FeverINTREPIDNCT02996266
Impact of Fever Prevention in Brain Injured Patients
A study testing Targeted Temperature Management in people with Fever and Ischemic Stroke, run by C. R. Bard at 40 sites in 6 countries.
Trial summary
This study will assess the impact of fever prevention on fever burden and short- and long-term neurologic outcomes in brain injured patients. Half of the subjects will undergo fever prevention using a targeted temperature management system and half of the subjects will be treated for fever should it develop. Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Fever, Ischemic Stroke, Intracerebral Hemorrhage
- What is being tested?
- Targeted Temperature Management
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 686 participants
- Where
- 40 sitesin 6 countries
- Study dates
- Jan 2017to 12 May 2022
- 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 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted with a primary neurological diagnosis of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage
- Prior to onset of acute symptoms, was considered functionally independent (mRS 0-2)
- Meets disease-specific criteria
Who cannot join
- Fever (≥38°C) prior to study enrollment
- Pre-existing neurological, psychiatric, or other condition that would confound neurological assessment or would make it difficult to accurately assess neurologic and/or functional outcome
- Has a pre-morbid condition with poor likelihood of survival to 6 months
- Has a pre-morbid mRS ≥3
- Diagnosed with brain death
- Is undergoing therapeutic hypothermia therapy
Show all 10Show fewer
- Has sustained neurological injury felt to be catastrophic with little chance of recovery
- Has a skin condition in which the use of the ArcticGel Pads is contraindicated (i.e., skin that has signs of ulceration, burns, hives, or rash)
- Has poor skin integrity or poor tissue perfusion
- Participation in a concurrent investigational / interventional study (medical device or drug)
Trial locations and contacts
40 sites in 6 countries.
40 sites in 6 countries
United States28 sites
The University of New Mexico Health Science Center
Albuquerque, New Mexico, 87131
University of Colorado Hospital
Aurora, Colorado, 80045
University of Maryland Medical Center
Baltimore, Maryland, 21201
Boston University Medical Center
Boston, Massachusetts, 02118
Erlanger Health System Baroness Hospital
Chattanooga, Tennessee, 37403
Rush University
Chicago, Illinois, 60612
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Riverside Methodist Hospital
Columbus, Ohio, 43214
Henry Ford Hospital
Detroit, Michigan, 48202
Duke University Medical Center
Durham, North Carolina, 27710
Swedish Medical Center
Englewood, Colorado, 80113
University of Florida
Gainesville, Florida, 32610
Spectrum Health Hospitals
Grand Rapids, Michigan, 49506
Hershey Medical Center
Hershey, Pennsylvania, 17033
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Southern California
Los Angeles, California, 90033
Norton Neuroscience Institute
Louisville, Kentucky, 40241
Yale New Haven Hospital
New Haven, Connecticut, 06520
Tulane Medical Center
New Orleans, Louisiana, 70112
Mount Sinai Hospital
New York, New York, 10029
Columbia University, New York - Presbyterian Hospital
New York, New York, 10032
Stanford University Hospital
Palo Alto, California, 94304
Providence St Vincent Medical Center
Portland, Oregon, 97225
Rhode Island Hospital
Providence, Rhode Island, 02903
Harborview Medical Center
Seattle, Washington, 98104
Washington University
St Louis, Missouri, 63110
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
University of Massachusetts Worcester
Worcester, Massachusetts, 01655
Germany4 sites
Charité - Universitätsmedizin Berlin
Berlin, D-10117
Technische Universitat Dresden
Dresden, 01062
Universitätsklinikum Jena
Jena, 07747
LMU München, Klinikum Großhadern
Munich, 81377
South Korea4 sites
Keimyung University Dongsan Hospital
Daegu
Asan Medical Center
Seoul
Seoul National University Bundang Hospital
Seoul
Seoul National University Hospital
Seoul
Australia2 sites
Royal Adelaide Hospital
Adelaide, South Australia
Royal North Shore Hospital
Sydney, New South Wales, 2065
About this study
This study will assess the impact of fever prevention on fever burden and short- and long-term neurologic outcomes in brain injured patients. Half of the subjects will undergo fever prevention using a targeted temperature management system and half of the subjects will be treated for fever should it develop.
Read the detailed description
Multiple studies demonstrate that fever / elevated temperature is associated with poor outcomes in brain injured patients; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. This study will be conducted to assess the impact of advanced temperature control to prevent fever in brain injured patients. The fever prevention group will use the Arctic Sun Temperature Management System and will be compared to standard care patients in whom fever may spontaneously develop. If fever develops in a patient in the standard care group, they will be treated with standard fever care measures according to a step-wise algorithm, consisting primarily of intermittent antipyretics (e.g., acetaminophen) and cooling blankets and, when necessary, advanced targeted temperature management devices.
- Being tested
- Targeted Temperature Management, Standard Care
- Keywords
- Targeted Temperature Management
- Medical subject headings
- Fever, Ischemic Stroke, Cerebral Hemorrhage, Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted Temperature ManagementDevice
Also called Arctic Sun 5000 Temperature Management System
Prophylactic normothermia
Standard CareOther
No intervention to control temperature unless fever occurs
| Study group | Role | What they receive |
|---|---|---|
| Fever Prevention | Experimental | Fever will be prevented using a surface targeted temperature management system Receives: Device: Targeted Temperature Management |
| Standard Care | Active comparator | Standard care in which fever may spontaneously develop Receives: Other: Standard Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fever Burden
Daily average fever burden (°C-hour)
Measured: Up to 14 days
Secondary outcomes (15)
Primary Neurologic Outcome: Modified Rankin Scale Short-Term
Modified Rankin Scale is a 6-category outcome measurement with 0 = no limitations, no symptoms and 6 = death.
Measured: 3-months post injury
Other Neurologic Outcomes: NIH Stroke Scale Short-Term
NIH Stroke Scale is a systematic, quantitative assessment tool to measure stroke-related neurological deficit. Scores range from 0 to 42, with higher scores indicating worse outcome.
Measured: 3-months post injury
Other Neurologic Outcomes: Barthel Index Short-Term
Barthel Index is an assessment of functional independence. Scores range from 0 to 100, with lower scores indicating worse outcome.
Measured: 3-months post injury
Other Neurologic Outcomes: Glasgow Outcome Scale Extended Short-Term
Glasgow Outcome Scale assesses functional outcome after acute brain injury. Scores range from 1-8, with lower scores indicating worse outcome.
Measured: 3-months post injury
Other Neurologic Outcomes: Montreal Cognitive Assessment Short-Term
Montreal Cognitive Assessment assesses for cognitive impairment. Scores range from 0-30, with lower scores indicating worse outcome.
Measured: 3-months post injury
Primary Neurologic Outcome: Modified Rankin Scale Mid-Term
Modified Rankin Scale is a 6-category outcome measurement with 0 = no limitations, no symptoms and 6 = death.
Measured: 6-months post injury
Other Neurologic Outcomes: NIH Stroke Scale Mid-Term
NIH Stroke Scale is a systematic, quantitative assessment tool to measure stroke-related neurological deficit. Scores range from 0 to 42, with higher scores indicating worse outcome.
Measured: 6-months post injury
Other Neurologic Outcomes: Barthel Index Mid-Term
Barthel Index is an assessment of functional independence. Scores range from 0 to 100, with lower scores indicating worse outcome.
Measured: 6-months post injury
Other Neurologic Outcomes: Glasgow Outcome Scale Extended Mid-Term
Glasgow Outcome Scale assesses functional outcome after acute brain injury. Scores range from 1-8, with lower scores indicating worse outcome.
Measured: 6-months post injury
Other Neurologic Outcomes: Montreal Cognitive Assessment Mid-Term
Montreal Cognitive Assessment assesses for cognitive impairment. Scores range from 0-30, with lower scores indicating worse outcome.
Measured: 6-months post injury
Primary Neurologic Outcome: Modified Rankin Scale Long-Term
Modified Rankin Scale is a 6-category outcome measurement with 0 = no limitations, no symptoms and 6 = death.
Measured: 12-months post injury
Adverse Events
An untoward medical occurrence, unintended disease or injury, or unanticipated complication
Measured: From date of randomization until hospital discharge, assessed up to 30 days
Major Adverse Events
MAEs defined as one of the following: pneumonia, sepsis, malignant cerebral edema, death
Measured: From date of randomization until end of study, assessed up to 12 months
Number of Participants With Infection
Healthcare associated infection
Measured: From date of randomization until hospital discharge, assessed up to 30 days
Number of Subjects With Shivering
Shivering greater than or equal to 1 on the Bedside Shivering Assessment Scale (BSAS). BSAS scores range from 0-3 with 0 indicating no shivering noted and 3 indicating severe shivering involving gross movements of the trunk and upper and lower extremities.
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2016 (estimated)
- Study startJan 2017
- Primary completion12 May 2022
- Study completion12 May 2022
Why it stopped: Futility
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 (3)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by C. R. BardThe 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 686 participants (actual)
Sponsor and investigators
- Lead sponsor
- C. R. Bard
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Yale University, Boston University
- Responsible party
- Sponsor
- Investigators
- David M. Greer, MD, MA, Principal investigator, Boston UniversityKevin N. Sheth, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02996266
- Sponsor's protocol ID
- BMD-1111
- Acronym
- INTREPID
- Status last verified
- Aug 2023
- First submitted
- 5 Dec 2016
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Greer DM, Helbok R, Badjatia N, Ko SB, Guanci MM, Sheth KN; INTREPID Study Group. Fever Prevention in Patients With Acute Vascular Brain Injury: The INTREPID Randomized Clinical Trial. JAMA. 2024 Nov 12;332(18):1525-1534. doi: 10.1001/jama.2024.14745.
PubMed 39320879Greer DM, Ritter J, Helbok R, Badjatia N, Ko SB, Guanci M, Sheth KN. Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial. Neurocrit Care. 2021 Oct;35(2):577-589. doi: 10.1007/s12028-021-01208-1. Epub 2021 Mar 24.
PubMed 33761119Cronberg T, Greer DM, Lilja G, Moulaert V, Swindell P, Rossetti AO. Brain injury after cardiac arrest: from prognostication of comatose patients to rehabilitation. Lancet Neurol. 2020 Jul;19(7):611-622. doi: 10.1016/S1474-4422(20)30117-4.
PubMed 32562686
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Fever Prevention in Brain Injured Patients
- ClinicalTrials.gov ID
- NCT02996266
- Acronym / sponsor ID
- INTREPID / BMD-1111
- Keywords
- Targeted Temperature Management
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 686 participants (actual)
- Lead sponsor
- C. R. BardIndustry (pharma, biotech, devices)
- Collaborators
- Yale University, Boston University
- Study start
- Jan 2017 (actual)
- Primary completion
- 12 May 2022 (actual)
- Study completion
- 12 May 2022 (actual)
- First posted
- 19 Dec 2016 (estimated)
- Results
- Posted 21 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the impact of fever prevention on fever burden and short- and long-term neurologic outcomes in brain injured patients. Half of the subjects will undergo fever prevention using a targeted temperature management system and half of the subjects will be treated for fever should it develop.
Detailed description
Multiple studies demonstrate that fever / elevated temperature is associated with poor outcomes in brain injured patients; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. This study will be conducted to assess the impact of advanced temperature control to prevent fever in brain injured patients. The fever prevention group will use the Arctic Sun Temperature Management System and will be compared to standard care patients in whom fever may spontaneously develop. If fever develops in a patient in the standard care group, they will be treated with standard fever care measures according to a step-wise algorithm, consisting primarily of intermittent antipyretics (e.g., acetaminophen) and cooling blankets and, when necessary, advanced targeted temperature management devices.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fever Prevention | Experimental | Device: Targeted Temperature ManagementFever will be prevented using a surface targeted temperature management system |
| Standard Care | Active comparator | Other: Standard CareStandard care in which fever may spontaneously develop |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Admitted with a primary neurological diagnosis of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage
- Prior to onset of acute symptoms, was considered functionally independent (mRS 0-2)
- Meets disease-specific criteria
Key exclusion criteria (10 listed)
- Fever (≥38°C) prior to study enrollment
- Pre-existing neurological, psychiatric, or other condition that would confound neurological assessment or would make it difficult to accurately assess neurologic and/or functional outcome
- Has a pre-morbid condition with poor likelihood of survival to 6 months
- Has a pre-morbid mRS ≥3
- Diagnosed with brain death
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 |
|---|---|---|
| Targeted Temperature ManagementAlso: Arctic Sun 5000 Temperature Management SystemProphylactic normothermia | Device | Fever Prevention |
| Standard CareNo intervention to control temperature unless fever occurs | Other | Standard Care |
Primary outcome
Fever Burden
Time frame: Up to 14 days
Daily average fever burden (°C-hour)
15 secondary outcomes
Primary Neurologic Outcome: Modified Rankin Scale Short-Term
Time frame: 3-months post injury
Other Neurologic Outcomes: NIH Stroke Scale Short-Term
Time frame: 3-months post injury
Other Neurologic Outcomes: Barthel Index Short-Term
Time frame: 3-months post injury
Other Neurologic Outcomes: Glasgow Outcome Scale Extended Short-Term
Time frame: 3-months post injury
Other Neurologic Outcomes: Montreal Cognitive Assessment Short-Term
Time frame: 3-months post injury
Primary Neurologic Outcome: Modified Rankin Scale Mid-Term
Time frame: 6-months post injury
Other Neurologic Outcomes: NIH Stroke Scale Mid-Term
Time frame: 6-months post injury
Other Neurologic Outcomes: Barthel Index Mid-Term
Time frame: 6-months post injury
Other Neurologic Outcomes: Glasgow Outcome Scale Extended Mid-Term
Time frame: 6-months post injury
Other Neurologic Outcomes: Montreal Cognitive Assessment Mid-Term
Time frame: 6-months post injury
Primary Neurologic Outcome: Modified Rankin Scale Long-Term
Time frame: 12-months post injury
Adverse Events
Time frame: From date of randomization until hospital discharge, assessed up to 30 days
Major Adverse Events
Time frame: From date of randomization until end of study, assessed up to 12 months
Number of Participants With Infection
Time frame: From date of randomization until hospital discharge, assessed up to 30 days
Number of Subjects With Shivering
Time frame: Up to 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39320879Greer DM, Helbok R, Badjatia N, Ko SB, Guanci MM, Sheth KN; INTREPID Study Group. Fever Prevention in Patients With Acute Vascular Brain Injury: The INTREPID Randomized Clinical Trial. JAMA. 2024 Nov 12;332(18):1525-1534. doi: 10.1001/jama.2024.14745.
- Derived from this study: PubMed 33761119Greer DM, Ritter J, Helbok R, Badjatia N, Ko SB, Guanci M, Sheth KN. Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial. Neurocrit Care. 2021 Oct;35(2):577-589. doi: 10.1007/s12028-021-01208-1. Epub 2021 Mar 24.
- Derived from this study: PubMed 32562686Cronberg T, Greer DM, Lilja G, Moulaert V, Swindell P, Rossetti AO. Brain injury after cardiac arrest: from prognostication of comatose patients to rehabilitation. Lancet Neurol. 2020 Jul;19(7):611-622. doi: 10.1016/S1474-4422(20)30117-4.
- Individual participant dataSharing planned: No
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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.
David M. Greer, MD, MA principal investigator
Boston University
Kevin N. Sheth, MD principal investigator
Yale University
40 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Temperature Management in people with Fever and Ischemic Stroke, run by C. R. Bard at 40 sites in 6 countries.
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 3 inclusion and 10 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: stopped early, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Germany, South Korea, Australia, Austria and 1 more country. 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 21 Sep 2023). 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?
Fever Burden (time frame: Up to 14 days). 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 NCT02996266, which also lists 3 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 21 Sep 2023.