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

Fever Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01530880
• Other study ID #: AAAI1788
• Status: Recruiting
• Phase: Phase 4
• First received: February 8, 2012
• Last updated: November 13, 2012
• Start date: February 2012
• Est. completion date: May 2013

Study information

• Verified date: November 2012
• Source: Columbia University
• Contact: Neeraj Badjatia, MD
• Phone: 212-305-7236
• Email: nb2217[@]columbia.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years of age or older

• Aneurysmal subarachnoid hemorrhage (SAH), Hunt Hess grade >= 3, 24 hours after admission.

• Intracerebral hemorrhage (ICH), GCS < 10

• Presence of intraventricular hemorrhage on initial brain CT scan

Exclusion Criteria:

• Imminent death within 72 hours of admission.

• Plan for discharge from the Neuro ICU within 72 hours of admission.

• Diagnosis with sepsis (SIRS criteria plus the presence of known or suspected infection)

• Presence of coagulopathy (INR > 1.7)

• Thrombocytopenia (platelet count < 100,000)

• History of gastrointestinal bleed

• Abnormal liver function tests (AST/ALT/AP/GGT 2x normal)

• Hypersensitivity to ibuprofen

• Pregnancy as determined by urine beta Hcg, or lactating post partum women

• Renal impairment (Cr > 1.5 mg/dL)

• Measured body weight < 50 kg

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Fever

Intervention

Drug:
• Intravenous Ibuprofen
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
• 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.

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Cumberland Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Inflammatory Markers	Mean difference in markers of inflammation between IV ibuprofen and standard of care groups	Up to 14 days	No
Secondary	Cost analysis	Cost analysis of aggressive fever control (AFC) between patients randomized to either intravenous ibuprofen infusion or standard of care (oral acetaminophen).	Up to 14 days	No
Secondary	Bleeding Incidence	Incidence of bleeding (defined by a priori criteria)	Up to 14 days	Yes