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Impact of Fever Prevention in Brain Injured Patients (INTREPID)

Primary Purpose

Fever, Ischemic Stroke, Intracerebral Hemorrhage

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Targeted Temperature Management
Standard Care
Sponsored by
C. R. Bard
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fever focused on measuring Targeted Temperature Management

Eligibility Criteria

21 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Southern California
  • Stanford University Hospital
  • University of Colorado Hospital
  • Swedish Medical Center
  • Yale New Haven Hospital
  • University of Florida
  • Rush University
  • Norton Neuroscience Institute
  • Tulane Medical Center
  • University of Maryland Medical Center
  • Boston University Medical Center
  • University of Massachusetts Worcester
  • Henry Ford Hospital
  • Spectrum Health Hospitals
  • Washington University
  • The University of New Mexico Health Science Center
  • Mount Sinai Hospital
  • Columbia University, New York - Presbyterian Hospital
  • Duke University Medical Center
  • Wake Forest University Health Sciences
  • Ohio State University Wexner Medical Center
  • Riverside Methodist Hospital
  • Providence St Vincent Medical Center
  • Hershey Medical Center
  • Rhode Island Hospital
  • Erlanger Health System Baroness Hospital
  • The University of Texas Health Science Center at Houston
  • Harborview Medical Center
  • Royal North Shore Hospital
  • Royal Adelaide Hospital
  • Medizinische Universität Innsbruck
  • Charité - Universitätsmedizin Berlin
  • Technische Universitat Dresden
  • Universitätsklinikum Jena
  • LMU München, Klinikum Großhadern
  • Keimyung University Dongsan Hospital
  • Asan Medical Center
  • Seoul National University Bundang Hospital
  • Seoul National University Hospital
  • Universitätsspital Zürich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Fever Prevention

Standard Care

Arm Description

Fever will be prevented using a surface targeted temperature management system

Standard care in which fever may spontaneously develop

Outcomes

Primary Outcome Measures

Fever Burden
Daily average fever burden (°C-hour)

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Adverse Events
An untoward medical occurrence, unintended disease or injury, or unanticipated complication
Major Adverse Events
MAEs defined as one of the following: pneumonia, sepsis, malignant cerebral edema, death
Number of Participants With Infection
Healthcare associated infection
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.

Full Information

First Posted
December 5, 2016
Last Updated
August 25, 2023
Sponsor
C. R. Bard
Collaborators
Yale University, Boston University
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1. Study Identification

Unique Protocol Identification Number
NCT02996266
Brief Title
Impact of Fever Prevention in Brain Injured Patients
Acronym
INTREPID
Official Title
Impact of Fever Prevention in Brain Injured Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Futility
Study Start Date
January 2017 (Actual)
Primary Completion Date
May 12, 2022 (Actual)
Study Completion Date
May 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
C. R. Bard
Collaborators
Yale University, Boston University

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fever, Ischemic Stroke, Intracerebral Hemorrhage, Subarachnoid Hemorrhage
Keywords
Targeted Temperature Management

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
686 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fever Prevention
Arm Type
Experimental
Arm Description
Fever will be prevented using a surface targeted temperature management system
Arm Title
Standard Care
Arm Type
Active Comparator
Arm Description
Standard care in which fever may spontaneously develop
Intervention Type
Device
Intervention Name(s)
Targeted Temperature Management
Other Intervention Name(s)
Arctic Sun 5000 Temperature Management System
Intervention Description
Prophylactic normothermia
Intervention Type
Other
Intervention Name(s)
Standard Care
Intervention Description
No intervention to control temperature unless fever occurs
Primary Outcome Measure Information:
Title
Fever Burden
Description
Daily average fever burden (°C-hour)
Time Frame
Up to 14 days
Secondary Outcome Measure Information:
Title
Primary Neurologic Outcome: Modified Rankin Scale Short-Term
Description
Modified Rankin Scale is a 6-category outcome measurement with 0 = no limitations, no symptoms and 6 = death.
Time Frame
3-months post injury
Title
Other Neurologic Outcomes: NIH Stroke Scale Short-Term
Description
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.
Time Frame
3-months post injury
Title
Other Neurologic Outcomes: Barthel Index Short-Term
Description
Barthel Index is an assessment of functional independence. Scores range from 0 to 100, with lower scores indicating worse outcome.
Time Frame
3-months post injury
Title
Other Neurologic Outcomes: Glasgow Outcome Scale Extended Short-Term
Description
Glasgow Outcome Scale assesses functional outcome after acute brain injury. Scores range from 1-8, with lower scores indicating worse outcome.
Time Frame
3-months post injury
Title
Other Neurologic Outcomes: Montreal Cognitive Assessment Short-Term
Description
Montreal Cognitive Assessment assesses for cognitive impairment. Scores range from 0-30, with lower scores indicating worse outcome.
Time Frame
3-months post injury
Title
Primary Neurologic Outcome: Modified Rankin Scale Mid-Term
Description
Modified Rankin Scale is a 6-category outcome measurement with 0 = no limitations, no symptoms and 6 = death.
Time Frame
6-months post injury
Title
Other Neurologic Outcomes: NIH Stroke Scale Mid-Term
Description
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.
Time Frame
6-months post injury
Title
Other Neurologic Outcomes: Barthel Index Mid-Term
Description
Barthel Index is an assessment of functional independence. Scores range from 0 to 100, with lower scores indicating worse outcome.
Time Frame
6-months post injury
Title
Other Neurologic Outcomes: Glasgow Outcome Scale Extended Mid-Term
Description
Glasgow Outcome Scale assesses functional outcome after acute brain injury. Scores range from 1-8, with lower scores indicating worse outcome.
Time Frame
6-months post injury
Title
Other Neurologic Outcomes: Montreal Cognitive Assessment Mid-Term
Description
Montreal Cognitive Assessment assesses for cognitive impairment. Scores range from 0-30, with lower scores indicating worse outcome.
Time Frame
6-months post injury
Title
Primary Neurologic Outcome: Modified Rankin Scale Long-Term
Description
Modified Rankin Scale is a 6-category outcome measurement with 0 = no limitations, no symptoms and 6 = death.
Time Frame
12-months post injury
Title
Adverse Events
Description
An untoward medical occurrence, unintended disease or injury, or unanticipated complication
Time Frame
From date of randomization until hospital discharge, assessed up to 30 days
Title
Major Adverse Events
Description
MAEs defined as one of the following: pneumonia, sepsis, malignant cerebral edema, death
Time Frame
From date of randomization until end of study, assessed up to 12 months
Title
Number of Participants With Infection
Description
Healthcare associated infection
Time Frame
From date of randomization until hospital discharge, assessed up to 30 days
Title
Number of Subjects With Shivering
Description
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.
Time Frame
Up to 14 days
Other Pre-specified Outcome Measures:
Title
Hospital Length of Stay
Description
Overall hospitalization duration
Time Frame
From date of randomization until hospital discharge, assessed up to 90 days
Title
ICU Length of Stay
Description
ICU Duration
Time Frame
From date of randomization until ICU discharge
Title
Mortality
Description
Mortality
Time Frame
7-day (or hospital discharge); 3-, 6-, and 12-months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David M. Greer, MD, MA
Organizational Affiliation
Boston University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kevin N. Sheth, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford University Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Swedish Medical Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Rush University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Norton Neuroscience Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40241
Country
United States
Facility Name
Tulane Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Massachusetts Worcester
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Spectrum Health Hospitals
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49506
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The University of New Mexico Health Science Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University, New York - Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Riverside Methodist Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
Providence St Vincent Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Erlanger Health System Baroness Hospital
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Royal North Shore Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Medizinische Universität Innsbruck
City
Innsbruck
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
D-10117
Country
Germany
Facility Name
Technische Universitat Dresden
City
Dresden
ZIP/Postal Code
01062
Country
Germany
Facility Name
Universitätsklinikum Jena
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
LMU München, Klinikum Großhadern
City
Munich
ZIP/Postal Code
81377
Country
Germany
Facility Name
Keimyung University Dongsan Hospital
City
Daegu
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Universitätsspital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33761119
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.
Results Reference
derived
PubMed Identifier
32562686
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.
Results Reference
derived

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Impact of Fever Prevention in Brain Injured Patients

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