Ibuprofen Versus Acetaminophen for Treatment of Mild Traumatic Brain Injury (IVAMTBI)

• ClinicalTrials.gov Identifier: NCT02443142
• Recruitment Status: Unknown
• First Posted: May 13, 2015
• Last Update Posted: May 13, 2015
• Sponsor: Northwestern University
• Collaborator: Northwestern Memorial Hospital
• Information provided by (Responsible Party): Demetrios Kyriacou, Northwestern University

Study Description

Brief Summary:

Traumatic brain injury (TBI) is an important public health problem with an estimated 1.7 million new cases in the United States each year. Although the vast majority of these victims sustain mild TBI, many still develop headache, difficulty concentrating, and decreased memory with potential for serious long-term consequences. In particular, mild TBI is an important consequence of combat-related injuries sustained by military personnel and sports-related injuries in young adults. Unfortunately, treatment of mild TBI is usually limited to oral analgesics for headache pain such as acetaminophen (Tylenol) or ibuprofen (Motrin or Advil). Since there are no previous randomized trials of these medications for mild TBI, their comparative effectiveness is not known. Increasing animal based evidence suggests that mild TBI is related to brain cell injury caused by overexpression of a cellular enzyme (COX-2) that causes neuroinflammation. Fortunately, inhibition of COX-2 is easily achieved using ibuprofen. We hypothesize that head injured patients treated with ibuprofen will have a lower incidence of mild TBI symptoms than patients treated with acetaminophen. We will conduct a randomized clinical trial to measure the comparative effects of ibuprofen versus acetaminophen on the incidence of specific symptoms of mild TBI in emergency department patients with head injury.

Condition or disease	Intervention/treatment	Phase
Brain Concussion	Drug: Ibuprofen; Drug: Acetaminophen	Phase 2

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ibuprofen Versus Acetaminophen for Treatment of Mild Traumatic Brain Injury
• Study Start Date: May 2015
• Estimated Primary Completion Date: December 2015
• Estimated Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ibuprofen; Ibuprofen is a nonselective NSAID that inhibits both COX-1 and COX-2 isoenzymes. COX-2 inhibition prevents arachidonic acid from converting to vasoactive prostaglandins and reactive oxygen species in brain cell. The analgesic, antipyretic, and antiinflammatory activity of ibuprofen operates mainly through inhibition of COX-2. The experimental treatment oral doses of either ibuprofen (800 mg three times per day). Subjects will receive the first medication dose in the emergency department and will be given the remaining 5 doses to take over 48 hours as outpatients.	Drug: Ibuprofen; Ibuprofen 800 mg orally three times per day for two days for study subjects who are randomized to the ibuprofen arm.; Other Name: motrin
Active Comparator: Acetaminophen; Acetaminophen is a poor inhibitor of both COX isoenzymes in the CNS and has significantly weaker antiinflammatory effects than NSAIDs. Acetaminophen does not inhibit COX in peripheral tissues and is less effective in the presence of peroxides. The active comparator treatment is oral doses of acetaminophen (1000 mg three times per day). Subjects will receive the first medication dose in the emergency department and will be given the remaining 5 doses to take over 48 hours as outpatients.	Drug: Acetaminophen; Acetaminophen 1000 mg orrally three times per day for two days for subjects who are randomized to the acetaminophen arm.; Other Name: tylenol

Outcome Measures

Primary Outcome Measures :

1. Post-concussion symptoms [ Time Frame: 7 to 14 days after enrollment. ]
   The main outcome variables will be the incidence of post-concussion symptoms that will be measured using NIH Common Data Elements and Neuro-QOL instruments. The Neuro-QOL instruments were developed for the NIH by the Northwestern University Department of Medical Social Sciences to provide clinically relevant and psychometrically robust health-related quality of life assessment tools for patients with common neurological disorders. In addition, the Neuro-QOL measurement system provides item banks and short forms that enable patient reported outcome measurement in neurological research which minimizes patient burden.41-44 This information will be collected at 7 to 14 days after initial ED evaluation. Emphasis will be placed on the Neuro-QOL instruments that measure headache pain and cognitive function as these are the most common and concerning symptoms of mild TBI.

Secondary Outcome Measures :

1. Adverse drug reactions [ Time Frame: 7 to 14 days after enrollment ]
   Information regarding adverse drug reactions (ADRs) will also be obtained during the follow up interview of the study subjects. This assessment will include questions regarding abdominal pain or discomfort and any allergic reaction (e.g., rash, swelling, or difficulty breathing).

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Closed head injury within the past 24 hours with history (loss of consciousness, amnesia, mechanism of injury such as motor vehicle collision or fall from height) or specific symptoms and signs (headache, vomiting, dizziness, head injury, short-term memory deficit, confusion, blurred vision, balance problems) that prompts computerized tomography (CT) brain evaluation as determined by an emergency physician.
2. Age 21 through 60 years of age.
3. Initial Glasgow Coma Score of 13 or greater at time of ED presentation with normal neurologic examination and Glasgow Coma Score of 15 within two hours of initial assessment.
4. Normal neurologic examination in the emergency department except for symptoms and signs described above (e.g., no focal neurologic deficit).
5. Normal brain and skull on CT scan in the ED.
6. Working cellular phone (for follow up assessment).

Exclusion Criteria:

1. Significant concomitant non-cranial injury requiring pain medication (e.g., facial fracture, severe extremity injury, major blunt trauma.)
2. Any type of skull or cervical spine fracture.
3. Post-traumatic seizure.
4. Currently taking NSAIDS, acetaminophen, or other pain medications on a regular basis.
5. Currently taking ANY coagulant medication (e.g., Plavix, aspirin, Xeralto, Coumadin).
6. Any bleeding disorder, predisposition to bleeding, or history of gastrointestinal bleeding.
7. Pregnancy.
8. Clinical intoxication with alcohol or illicit medication.
9. Chronic alcohol abuse.
10. Any liver or renal dysfunction or failure.
11. Justification of obtaining CT brain evaluation that included patient being intoxicated.
12. Intolerance, allergy or adverse reaction to either ibuprofen or acetaminophen.
13. Any current or previously diagnosed cardiovascular condition (e.g., hypertension, coronary arterial disease, myocardial infarct, angina, congestive heart failure, pulmonary embolism, deep venous thrombosis).
14. Any current or previously diagnosed neurovascular condition (e.g., stroke, TIA, multiple sclerosis, seizure disorder).
15. Any active cancer or malignancy.

Contacts and Locations

Contacts

Contact: Ryan McConnell, BA; 312 694 7000; rmcconn1@nm.org

Locations

United States, Illinois

Northwestern University Feinberg School of Medicine; Not yet recruiting

Chicago, Illinois, United States, 60045

Contact: Ryan McConnell 312-694-7000 rmcconn1@nm.org

Sponsors and Collaborators

Northwestern University

Northwestern Memorial Hospital

Investigators

• Principal Investigator: Demetrios N. Kyriacou, MD,PhD; Northwestern University

More Information

• Responsible Party: Demetrios Kyriacou, Principal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT02443142 History of Changes
• Other Study ID Numbers: NorthwesternU
• First Posted: May 13, 2015
• Last Update Posted: May 13, 2015
• Last Verified: March 2015

Keywords provided by Demetrios Kyriacou, Northwestern University:

mild TBI; concussion; post-concussion syndrome

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Head Injuries, Closed; Wounds, Nonpenetrating; 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