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

Headache Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03472872
• Other study ID #: MMMC#1569
• Status: Withdrawn
• Phase: Phase 4
• Start date: September 5, 2017
• Est. completion date: June 14, 2020

Study information

• Verified date: May 2024
• Source: Spectrum Health - Lakeland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 14, 2020
• Est. primary completion date: June 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Emergencies
• Headache

Intervention

Drug:
• Ketorolac
15mg ketorolac in 100mL 0.9% normal saline IVPB 1,000mg acetaminophen in a 100ml IVPB
• Acetaminophen
1,000mg acetaminophen IVPB

Locations

Country	Name	City	State
United States	Lakeland Regional Healthcare	Saint Joseph	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Spectrum Health - Lakeland	Michigan State University

Country where clinical trial is conducted

United States, 

References & Publications (21)

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Florence CS, Zhou C, Luo F, Xu L. The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013. Med Care. 2016 Oct;54(10):901-6. doi: 10.1097/MLR.0000000000000625. — View Citation

Friedman BW, Adewunmi V, Campbell C, Solorzano C, Esses D, Bijur PE, Gallagher EJ. A randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches. Ann Emerg Med. 2013 Oct;62(4):311-318.e4. doi: 10.1016/j.annemergmed.2013.03.017. Epub 2013 Apr 6. — View Citation

Friedman BW, Cabral L, Adewunmi V, Solorzano C, Esses D, Bijur PE, Gallagher EJ. Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial. Ann Emerg Med. 2016 Jan;67(1):32-39.e3. doi: 10.1016/j.annemergmed.2015.07.495. Epub 2015 Aug 29. — View Citation

Friedman BW, Esses D, Solorzano C, Dua N, Greenwald P, Radulescu R, Chang E, Hochberg M, Campbell C, Aghera A, Valentin T, Paternoster J, Bijur P, Lipton RB, Gallagher EJ. A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Ann Emerg Med. 2008 Oct;52(4):399-406. doi: 10.1016/j.annemergmed.2007.09.027. Epub 2007 Nov 19. — View Citation

Friedman BW, West J, Vinson DR, Minen MT, Restivo A, Gallagher EJ. Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015 Apr;35(4):301-9. doi: 10.1177/0333102414539055. Epub 2014 Jun 19. — View Citation

Gungor F, Akyol KC, Kesapli M, Celik A, Karaca A, Bozdemir MN, Eken C. Intravenous dexketoprofen vs placebo for migraine attack in the emergency department: A randomized, placebo-controlled trial. Cephalalgia. 2016 Feb;36(2):179-84. doi: 10.1177/0333102415584604. Epub 2015 May 5. — View Citation

Jones J, Sklar D, Dougherty J, White W. Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache. JAMA. 1989 Feb 24;261(8):1174-6. — View Citation

Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M. Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study. Arch Intern Med. 2000 Dec 11-25;160(22):3486-92. doi: 10.1001/archinte.160.22.3486. — View Citation

Lucado J, Paez K, Elixhauser A. Headaches in U.S. Hospitals and Emergency Departments, 2008. 2011 May. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #111. Available from http://www.ncbi.nlm.nih.gov/books/NBK56047/ — View Citation

Masoumi K, Forouzan A, Asgari Darian A, Feli M, Barzegari H, Khavanin A. Comparison of clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic: a randomized, double-blind, controlled trial. Emerg Med Int. 2014;2014:571326. doi: 10.1155/2014/571326. Epub 2014 Aug 13. — View Citation

Needleman SM. Safety of rapid intravenous of infusion acetaminophen. Proc (Bayl Univ Med Cent). 2013 Jul;26(3):235-8. doi: 10.1080/08998280.2013.11928969. — View Citation

Orr SL, Friedman BW, Christie S, Minen MT, Bamford C, Kelley NE, Tepper D. Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2016 Jun;56(6):911-40. doi: 10.1111/head.12835. — View Citation

Pardutz A, Schoenen J. NSAIDs in the Acute Treatment of Migraine: A Review of Clinical and Experimental Data. Pharmaceuticals (Basel). 2010 Jun 17;3(6):1966-1987. doi: 10.3390/ph3061966. — View Citation

Shrestha M, Singh R, Moreden J, Hayes JE. Ketorolac vs chlorpromazine in the treatment of acute migraine without aura. A prospective, randomized, double-blind trial. Arch Intern Med. 1996 Aug 12-26;156(15):1725-8. — View Citation

Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH. Ketorolac in the treatment of acute migraine: a systematic review. Headache. 2013 Feb;53(2):277-87. doi: 10.1111/head.12009. Epub 2013 Jan 8. — View Citation

Turkcuer I, Serinken M, Eken C, Yilmaz A, Akdag O, Uyan E, Kiray C, Elicabuk H. Intravenous paracetamol versus dexketoprofen in acute migraine attack in the emergency department: a randomised clinical trial. Emerg Med J. 2014 Mar;31(3):182-5. doi: 10.1136/emermed-2013-203044. Epub 2014 Jan 6. — View Citation

Vinson DR, Drotts DL. Diphenhydramine for the prevention of akathisia induced by prochlorperazine: a randomized, controlled trial. Ann Emerg Med. 2001 Feb;37(2):125-31. doi: 10.1067/mem.2001.113032. — View Citation

Vinson DR, Hurtado TR, Vandenberg JT, Banwart L. Variations among emergency departments in the treatment of benign headache. Ann Emerg Med. 2003 Jan;41(1):90-7. doi: 10.1067/mem.2003.24. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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