Fever
Conditions
Keywords
Fever reduction, Fever burden, intravenous ibuprofen
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: 1. 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. 2. 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.
Interventions
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
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.
Sponsors
Cumberland Pharmaceuticals
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Fever Burden | Up to14 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Difference in Cost Between Ibuprofen and Acetaminophen | Up to 14 days | Cost analysis of aggressive fever control (AFC) between patients randomized to either intravenous ibuprofen infusion or standard of care (oral acetaminophen). |
| Bleeding Incidence | Up to 14 days | Incidence of bleeding (defined by a priori criteria) |
| Mean Difference in Inflammatory Markers | Up to 14 days | Mean difference in markers of inflammation between IV ibuprofen and standard of care groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Includes subjects from both arms. | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 35 |
| other Total, other adverse events | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
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.
Time frame: Up to14 days
Population: PI left before data could be analyzed and data collection was incomplete.
Secondary
Bleeding Incidence
Incidence of bleeding (defined by a priori criteria)
Time frame: Up to 14 days
Population: PI left before data could be analyzed and data collection was incomplete.
Secondary
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).
Time frame: Up to 14 days
Population: PI left before data could be analyzed and data collection was incomplete.
Secondary
Mean Difference in Inflammatory Markers
Mean difference in markers of inflammation between IV ibuprofen and standard of care groups
Time frame: Up to 14 days
Population: PI left before data could be analyzed and data collection was incomplete.