Efficacy of Bromocriptine For Fever Reduction in Acute Neurologic Injury (BFF)

June 22, 2021 updated by: University of California, San Francisco

Efficacy of Bromocriptine to Reduce Body Temperature in Febrile Critically-ill Adults With Acute Neurologic Disease: an Open-label, Blinded Endpoint, Randomized Controlled Trial

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • San Francisco, California, United States, 94110
        • Zuckerberg San Francisco General Hospital and Trauma Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco Medical Center - Parnassus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age ≥18 years old
  • weight ≥ 40 kg
  • one reading of body temperature ≥ 38.3 ºC
  • diagnosis of subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury, subdural hematoma, or ischemic stroke
  • admission to the Intensive Care Unit at UCSF Medical Center or Zuckerberg San Francisco General Hospital.

Exclusion Criteria:

  • bromocriptine or acetaminophen hypersensitivity or allergy
  • known contraindication to bromocriptine- known ergot alkaloid hypersensitivity, known history of syncopal migraine
  • contraindication to nasogastric tube or swallowing pills
  • current diagnosis of acute liver failure, acute liver injury, or prior diagnosis of cirrhosis. acute presentation (< 26 weeks), evidence of coagulation abnormality: international normalized ratio (INR) ≥ 2; evidence of liver damage: alanine aminotransferase (ALT) of 10 x normal value; and any degree of mental status alteration
  • currently being treated with intra or extravascular therapeutic hypothermia - or where therapeutic hypothermia treatment is anticipated during study period
  • hyperthermic syndromes: heat stroke, evidence of thyrotoxicosis, malignant hyperthermia, neuroleptic malignant syndrome, or other drug-induced hyperthermia
  • administration of acetaminophen or acetaminophen containing medications within 9 hours prior to fever presentation
  • administration of non-steroidal anti-inflammatory drugs (NSAIDs) within 6 hours prior to fever presentation or aspirin > 300mg less than 1 hour prior to fever presentation.
  • pregnancy
  • extracorporeal blood circuit therapies: replacement therapy, extracorporeal life support (ventricular assist device, extracorporeal membrane oxygenation) during study period
  • anticipated ICU stay < 48 hours'
  • creatinine clearance ≤ 30
  • severe cardiovascular disease (especially unstable angina or severe valvular disease)
  • patients already taking bromocriptine for other indications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Acetaminophen
Standard of care - acetaminophen 650mg every 4 hours PO/NG/FT (per oral, nasogastric tube, feeding tube) for 48 hours, initiated within 1 hour after temperature reading ≥ 38.3ºC.
Acetaminophen 650 mg every 4 hours PO/NG/FT for 48 hours
Other Names:
  • Tylenol
Experimental: Bromocriptine and Acetaminophen
Bromocriptine 5mg every 4 hours PO/NG/FT for 48 hours and acetaminophen 650mg every 4 hours PO/NG/FT for 48 hours, initiated within 1 hour after temperature reading ≥ 38.3ºC.
Acetaminophen 650 mg every 4 hours PO/NG/FT for 48 hours
Other Names:
  • Tylenol
Bromocriptine 5 mg every 4 hours PO/NG/FT
Other Names:
  • parlodel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Temperature Burden
Time Frame: over 48 hours
Mean total body temperature burden above 37°C over 48 hours during which patient receives either control or intervention medication.
over 48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events - Symptomatic Hypotension, Nausea and Headache
Time Frame: Nursing assessment at every shift during 48 hour study period after first drug administration
Episodes of symptomatic hypotension, including decrease in supine systolic and diastolic pressures of greater than 20mm and 10mm Hg respectively with patient reported accompanying symptoms of light headedness or dizziness and incidence of nausea and headache.
Nursing assessment at every shift during 48 hour study period after first drug administration
Total Time That Temperature is ≥ 38.3ºC
Time Frame: 48 hours
Time in minutes where the temperature is ≥ 38.3ºC during the 48 hours of control versus intervention administration.
48 hours
Total Time to First Temperature < 37.5ºC
Time Frame: 48 hours
Time in minutes it took after medication administration for the temperature to reach < 37.5ºC.
48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Judy H Ch'ang, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2018

Primary Completion (Actual)

November 2, 2019

Study Completion (Actual)

November 2, 2019

Study Registration Dates

First Submitted

March 17, 2018

First Submitted That Met QC Criteria

April 5, 2018

First Posted (Actual)

April 12, 2018

Study Record Updates

Last Update Posted (Actual)

June 24, 2021

Last Update Submitted That Met QC Criteria

June 22, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is no plan to make IPD available to other researchers as this data is very specific to this study.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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