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

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ClinicalTrials.gov Identifier: NCT01530880
Recruitment Status : Terminated (PI no longer at institution)
First Posted : February 10, 2012
Results First Posted : August 28, 2017
Last Update Posted : August 28, 2017
Sponsor:
Collaborator:
Cumberland Pharmaceuticals
Information provided by (Responsible Party):
Columbia University

Tracking Information
First Submitted Date  ICMJE February 8, 2012
First Posted Date  ICMJE February 10, 2012
Results First Submitted Date  ICMJE July 14, 2017
Results First Posted Date  ICMJE August 28, 2017
Last Update Posted Date August 28, 2017
Study Start Date  ICMJE October 2012
Actual Primary Completion Date March 17, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2012)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2012)
  • Inflammatory Markers [ Time Frame: Up to 14 days ]
    Mean difference in markers of inflammation between IV ibuprofen and standard of care groups
  • Cost analysis [ 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Official Title  ICMJE Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Brief 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fever
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Intravenous Ibuprofen
  • 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).
    Intervention: Drug: Acetaminophen (Standard of Care)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 15, 2017)
35
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2012)
50
Actual Study Completion Date  ICMJE March 17, 2016
Actual Primary Completion Date March 17, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01530880
Other Study ID Numbers  ICMJE AAAI1788
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Cumberland Pharmaceuticals
Investigators  ICMJE
Principal Investigator: J. Michael Schmidt, MD Columbia University
PRS Account Columbia University
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP