Clinical trial NCT02996266: Impact of Fever Prevention in Brain Injured Patients
Official title: Impact of Fever Prevention in Brain Injured Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Fever
Ischemic Stroke
Intracerebral Hemorrhage
Subarachnoid Hemorrhage
Keywords: Targeted Temperature Management
Lead sponsor: C. R. Bard
Sponsor class: INDUSTRY
Collaborators: name: Yale University
name: Boston University
First posted: 2016-12-19
Enrollment: 686
Sex: ALL
Minimum age (years): 21
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Admitted with a primary neurological diagnosis of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage
2. Prior to onset of acute symptoms, was considered functionally independent (mRS 0-2)
3. Meets disease-specific criteria

Exclusion Criteria:

1. Fever (≥38°C) prior to study enrollment
2. 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
3. Has a pre-morbid condition with poor likelihood of survival to 6 months
4. Has a pre-morbid mRS ≥3
5. Diagnosed with brain death
6. Is undergoing therapeutic hypothermia therapy
7. Has sustained neurological injury felt to be catastrophic with little chance of recovery
8. 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)
9. Has poor skin integrity or poor tissue perfusion
10. Participation in a concurrent investigational / interventional study (medical device or drug)

Primary outcomes:
measure: Fever Burden
timeFrame: Up to 14 days
Secondary outcomes:
measure: Primary Neurologic Outcome: Modified Rankin Scale Short-Term
timeFrame: 3-months post injury
measure: Other Neurologic Outcomes: NIH Stroke Scale Short-Term
timeFrame: 3-months post injury
measure: Other Neurologic Outcomes: Barthel Index Short-Term
timeFrame: 3-months post injury
measure: Other Neurologic Outcomes: Glasgow Outcome Scale Extended Short-Term
timeFrame: 3-months post injury
measure: Other Neurologic Outcomes: Montreal Cognitive Assessment Short-Term
timeFrame: 3-months post injury
measure: Primary Neurologic Outcome: Modified Rankin Scale Mid-Term
timeFrame: 6-months post injury
measure: Other Neurologic Outcomes: NIH Stroke Scale Mid-Term
timeFrame: 6-months post injury
measure: Other Neurologic Outcomes: Barthel Index Mid-Term
timeFrame: 6-months post injury
measure: Other Neurologic Outcomes: Glasgow Outcome Scale Extended Mid-Term
timeFrame: 6-months post injury
measure: Other Neurologic Outcomes: Montreal Cognitive Assessment Mid-Term
timeFrame: 6-months post injury
measure: Primary Neurologic Outcome: Modified Rankin Scale Long-Term
timeFrame: 12-months post injury
measure: Adverse Events
timeFrame: From date of randomization until hospital discharge, assessed up to 30 days
measure: Major Adverse Events
timeFrame: From date of randomization until end of study, assessed up to 12 months
measure: Number of Participants With Infection
timeFrame: From date of randomization until hospital discharge, assessed up to 30 days
measure: Number of Subjects With Shivering
timeFrame: Up to 14 days
Other outcomes:
measure: Hospital Length of Stay
timeFrame: From date of randomization until hospital discharge, assessed up to 90 days
measure: ICU Length of Stay
timeFrame: From date of randomization until ICU discharge
measure: Mortality
timeFrame: 7-day (or hospital discharge); 3-, 6-, and 12-months
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Palo Alto
country: United States
facility: Stanford University Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Louisville
country: United States
facility: Norton Neuroscience Institute
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Albuquerque
country: United States
facility: The University of New Mexico Health Science Center
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University, New York - Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Portland
country: United States
facility: Providence St Vincent Medical Center
state: Oregon
city: Hershey
country: United States
facility: Hershey Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Chattanooga
country: United States
facility: Erlanger Health System Baroness Hospital
state: Tennessee
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: Technische Universitat Dresden
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Munich
country: Germany
facility: LMU München, Klinikum Großhadern
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Boston University
name: David M. Greer, MD, MA
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Kevin N. Sheth, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Greer 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.
citation: Cronberg 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.