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Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage

This study has been terminated.
(PI no longer at institution)
Sponsor:
Collaborator:
Cumberland Pharmaceuticals
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT01530880
First received: February 8, 2012
Last updated: August 15, 2017
Last verified: August 2017
  Purpose

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.


Condition Intervention Phase
Fever Drug: Intravenous Ibuprofen Drug: Acetaminophen (Standard of Care) Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Prevalence of Fever Burden [ Time Frame: 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 Outcome Measures:
  • Mean Difference in Inflammatory Markers [ Time Frame: Up to 14 days ]
    Mean difference in markers of inflammation between IV ibuprofen and standard of care groups

  • Difference in Cost Between Ibuprofen and Acetaminophen [ Time Frame: 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 [ Time Frame: Up to 14 days ]
    Incidence of bleeding (defined by a priori criteria)


Enrollment: 35
Study Start Date: October 2012
Study Completion Date: March 17, 2016
Primary Completion Date: March 17, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intravenous Ibuprofen
Patients assigned to the ibuprofen treatment group will receive a 400 mg IV ibuprofen bolus over 30 minutes followed by an infusion of ibuprofen at 85 mg/hr.
Drug: Intravenous Ibuprofen
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
Other Name: Caldolor
Standard of Care
Patients assigned to the standard of care group will be given 650 mg of oral acetaminophen and continue to receive 650 mg of oral acetaminophen every 6 hours as needed to maintain temperature < 38.3 C (100.9 F).
Drug: Acetaminophen (Standard of 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.
Other Name: Tylenol

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01530880

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Cumberland Pharmaceuticals
Investigators
Principal Investigator: J. Michael Schmidt, MD Columbia University
  More Information

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT01530880     History of Changes
Other Study ID Numbers: AAAI1788
Study First Received: February 8, 2012
Results First Received: July 14, 2017
Last Updated: August 15, 2017

Keywords provided by Columbia University:
Fever reduction
Fever burden
intravenous ibuprofen

Additional relevant MeSH terms:
Hemorrhage
Fever
Intracranial Hemorrhages
Pathologic Processes
Body Temperature Changes
Signs and Symptoms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Acetaminophen
Ibuprofen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2017