Efficacy of Bromocriptine For Fever Reduction in Acute Neurologic Injury
Condition: Subarachnoid Hemorrhage; Subdural Hematoma; Traumatic Brain Injury; Ischemic Stroke; Fever; Intracerebral Hemorrhage
MeSH terms: Brain Injuries; Ischemic Stroke; Brain Injuries, Traumatic; Subarachnoid Hemorrhage; Cerebral Hemorrhage; Hematoma, Subdural; Hemorrhage; Fever; Hematoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to evaluate the antipyretic effect of bromocriptine in
      critically-ill patients with acute neurologic injury and fever from infectious and
      non-infectious etiologies.
    

Detailed description: 
      In patients with acute neurologic injury such as subarachnoid hemorrhage (SAH), intracerebral
      hemorrhage (ICH), traumatic brain injury (TBI), subdural hematoma (SDH), and ischemic stroke,
      fever has been found to be an independent predictor of poor outcome including increased
      mortality rates, longer hospital stays, depressed level of consciousness, and worse
      functional outcomes. Our current antipyretic therapy of acetaminophen and sometimes
      nonsteroidal anti-inflammatory drugs are not very effective and external cooling requires
      sedatives and other medications to prevent shivering and pain. Bromocriptine is a dopamine D2
      receptor agonist which acts at the hypothalamus, a specific area of the brain that regulates
      body temperature. Fevers of both central and infectious etiologies must be regulated through
      the hypothalamus and we have evidence that bromocriptine has an antipyretic effect at the
      hypothalamus; thus, we hypothesize that bromocriptine could be used safely and more broadly
      to treat all fevers in the acute setting and not just refractory central fevers in this
      patient population.

      Here, we propose to evaluate the acute antipyretic effects of bromocriptine in this
      critically-ill population through a pilot, open label, blinded endpoint, randomized
      controlled trial. In both enrolling centers, University of California, San Francisco Medical
      Center Parnassus (UCSF) and Zuckerberg San Francisco General Hospital, every patient who is
      admitted to the neurointensive care unit for an anticipated stay of greater than 48 hours
      with a diagnosis of subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), traumatic
      brain injury (TBI), subdural hematoma (SDH), and ischemic stroke will be screened and
      consented. If they have a temperature reading ≥ 38.3 ºC, the investigational pharmacy will
      randomize them to the control arm of acetaminophen or the intervention arm of acetaminophen
      and bromocriptine for 48 hours. We will continuously measure their temperature and other
      vitals data. Retrospectively, we will review imaging and labs ordered to work up infectious
      etiologies of fever. The ICU nurse will do a 5 minute assessment every shift during the 48
      hour study period for side effects. The temperature data will be analyzed between the two
      study arms.
    

Intervention name(s): Bromocriptine 5 MG; Acetaminophen 650 MG
Intervention type(s): Drug; Drug
Intervention description(s): Bromocriptine 5 mg every 4 hours PO/NG/FT; Acetaminophen 650 mg every 4 hours PO/NG/FT for 48 hours
Other intervention name(s): parlodel; Tylenol
Intervention MeSH terms: Acetaminophen; Bromocriptine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: open label, blinded endpoint, randomized (1:1) controlled trial with two arms: control - acetaminophen and intervention - acetaminophen and bromocriptine.
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: fever; central fever; neurogenic fever; hyperthermia; bromocriptine; subarachnoid hemorrhage; SAH; subdural hematoma; SDH; intracerebral hemorrhage; ICH; traumatic brain injury; TBI; ischemic stroke