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

NCT ID: NCT01530880

Last Updated: 2017-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-03-17

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.

Conditions

Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Intravenous Ibuprofen

Intervention Type: 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

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).

Group Type: OTHER

Acetaminophen (Standard of Care)

Intervention Type: 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.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Caldolor; Tylenol

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cumberland Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J. Michael Schmidt, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAI1788

Identifier Type: -

Identifier Source: org_study_id