A Comparative Efficacy Trial of IV Acetaminophen Versus IV Ketorolac for Emergency Department Treatment of Generalized Headache

Study Overview
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Brief Summary
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This randomized, double-blind trial will compare the clinical efficacy of IV acetaminophen to that of IV ketorolac as adjuncts to standard therapy (prochlorperazine and diphenhydramine) in the treatment of patients presenting to the emergency department with chief complaint of headache or variants thereof.

Detailed Description
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After initial assessment of the patient by the provider, including careful review of inclusion and exclusion criteria, informed consent will be obtained. If a patient does not wish to participate in this study, he/she will receive alternative treatment at the discretion of their ED provider. The provider will place orders in the electronic medical record for Headache study order set. This order set includes Compazine® 10 mg IV, Benadryl® 25 mg IV, and study drug. Pharmacy will receive the order for the study drug. The research pharmacist will randomly assign participants to group A (1000 mg Ofirmev®) or group B (15 mg ketorolac). He/she will fill medication vials and IV bags in each study kit. The kit for group A will contain a 100mL bag containing 1000 mg acetaminophen and a placebo vial of normal saline as well as both Compazine® and Benadryl®. The kit for group B will contain 100mL 0.9% normal saline and a vial containing 15 mg ketorolac as well as Compazine® and Benadryl®. The study kit will be sent to the emergency department via the tube system. When the study kit arrives, he/she will give each patient Compazine® and Benadryl®, hang the IV bag, and administer the contents of the vial. Therefore, every patient will receive a push of the contents in the vial (ketorolac or normal saline) and an 100mL infusion (Ofirmev or normal saline).

Official Title
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A Randomized Double-blind Comparative Efficacy Trial of IV Acetaminophen Versus IV Ketorolac for Emergency Department Treatment of Generalized Headache

Conditions
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Headache

Intervention / Treatment
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* Drug: Ketorolac
* Drug: Acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 65 years Presenting chief complaint of headache, migraine, tension headache, cluster headache, or headache not otherwise specified Report of pain 4 using a standard 11-point numerical scale (0 to 10; 0=no pain and 10=worst possible pain) Exclusion Criteria: Age < 18 years or > 65 years Inability to provide informed consent Physical or mental disability hindering adequate response to assessment of pain Hemodynamic instability/medical condition requiring acute life-saving medical intervention Documented or suspected pregnancy or currently breastfeeding Known brain mass, intracranial hemorrhage, skull fracture Known allergy, hypersensitivity, or prior adverse reaction to acetaminophen, NSAIDs, diphenhydramine, or prochlorperazine Known contraindications to acetaminophen use Severe hepatic impairment, severe active liver disease Known contraindications to ketorolac/NSAID use Active bleeding, peptic ulcer disease, bleeding dyscrasias Known contraindication to diphenhydramine use Known contraindication to prochlorperazine use Comatose states or in the presence of large amounts of CNS depressants Patients who have consumed > 2600 mg acetaminophen within the past 24 hours > 500 mg acetaminophen within the previous 4 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind trial comparing two parenteral adjuvant treatments for headache among patients presenting to the Lakeland Health Emergency Department in St. Joseph, MI.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketorolac Arm<br>The patient will receive a 0.9% normal saline bolus of 1,000ml at 500ml/hr, 25mg diphenhydramine IV, 10mg prochlorperazine IV, 15mg ketorolac in 100mL 0.9% normal saline IVPB | Drug: Ketorolac<br>* 15mg ketorolac in 100mL 0.9% normal saline IVPB 1,000mg acetaminophen in a 100ml IVPB<br>* Other names: Toradol;|
| Experimental: Acetaminophen Arm<br>The patient will receive a 0.9% normal saline bolus of 1,000ml at 500ml/hr, 25mg diphenhydramine IV, 10mg prochlorperazine IV, 1,000mg acetaminophen in a 100ml IVPB | Drug: Acetaminophen<br>* 1,000mg acetaminophen IVPB<br>* Other names: Ofirmev;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Improvement | Comparison of the improvement in pain score between baseline and 60 minutes following analgesic administration, assessed using a Numeric Pain Rating Scale ( RATE PAIN FROM 0-10, with 0 = no pain and 10 = worst possible pain) | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain score at 30 minutes | ED staff will re-assess the patient and record level of pain at time of study drug administration and at 30 minutes after study drug administration, pain assessed using a Numeric Pain Rating Scale ( RATE PAIN FROM 0-10, with 0 = no pain and 10 = worst possible pain) | 30 minutes | 
| pain score at 90 minutes | ED staff will re-assess the patient and record level of pain at time of study drug administration and at 90 minutes after study drug administration, pain assessed using a Numeric Pain Rating Scale ( RATE PAIN FROM 0-10, with 0 = no pain and 10 = worst possible pain) | 90 minutes | 
| need for rescue medication in the ED | ED staff will re-assess the patient and record level of pain at time of study drug administration and at 90 minutes after study drug administration, pain assessed using a Numeric Pain Rating Scale ( RATE PAIN FROM 0-10, with 0 = no pain and 10 = worst possible pain) | 90 minutes | 
| patient's desire to receive the same medication again | prior to discharge the ED staff will ask the patient if they would like to receive the same medication again. | 90 minutes | 
| Need for rescue medication | If a rescue medication is required, the time, pain level, and type of medication given will be recorded. pain assessed using a Numeric Pain Rating Scale ( RATE PAIN FROM 0-10, with 0 = no pain and 10 = worst possible pain) | 90 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acetaminophen, ketorolac, prochlorperazine, diphenhydramine