Ibuprofen Versus Acetaminophen for Treatment of Mild Traumatic Brain Injury

NCT02443142 | Withdrawn Phase 2

• 1 other identifier: NorthwesternU
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Concussion

Keywords

mild TBI; concussion; post-concussion syndrome

Outcome Measures

Primary Outcomes (1)

• Post-concussion symptoms

  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.

  7 to 14 days after enrollment.

Secondary Outcomes (1)

• Adverse drug reactions

  7 to 14 days after enrollment

Study Arms (2)

Ibuprofen

EXPERIMENTAL

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

Acetaminophen

ACTIVE COMPARATOR

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

Interventions

Ibuprofen DRUG

Ibuprofen 800 mg orally three times per day for two days for study subjects who are randomized to the ibuprofen arm.

Also known as: motrin

Ibuprofen

Acetaminophen DRUG

Acetaminophen 1000 mg orrally three times per day for two days for subjects who are randomized to the acetaminophen arm.

Also known as: tylenol

Acetaminophen

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Age 21 through 60 years of age.
• 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.
• Normal neurologic examination in the emergency department except for symptoms and signs described above (e.g., no focal neurologic deficit).
• Normal brain and skull on CT scan in the ED.
• Working cellular phone (for follow up assessment).

You may not qualify if:

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

Sponsors & Collaborators

• Northwestern University: lead
• Northwestern Memorial Hospital: collaborator

Study Sites (1)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60045, United States

Location

MeSH Terms

Conditions

Brain Concussion; Post-Concussion Syndrome

Interventions

Ibuprofen; Acetaminophen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Study Officials

• Demetrios N. Kyriacou, MD,PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 13, 2020

Record last verified: 2015-03

Locations

US (1)