Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Condition: Fever
MeSH terms: Intracranial Hemorrhages; Hemorrhage; Fever; Hyperthermia
Intervention: Intravenous Ibuprofen; Acetaminophen (Standard of Care)
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; 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.
Intervention MeSH terms: Acetaminophen; Ibuprofen
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Fever reduction; Fever burden; intravenous ibuprofen

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.
    

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