Efficacy of Bromocriptine For Fever Reduction in Acute Neurologic Injury

NCT03496545 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 18-24766
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Subarachnoid Hemorrhage; Subdural Hematoma; Traumatic Brain Injury; Ischemic Stroke; Fever; Intracerebral Hemorrhage

Keywords

fever; central fever; neurogenic fever; hyperthermia; bromocriptine; subarachnoid hemorrhage; SAH; subdural hematoma; SDH; intracerebral hemorrhage; ICH; traumatic brain injury; TBI; ischemic stroke

Outcome Measures

Primary Outcomes (1)

• Temperature Burden

  Mean total body temperature burden above 37°C over 48 hours during which patient receives either control or intervention medication.

  over 48 hours

Secondary Outcomes (3)

• Incidence of Adverse Events - Symptomatic Hypotension, Nausea and Headache

  Nursing assessment at every shift during 48 hour study period after first drug administration

• Total Time That Temperature is ≥ 38.3ºC

  48 hours

• Total Time to First Temperature < 37.5ºC

  48 hours

Study Arms (2)

Acetaminophen

ACTIVE COMPARATOR

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.

Drug: Acetaminophen 650 MG

Bromocriptine and Acetaminophen

EXPERIMENTAL

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.

Drug: Bromocriptine 5 MG; Drug: Acetaminophen 650 MG

Interventions

Bromocriptine 5 MG DRUG

Bromocriptine 5 mg every 4 hours PO/NG/FT

Also known as: parlodel

Bromocriptine and Acetaminophen

Acetaminophen 650 MG DRUG

Acetaminophen 650 mg every 4 hours PO/NG/FT for 48 hours

Also known as: Tylenol

Acetaminophen; Bromocriptine and Acetaminophen

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (2)

Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, 94110, United States

Location

University of California, San Francisco Medical Center - Parnassus

San Francisco, California, 94143, United States

Location

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MeSH Terms

Conditions

Subarachnoid Hemorrhage; Hematoma, Subdural; Brain Injuries, Traumatic; Ischemic Stroke; Fever; Cerebral Hemorrhage; Hyperthermia

Interventions

Bromocriptine; Acetaminophen

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Hemorrhage, Traumatic; Craniocerebral Trauma; Trauma, Nervous System; Hematoma; Wounds and Injuries; Brain Injuries; Stroke; Body Temperature Changes; Signs and Symptoms; Heat Stress Disorders

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Judy Ch'ang, MD
• Organization: Weill Cornell Medicine

jhc9010@med.cornell.edu

(212) 746-2596

Study Officials

• Judy H Ch'ang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The data analyst who will analyze the data from each patient will be masked to what medication(s) the patients received.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label, blinded endpoint, randomized (1:1) controlled trial with two arms: control - acetaminophen and intervention - acetaminophen and bromocriptine.

Study Record Dates

• First Submitted: March 17, 2018
• First Posted: April 12, 2018
• Study Start: November 30, 2018
• Primary Completion: November 2, 2019
• Study Completion: November 2, 2019
• Last Updated: June 24, 2021
• Results First Posted: June 24, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)