intracranial Hypotension, Cerebral Edema
- Being tested
- Intraosseous, Hypertonic saline
- Medical subject headings
- Stroke, Intracranial Hypotension, Brain Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IntraosseousDevice
Intraosseous administration of hypertonic saline
Hypertonic salineDrug
Intraosseous administration of hypertonic saline
| Study group | Role | What they receive |
|---|---|---|
| Intraosseous | Other | Administration of intraosseous hypertonic saline Receives: Device: Intraosseous; Drug: Hypertonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Tissue Damage
Number of subjects with tissue damage (e.g. Myonecrosis, Skin necrosis, Extravasation, Compartment syndrome, Osteomyelitis). These data points will be determined by clinician assessment.
Measured: 24 hours
Secondary outcomes (1)
Pain Scale
Pain (CPOT-critical care pain observation tool). All non-verbal subjects have pain assessed with a CPOT score, as observed by clinicians. The CPOT is a validated pain score for nonverbal patients. This tool assesses pain with nonverbal indicators, adding 1-2 points for several nonverbal indicators of pain, 0 if the nonverbal indicator is absent, and is reported as a total summed score. It ranges from 0-8, with 0 indicating no pain and 8 indicating high pain.
No patients were verbal, so the numeric pain rating scale was not used for any patients.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start21 Apr 2017
- Primary completion21 Apr 2018
- Study completion21 Apr 2018
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.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- prospective case series
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Archana Hinduja, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276494
- Sponsor's protocol ID
- 2017H0067
- Status last verified
- Jun 2019
- First submitted
- 29 Jun 2017
- Last updated
- 9 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: manuscript on the case series has been submitted
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraosseous Administration of Hypertonic Saline in Acute Brain-injured Patients: A Prospective Case Series and Literature Review
- ClinicalTrials.gov ID
- NCT03276494
- Acronym / sponsor ID
- 2017H0067
- Conditions
- Stroke, Intracranial Hypotension, Cerebral Edema
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 21 Apr 2017 (actual)
- Primary completion
- 21 Apr 2018 (actual)
- Study completion
- 21 Apr 2018 (actual)
- First posted
- 8 Sep 2017 (actual)
- Results
- Posted 9 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypertonic saline is used to treat elevated intracranial pressure. Intraosseous vascular access has been used to administer fluids and medications. This study combines these to administer 3% hypertonic saline via IO.
Detailed description
HTS is used to mitigate and temporize intracranial pressure (ICP) elevations and cerebral edema by creating an osmotic gradient across the cell wall. HTS is part of the elevated ICP algorithm in the emergency neurologic life support protocols HTS is superior to mannitol which is the alternate osmotherapy agent . HTS is typically administered via central vascular access due to the concern that if extravasation of the infusion occurs, tissue damage from cell implosion can occur
The IO route is generally accepted in resuscitation environments including the emergency department, EMS, and military settings with some authors recommending the IO as a primary method of obtaining emergency vascular access The adult advanced cardiac life support (ACLS) guidelines recommend either intravenous or IO access.
A number of studies have established the safety of IO administration of hypertonic solutions. Randomized adult pigs to IO 7.5% HTS, IO 3% HTS, and 0.9% isotonic saline and found regular tissue morphology, no necrosis or microscopic ischemic changes in the HTS groups. Several studies conducted to evaluate the efficacy of hypertonic solutions on resuscitation for hemorrhagic shock used the IO route and did not make note of problems arising from the administration of IO HTS. Another study using a canine model of hemorrhagic shock briefly mentioned transient lameness in the IO HTS group, but this resolved by 48 hours . While the majority of studies using hypertonic saline solutions did not make note of complications, one study induced hemorrhagic shock in dehydrated swine and resuscitated one group with 7.5% HTS and noted a high rate of local complications from soft tissue and bone marrow necrosis .
One study noted a subgroup of patients in which IO access was obtained on conscious patients. None of the patients received local anesthetic and none reported pain during insertion. Eighteen of the 22 conscious patients reported pain during fluid administration. Central venous catheter (CVC) placement is the current standard of care; even with local anesthesia it can be painful. Most of the potential subjects, due to the nature of their severe neurologic injury, may not be affected by the pain associated with IO fluid administration. Manufacturer literature suggests the use of lidocaine to anesthetize the bone before infusing if possible (Teleflex).
It is expected that utilizing IO for vascular access in the ICU will be safe and tolerable. If this study confirms the anticipated results, there are numerous implications. First, neurologically injured patients requiring emergent HTS may have faster access to this therapy. A study comparing IO to CVC access undergoing resuscitation in the emergency department found IO to be faster to insert (2.3 vs. 9.9 minutes) and had fewer failures to access on the first attempt. Second, serious complications from IO were absent compared with severe to life-threatening mechanical complications from CVC including pneumothorax, damage to the carotid artery, and bleeding which were cited at 0.7%-2.1% depending on site. And thirdly, central line associated blood stream infections (CLABSI) are a leading cause of hospital acquired infections in the ICU and are associated with higher mortality. CLABSI rates are measured by number of infections per 1,000 catheter days and shorter CVC dwell time is prudent. If a reliable and rapid source of vascular access could postpone or eliminate CVC insertion, risk of CLABSI may be reduced. These potential benefits outweigh the minimal expected risk.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- prospective case series
| Arm | Type | Receives |
|---|---|---|
| Intraosseous | Other | Device: Intraosseous, Drug: Hypertonic salineAdministration of intraosseous hypertonic saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- NCCU patients in which osmotherapy with HTS is planned (standard of care
- Does not already have a CVC or PICC.
Key exclusion criteria (11 listed)
- <18 years old
- Known pregnancy
- Long bone fracture in the targeted site
- Proximity to prosthetic joint
- Excessive tissue/absence of anatomical landmarks
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 |
|---|---|---|
| IntraosseousIntraosseous administration of hypertonic saline | Device | Intraosseous |
| Hypertonic salineIntraosseous administration of hypertonic saline | Drug | Intraosseous |
Primary outcome
Number of Subjects With Tissue Damage
Time frame: 24 hours
Number of subjects with tissue damage (e.g. Myonecrosis, Skin necrosis, Extravasation, Compartment syndrome, Osteomyelitis). These data points will be determined by clinician assessment.
1 secondary outcome
Pain Scale
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. manuscript on the case series has been submitted
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Intraosseous and Hypertonic saline in people with Stroke and Intracranial Hypotension, run by Ohio State University 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 2 inclusion and 11 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 9 Jul 2019. 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. 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 9 Jul 2019). 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?
Number of Subjects With Tissue Damage (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2019.