Impact of Fever Prevention in Brain Injured Patients (INTREPID)

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ClinicalTrials.gov Identifier: NCT02996266

Recruitment Status : Terminated (Futility)

First Posted : December 19, 2016

Last Update Posted : June 21, 2022

Sponsor:

Collaborators:

Yale University

Boston University

Information provided by (Responsible Party):

C. R. Bard

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fever Ischemic Stroke Intracerebral Hemorrhage Subarachnoid Hemorrhage	Device: Targeted Temperature Management Other: Standard Care	Not Applicable

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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	686 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Impact of Fever Prevention in Brain Injured Patients
Actual Study Start Date :	January 2017
Actual Primary Completion Date :	May 12, 2022
Actual Study Completion Date :	May 12, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: COL4A1-related brain small-vessel disease

MedlinePlus related topics: Fever

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fever Prevention Fever will be prevented using a surface targeted temperature management system	Device: Targeted Temperature Management Prophylactic normothermia Other Name: Arctic Sun 5000 Temperature Management System
Active Comparator: Standard Care Standard care in which fever may spontaneously develop	Other: Standard Care No intervention to control temperature unless fever occurs

Outcome Measures

Primary Outcome Measures :

Fever Burden [ Time Frame: Up to 14 days ]
Daily average fever burden (°C-hour)

Secondary Outcome Measures :

Primary Neurologic Outcome: Short-Term [ Time Frame: 3-months post injury ]
Modified Rankin Scale
Other Neurologic Outcomes: NIH Stroke Scale Short-Term [ Time Frame: 3-months post injury ]
NIH Stroke Scale
Other Neurologic Outcomes: Barthel Index Short-Term [ Time Frame: 3-months post injury ]
Barthel Index
Other Neurologic Outcomes: Glasgow Outcome Scale Short-Term [ Time Frame: 3-months post injury ]
Glasgow Outcome Scale
Other Neurologic Outcomes: Montreal Cognitive Assessment Short-Term [ Time Frame: 3-months post injury ]
Montreal Cognitive Assessment
Primary Neurologic Outcome: Mid-Term [ Time Frame: 6-months post injury ]
Modified Rankin Scale
Other Neurologic Outcomes: NIH Stroke Scale Mid-Term [ Time Frame: 6-months post injury ]
NIH Stroke Scale
Other Neurologic Outcomes: Barthel Index Mid-Term [ Time Frame: 6-months post injury ]
Barthel Index
Other Neurologic Outcomes: Glasgow Outcome Scale Mid-Term [ Time Frame: 6-months post injury ]
Glasgow Outcome Scale
Other Neurologic Outcomes: Montreal Cognitive Assessment Mid-Term [ Time Frame: 6-months post injury ]
Montreal Cognitive Assessment
Primary Neurologic Outcome: Long-Term [ Time Frame: 12-months post injury ]
Modified Rankin Scale
Adverse Events [ Time Frame: From date of randomization until hospital discharge, assessed up to 30 days ]
An untoward medical occurrence, unintended disease or injury, or unanticipated complication
Infection Rate [ Time Frame: From date of randomization until hospital discharge, assessed up to 30 days ]
Healthcare associated infection
Incidence of Shivering [ Time Frame: Up to 14 days ]
Shivering greater than or equal to 1 on the Bedside Shivering Assessment Scale

Other Outcome Measures:

Length of Stay [ Time Frame: From date of randomization until hospital discharge, assessed up to 90 days ]
ICU and overall hospital length of stay
Mortality [ Time Frame: 7-day (or hospital discharge); 3-, 6-, and 12-months ]
Mortality

Eligibility Criteria

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Ages Eligible for Study:	21 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
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)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02996266

Locations

Show 40 study locations

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United States, California
University of Southern California
Los Angeles, California, United States, 90033
Stanford University Hospital
Palo Alto, California, United States, 94304
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Swedish Medical Center
Englewood, Colorado, United States, 80113
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States, 06520
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Illinois
Rush University
Chicago, Illinois, United States, 60612
United States, Kentucky
Norton Neuroscience Institute
Louisville, Kentucky, United States, 40241
United States, Louisiana
Tulane Medical Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
University of Massachusetts Worcester
Worcester, Massachusetts, United States, 01655
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Spectrum Health Hospitals
Grand Rapids, Michigan, United States, 49506
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, New Mexico
The University of New Mexico Health Science Center
Albuquerque, New Mexico, United States, 87131
United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
Columbia University, New York - Presbyterian Hospital
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
United States, Oregon
Providence St Vincent Medical Center
Portland, Oregon, United States, 97225
United States, Pennsylvania
Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Tennessee
Erlanger Health System Baroness Hospital
Chattanooga, Tennessee, United States, 37403
United States, Texas
The University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
United States, Washington
Harborview Medical Center
Seattle, Washington, United States, 98104
Australia, New South Wales
Royal North Shore Hospital
Sydney, New South Wales, Australia, 2065
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Austria
Medizinische Universität Innsbruck
Innsbruck, Austria, A-6020
Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany, D-10117
Technische Universitat Dresden
Dresden, Germany, 01062
Universitätsklinikum Jena
Jena, Germany, 07747
LMU München, Klinikum Großhadern
Munich, Germany, 81377
Korea, Republic of
Keimyung University Dongsan Hospital
Daegu, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Seoul National University Bundang Hospital
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Switzerland
Universitätsspital Zürich
Zürich, Switzerland, 8091

Sponsors and Collaborators

C. R. Bard

Yale University

Boston University

Investigators

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Principal Investigator:	David M. Greer, MD, MA	Boston University
Principal Investigator:	Kevin N. Sheth, MD	Yale University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Review.

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Responsible Party:	C. R. Bard
ClinicalTrials.gov Identifier:	NCT02996266
Other Study ID Numbers:	BMD-1111
First Posted:	December 19, 2016 Key Record Dates
Last Update Posted:	June 21, 2022
Last Verified:	June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by C. R. Bard:


Targeted Temperature Management

Additional relevant MeSH terms:

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Ischemic Stroke Subarachnoid Hemorrhage Cerebral Hemorrhage Hemorrhage Fever Pathologic Processes Stroke Cerebrovascular Disorders	Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Body Temperature Changes Intracranial Hemorrhages

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