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

NCT01530880 | Terminated Phase 4 Results

• 1 other identifier: AAAI1788
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Fever

Keywords

Fever reduction; Fever burden; intravenous ibuprofen

Outcome Measures

Primary Outcomes (1)

• Prevalence of Fever Burden

  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.

  Up to14 days

Secondary Outcomes (3)

• Mean Difference in Inflammatory Markers

  Up to 14 days

• Difference in Cost Between Ibuprofen and Acetaminophen

  Up to 14 days

• Bleeding Incidence

  Up to 14 days

Study Arms (2)

Intravenous Ibuprofen

EXPERIMENTAL

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

Standard of Care

OTHER

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)

Interventions

Intravenous Ibuprofen DRUG

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

Also known as: Caldolor

Intravenous Ibuprofen

Acetaminophen (Standard of Care) DRUG

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.

Also known as: Tylenol

Standard of Care

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• Cumberland Pharmaceuticals: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Fever

Interventions

Ibuprofen; Acetaminophen; Standard of Care

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Michael Schmidt
• Organization: Columbia University

mjs2134@columbia.edu

212-305-8745

Study Officials

• J. Michael Schmidt, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2012
• First Posted: February 10, 2012
• Study Start: October 1, 2012
• Primary Completion: March 17, 2016
• Study Completion: March 17, 2016
• Last Updated: August 28, 2017
• Results First Posted: August 28, 2017

Record last verified: 2017-08

Locations

US (1)