Back to resultsAggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Primary Purpose
Fever
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Intravenous Ibuprofen
Acetaminophen (Standard of Care)
Sponsored by
About this trial
This is an interventional treatment trial for Fever focused on measuring Fever reduction, Fever burden, intravenous ibuprofen
Eligibility Criteria
Inclusion Criteria:
- 18 years of age or older
- Aneurysmal subarachnoid hemorrhage (SAH), Hunt Hess grade >= 3, 24 hours after admission.
- Intracerebral hemorrhage (ICH), Glasgow Coma Scale (GCS) < 10
- Presence of intraventricular hemorrhage on initial brain computerized tomography (CT) scan
Exclusion Criteria:
- Imminent death within 72 hours of admission.
- Plan for discharge from the Neuro intensive care unit (ICU) within 72 hours of admission.
- Diagnosis with sepsis (Systemic inflammatory response syndrome (SIRS) criteria plus the presence of known or suspected infection)
- Presence of coagulopathy (international normalized ratio (INR) > 1.7)
- Thrombocytopenia (platelet count < 100,000)
- History of gastrointestinal bleed
- Abnormal liver function tests (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (AP)/Gamma-glutamyl transferase (GGT) 2x normal)
- Hypersensitivity to ibuprofen
- Pregnancy as determined by urine beta human chorionic gonadotropin (hCG), or lactating postpartum women
- Renal impairment (Creatinine > 1.5 mg/dL)
- Measured body weight < 50 kg
Sites / Locations
- Columbia University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Intravenous Ibuprofen
Standard of Care
Arm Description
Patients assigned to the ibuprofen treatment group will receive a 400 mg IV ibuprofen bolus over 30 minutes followed by an infusion of ibuprofen at 85 mg/hr.
Patients assigned to the standard of care group will be given 650 mg of oral acetaminophen and continue to receive 650 mg of oral acetaminophen every 6 hours as needed to maintain temperature < 38.3 C (100.9 F).
Outcomes
Primary Outcome Measures
Prevalence of Fever Burden
Reduction in fever burden (degrees C x hours) with intravenous ibuprofen infusion as compared to oral acetaminophen over duration of treatment. Fever burden is calculated hourly by subtracting each patient's recorded temperature (from either a bladder or esophageal temperature probe) from 37 degrees C.
Secondary Outcome Measures
Mean Difference in Inflammatory Markers
Mean difference in markers of inflammation between IV ibuprofen and standard of care groups
Difference in Cost Between Ibuprofen and Acetaminophen
Cost analysis of aggressive fever control (AFC) between patients randomized to either intravenous ibuprofen infusion or standard of care (oral acetaminophen).
Bleeding Incidence
Incidence of bleeding (defined by a priori criteria)
Full Information
NCT ID
NCT01530880
First Posted
February 8, 2012
Last Updated
August 15, 2017
Sponsor
Columbia University
Collaborators
Cumberland Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01530880
Brief Title
Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Official Title
Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
PI no longer at institution
Study Start Date
October 2012 (undefined)
Primary Completion Date
March 17, 2016 (Actual)
Study Completion Date
March 17, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Columbia University
Collaborators
Cumberland Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Fever, defined as temperature higher than 38.3C (100.9 F), is common in patients with head injuries and is associated with poor recovery after injury. The current standard of care is to use oral acetaminophen (Tylenol) followed by a body cooling device. This method can effectively reduce fever but results in a high rate of shivering. Shivering is stressful to the heart and can further worsen brain injury. Methods to combat shivering have been developed and are successful in limiting the stress in the majority of patients that use a body cooling device. However, the drugs used to control shivering are sedating and may also interfere with brain recovery.
The purpose of this study is to assess whether ibuprofen given intravenously is more effective in combating fever than the current standard of care. Should results from this study demonstrate that ibuprofen infusion is effective, a larger study will be conducted to determine whether this aggressive fever control regimen leads to improved recovery after brain injury.
Detailed Description
This is an open-label, investigator initiated single center, randomized, prospective study. Subjects meeting enrollment criteria will be randomly assigned 1:1 to one of two groups:
Standard Care: Acetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
Ibuprofen 400 mg/100 mL NS IV over 30 minutes, followed by a continuous infusion of 2000 mg/500 mL NS at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
Patients/surrogates will be approached for consent and randomized upon admission. Therapy will only be initiated once a patient becomes febrile (>=38.3 C, 100.9 F). The use of temperature modulating devices will be permitted as per institutionally approved guidelines in those patients continuing to demonstrate a fever (T>38.3 C, 100.9 F) with either therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fever
Keywords
Fever reduction, Fever burden, intravenous ibuprofen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous Ibuprofen
Arm Type
Experimental
Arm Description
Patients assigned to the ibuprofen treatment group will receive a 400 mg IV ibuprofen bolus over 30 minutes followed by an infusion of ibuprofen at 85 mg/hr.
Arm Title
Standard of Care
Arm Type
Other
Arm Description
Patients assigned to the standard of care group will be given 650 mg of oral acetaminophen and continue to receive 650 mg of oral acetaminophen every 6 hours as needed to maintain temperature < 38.3 C (100.9 F).
Intervention Type
Drug
Intervention Name(s)
Intravenous Ibuprofen
Other Intervention Name(s)
Caldolor
Intervention Description
Ibuprofen 400 mg/100 mL intravenous (IV) over 30 minutes, followed by a continuous infusion of 2000 mg/500 mL at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first
Intervention Type
Drug
Intervention Name(s)
Acetaminophen (Standard of Care)
Other Intervention Name(s)
Tylenol
Intervention Description
Acetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
Primary Outcome Measure Information:
Title
Prevalence of Fever Burden
Description
Reduction in fever burden (degrees C x hours) with intravenous ibuprofen infusion as compared to oral acetaminophen over duration of treatment. Fever burden is calculated hourly by subtracting each patient's recorded temperature (from either a bladder or esophageal temperature probe) from 37 degrees C.
Time Frame
Up to14 days
Secondary Outcome Measure Information:
Title
Mean Difference in Inflammatory Markers
Description
Mean difference in markers of inflammation between IV ibuprofen and standard of care groups
Time Frame
Up to 14 days
Title
Difference in Cost Between Ibuprofen and Acetaminophen
Description
Cost analysis of aggressive fever control (AFC) between patients randomized to either intravenous ibuprofen infusion or standard of care (oral acetaminophen).
Time Frame
Up to 14 days
Title
Bleeding Incidence
Description
Incidence of bleeding (defined by a priori criteria)
Time Frame
Up to 14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years of age or older
Aneurysmal subarachnoid hemorrhage (SAH), Hunt Hess grade >= 3, 24 hours after admission.
Intracerebral hemorrhage (ICH), Glasgow Coma Scale (GCS) < 10
Presence of intraventricular hemorrhage on initial brain computerized tomography (CT) scan
Exclusion Criteria:
Imminent death within 72 hours of admission.
Plan for discharge from the Neuro intensive care unit (ICU) within 72 hours of admission.
Diagnosis with sepsis (Systemic inflammatory response syndrome (SIRS) criteria plus the presence of known or suspected infection)
Presence of coagulopathy (international normalized ratio (INR) > 1.7)
Thrombocytopenia (platelet count < 100,000)
History of gastrointestinal bleed
Abnormal liver function tests (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (AP)/Gamma-glutamyl transferase (GGT) 2x normal)
Hypersensitivity to ibuprofen
Pregnancy as determined by urine beta human chorionic gonadotropin (hCG), or lactating postpartum women
Renal impairment (Creatinine > 1.5 mg/dL)
Measured body weight < 50 kg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J. Michael Schmidt, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
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Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
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