Traumatic Brain InjuryAVPNCT00795366
Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
A study testing arginine vasopressin and Standard catecholamine in people with Traumatic Brain Injury, run by University of Miami at 1 site in United States.
Trial summary
Traumatic brain injury (TBI) is among the leading causes of trauma death and disability in both civilian and military populations. The damage that occurs at the instant of trauma cannot be modified; the secondary injuries that occur afterward are the impediments to recovery and can be influenced by the physician. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- arginine vasopressin and Standard catecholamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Sep 2014
- Phase
- Interventional
- 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
- Age >/= 18 yrs,
- Primary admission to the hospital within 8 h after injury
- Closed head injury
- Potential for intracranial pressure monitoring
Who cannot join
- Pregnant or nursing women
- Hemodynamic instability after initial resuscitation
- Vasopressor therapy for greater than 6 hours
Trial locations and contacts
1 site in 1 country.
About this study
Traumatic brain injury (TBI) is among the leading causes of trauma death and disability in both civilian and military populations. The damage that occurs at the instant of trauma cannot be modified; the secondary injuries that occur afterward are the impediments to recovery and can be influenced by the physician. Cerebral ischemia is the most important secondary event that determines outcome following TBI. To minimize ischemic episodes once the patient has arrived at the hospital, most treatments are aimed at optimizing cerebral perfusion pressure (CPP). The cornerstones of these treatments include mannitol, to reduce intracranial pressure (ICP), and catecholamines, such as phenylephrine (PE), to increase mean arterial pressure (MAP), but these agents have undesired side effects. Nevertheless, once they lose potency, there are few alternatives. The main objective of this proposal to develop a new therapeutic option for CPP management in TBI patients using arginine vasopressin (AVP).
AVP is the endogenous anti-diuretic hormone. It is FDA-approved for use in the diagnosis and treatment of diabetes insipidus, for the prevention and treatment of post-operative abdominal distention, and in abdominal radiography to dispel interfering gas shadows. It has been used off-label for several other conditions. There is minimal information on its therapeutic potential after TBI. The investigators have demonstrated that AVP during fluid resuscitation rapidly restored hemodynamics, CPP, and improves acute survival in a clinically-relevant model of TBI. The investigators observed similar short term benefits after chest and liver trauma. Nevertheless, AVP has actions that could mask any short term benefit. The investigators have already defined risks and benefits of AVP therapy, relative to PE, in four different clinically-relevant laboratory model. The investigators now plan to evaluate this new therapy relative to the current evidence-based guideline for CPP management in TBI patients.
Read more
The working hypothesis is that the risk/benefit profile for AVP is equal, or superior to, PE at equi-effective doses for the management of CPP following TBI. A corollary is that a higher CPP can be safely tolerated with AVP vs catecholamines.
THE INVESTIGATORS AIM TO: Determine whether AVP is safe and effective to maintain CPP = 60 mm Hg in TBI patients.
Read the detailed description
This is a randomized, controlled, open-label clinical trial comparing vasopressin and catecholamines for cerebral perfusion pressure (CPP) control after a traumatic brain injury (TBI).
Once a neurosurgeon is consulted for a patient presenting with a TBI, they will review entry criteria and refer to study personnel to obtain informed consent.
After informed consent, subjects will be randomized into one of the 2 groups to receive either a catecholamine at the discretion of the attending physicians or vasopressin (AVP). A 6 hour dose of non-study drug will be permitted prior to initiation of study drug. The amount of study drug will be titrated to maintain cerebral perfusion pressure within normal limits. Subjects will be followed until they can maintain their CPP without vasopressor medication. Data collection will include amount and duration of vasopressor therapy and resulting cerebral perfusion pressure and time until successful weaning from vasopressor therapy.
All subsequent clinical care will be at the discretion of the attending physician.
The standard protocol/procedure for the discontinuation of drugs in each arm of the study is as follows: Vasopressors are discontinued in a step-wise fashion, regardless of the specific agent or the specific ICU patient population. In patients with severe traumatic brain injury (TBI), cerebral perfusion pressure (CPP) is maintained between 60 and 70 mmHg with vasopressors. When intracranial pressure (ICP) begins to correct (decrease), vasopressors are titrated downward slowly to maintain CPP. This continues until ICP is normalized and systemic hemodynamics are able to support a normal CPP. At this point, vasopressors are withdrawn completely. This process is standard regardless of the choice of vasopressor.
- Conditions
- Traumatic Brain Injury
- Being tested
- arginine vasopressin, Standard catecholamine
- Keywords
- TBI, trauma, brain
- Medical subject headings
- Brain Injuries, Traumatic, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arginine vasopressinDrug
Titrated to cerebral perfusion pressure greater than 60 mm Hg
Standard catecholamineDrug
Titrated catecholamine of attending physicians preference to cerebral perfusion pressure greater than 60 mm Hg.
| Study group | Role | What they receive |
|---|---|---|
| AVP, arginine vasopressin | Active comparator | Vasopressin Receives: Drug: arginine vasopressin |
| Standard Catecholamine | Active comparator | levophed, dopamine, phenylephrine) Receives: Drug: Standard catecholamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time ICP >20
The number of hours that participants remained with intracranial pressure above 20 mmHg
Measured: The number of hours during the first 5 days of intracranial pressure monitoring
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2008 (estimated)
- Study startSep 2008
- Primary completionSep 2014
- Study completionSep 2014
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 (4)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kenneth Proctor, University of Miami
- Investigators
- Kenneth G Proctor, PhD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00795366
- Sponsor's protocol ID
- 20060949
- Acronym
- AVP
- Status last verified
- Dec 2014
- First submitted
- 20 Nov 2008
- Last updated
- 12 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Dudkiewicz M, Proctor KG. Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin. Crit Care Med. 2008 Sep;36(9):2641-50. doi: 10.1097/CCM.0b013e3181847af3.
PubMed 18679110Sanui M, King DR, Feinstein AJ, Varon AJ, Cohn SM, Proctor KG. Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury. Crit Care Med. 2006 Feb;34(2):433-8. doi: 10.1097/01.ccm.0000196206.83534.39.
PubMed 16424725Feinstein AJ, Cohn SM, King DR, Sanui M, Proctor KG. Early vasopressin improves short-term survival after pulmonary contusion. J Trauma. 2005 Oct;59(4):876-82; discussion 882-3. doi: 10.1097/01.ta.0000187654.24146.22.
PubMed 16374276Feinstein AJ, Patel MB, Sanui M, Cohn SM, Majetschak M, Proctor KG. Resuscitation with pressors after traumatic brain injury. J Am Coll Surg. 2005 Oct;201(4):536-45. doi: 10.1016/j.jamcollsurg.2005.05.031.
PubMed 16183491
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
- ClinicalTrials.gov ID
- NCT00795366
- Acronym / sponsor ID
- AVP / 20060949
- Conditions
- Traumatic Brain Injury
- Keywords
- TBI, trauma, brain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 21 Nov 2008 (estimated)
- Results
- Posted 12 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Traumatic brain injury (TBI) is among the leading causes of trauma death and disability in both civilian and military populations. The damage that occurs at the instant of trauma cannot be modified; the secondary injuries that occur afterward are the impediments to recovery and can be influenced by the physician. Cerebral ischemia is the most important secondary event that determines outcome following TBI. To minimize ischemic episodes once the patient has arrived at the hospital, most treatments are aimed at optimizing cerebral perfusion pressure (CPP). The cornerstones of these treatments include mannitol, to reduce intracranial pressure (ICP), and catecholamines, such as phenylephrine (PE), to increase mean arterial pressure (MAP), but these agents have undesired side effects. Nevertheless, once they lose potency, there are few alternatives. The main objective of this proposal to develop a new therapeutic option for CPP management in TBI patients using arginine vasopressin (AVP).
AVP is the endogenous anti-diuretic hormone. It is FDA-approved for use in the diagnosis and treatment of diabetes insipidus, for the prevention and treatment of post-operative abdominal distention, and in abdominal radiography to dispel interfering gas shadows. It has been used off-label for several other conditions. There is minimal information on its therapeutic potential after TBI. The investigators have demonstrated that AVP during fluid resuscitation rapidly restored hemodynamics, CPP, and improves acute survival in a clinically-relevant model of TBI. The investigators observed similar short term benefits after chest and liver trauma. Nevertheless, AVP has actions that could mask any short term benefit. The investigators have already defined risks and benefits of AVP therapy, relative to PE, in four different clinically-relevant laboratory model. The investigators now plan to evaluate this new therapy relative to the current evidence-based guideline for CPP management in TBI patients.
The working hypothesis is that the risk/benefit profile for AVP is equal, or superior to, PE at equi-effective doses for the management of CPP following TBI. A corollary is that a higher CPP can be safely tolerated with AVP vs catecholamines.
THE INVESTIGATORS AIM TO: Determine whether AVP is safe and effective to maintain CPP = 60 mm Hg in TBI patients.
Detailed description
This is a randomized, controlled, open-label clinical trial comparing vasopressin and catecholamines for cerebral perfusion pressure (CPP) control after a traumatic brain injury (TBI).
Once a neurosurgeon is consulted for a patient presenting with a TBI, they will review entry criteria and refer to study personnel to obtain informed consent.
After informed consent, subjects will be randomized into one of the 2 groups to receive either a catecholamine at the discretion of the attending physicians or vasopressin (AVP). A 6 hour dose of non-study drug will be permitted prior to initiation of study drug. The amount of study drug will be titrated to maintain cerebral perfusion pressure within normal limits. Subjects will be followed until they can maintain their CPP without vasopressor medication. Data collection will include amount and duration of vasopressor therapy and resulting cerebral perfusion pressure and time until successful weaning from vasopressor therapy.
All subsequent clinical care will be at the discretion of the attending physician.
The standard protocol/procedure for the discontinuation of drugs in each arm of the study is as follows: Vasopressors are discontinued in a step-wise fashion, regardless of the specific agent or the specific ICU patient population. In patients with severe traumatic brain injury (TBI), cerebral perfusion pressure (CPP) is maintained between 60 and 70 mmHg with vasopressors. When intracranial pressure (ICP) begins to correct (decrease), vasopressors are titrated downward slowly to maintain CPP. This continues until ICP is normalized and systemic hemodynamics are able to support a normal CPP. At this point, vasopressors are withdrawn completely. This process is standard regardless of the choice of vasopressor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AVP, arginine vasopressin | Active comparator | Drug: arginine vasopressinVasopressin |
| Standard Catecholamine | Active comparator | Drug: Standard catecholaminelevophed, dopamine, phenylephrine) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age >/= 18 yrs,
- Primary admission to the hospital within 8 h after injury
- Closed head injury
- Potential for intracranial pressure monitoring
Key exclusion criteria (3 listed)
- Pregnant or nursing women
- Hemodynamic instability after initial resuscitation
- Vasopressor therapy for greater than 6 hours
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 |
|---|---|---|
| arginine vasopressinTitrated to cerebral perfusion pressure greater than 60 mm Hg | Drug | AVP, arginine vasopressin |
| Standard catecholamineTitrated catecholamine of attending physicians preference to cerebral perfusion pressure greater than 60 mm Hg. | Drug | Standard Catecholamine |
Primary outcome
Time ICP >20
Time frame: The number of hours during the first 5 days of intracranial pressure monitoring
The number of hours that participants remained with intracranial pressure above 20 mmHg
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18679110Dudkiewicz M, Proctor KG. Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin. Crit Care Med. 2008 Sep;36(9):2641-50. doi: 10.1097/CCM.0b013e3181847af3.
- Background: PubMed 16424725Sanui M, King DR, Feinstein AJ, Varon AJ, Cohn SM, Proctor KG. Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury. Crit Care Med. 2006 Feb;34(2):433-8. doi: 10.1097/01.ccm.0000196206.83534.39.
- Background: PubMed 16374276Feinstein AJ, Cohn SM, King DR, Sanui M, Proctor KG. Early vasopressin improves short-term survival after pulmonary contusion. J Trauma. 2005 Oct;59(4):876-82; discussion 882-3. doi: 10.1097/01.ta.0000187654.24146.22.
- Background: PubMed 16183491Feinstein AJ, Patel MB, Sanui M, Cohn SM, Majetschak M, Proctor KG. Resuscitation with pressors after traumatic brain injury. J Am Coll Surg. 2005 Oct;201(4):536-45. doi: 10.1016/j.jamcollsurg.2005.05.031.
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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.
Kenneth G Proctor, PhD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing arginine vasopressin and Standard catecholamine in people with Traumatic Brain Injury, run by University of Miami 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 4 inclusion and 3 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 12 Dec 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2014). 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?
Time ICP >20 (time frame: The number of hours during the first 5 days of intracranial pressure monitoring). 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 NCT00795366, which also lists 4 linked publications.
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 12 Dec 2014.