Ketamine v. Ketorolac for Management of Generalized Tension Type Headache

The hypothesis of the study is that sub-dissociative dose ketamine will prove to be superior to or as standard therapy, ketorolac, in the treatment of acute tension type headache (TTH) as measured by the 10 point Numerical Rating Scale (NRS. The aim of the study is to compare the safety & efficacy of intravenous sub-dissociative dose ketamine versus ketorolac for acute treatment of migraines in the Emergency Department (ED) The primary endpoints are: Patient perception of pain as described by the use the Numerical Rating Scale (NRS) at 30 minutes.

The secondary endpoints are: Frequency and mean dose of rescue/additional doses of therapy at 15, 30, 45, 60, 75, 90 min, Number of emergency department re-visits for acute migraine one month post discharge, incidence of dissociative effects (characterized by hallucination, disorientation, confusion, agitation, delirium, dreams) during study period, incidence of nausea, vomiting, or worsening headache, Incidence of bad taste, Incidence of burning sensations in the nostrils, incidence of hypertension, time to patient discharge from the initiation of study medication/placebo, patient satisfaction of pain control based on a Likert Scale.

Study Overview

• Status: Unknown
• Conditions: Migraine
• Intervention / Treatment: Drug: Intravenous ketamine; Drug: Normal saline; Drug: Normal saline; Drug: Ketorolac

Detailed Description

This will be a "double-dummy" study in that there will be no placebo only arm. Medications will be administered in a double blind randomized fashion. Patients would be enrolled in Arm A or Arm B depending upon the initial randomization. Arm A would include 0.3 mg/kg ketamine into a 100 cc normal saline IV bag and normal saline injection (1ml) while Arm B would receive 100cc of normal saline and 30mg of ketorolac intravenously.

An order would be placed by the medical resident, medical attending, a study investigator who is a physician, or a pharmacist under the permission of the attending physician into Allscripts for a study intervention. Upon receiving the order in Allscripts, the order would be verified by the pharmacy. All medications will be prepared in pharmacy, which will maintain a master list of contents of each sealed envelope. Once notified of which envelope has been pulled, the pharmacist will prepare either arm. ED personnel will obtain the infusion preparation from pharmacy. It will be labeled for the patient, with study number, but without other identifying marks. When the study medication is picked up, pharmacy will open the sealed envelope to confirm which medication arm was prepared in order to internally verify the correct preparation. The nurse assigned to the patient would administer the intervention. A research associate or a study investigator would approach the patient to assess and record primary outcomes, secondary outcomes at designed time intervals. The data will be recorded on the data collection instrument. If additional medication is requested by the patient, the orders would be placed by the medical resident or attending who are assigned to the patient in the ED. Upon completion of the treatment portion of the study, patients will be asked of the participant's satisfaction with therapy. Only the patient who signed the consent form will be allowed to answer the questions.

All data retrieved from the paper data collection sheets will be transcribed into an encrypted and password protected electronic database by the research associate. All patient identifiers would be de-identified in the database. All participants would be assigned a study participant number.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Billy Sin, PharmD; Phone Number: 2450 718-250-5000; Email: bsin@tbh.org

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11201
      • Recruiting
      • The Brooklyn Hospital Center
      • Contact: Billy W Sin, Pharm.D.; Phone Number: 718-250-6250

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The inclusion criteria are: Patients 18-65 years old who provides informed consent and presents to the ED with an acute tension type headache (TTH), as classified by meeting the following:

  1. Have at least 10 episodes of headache occurring on average less than 12 days per year AND Fullfuling B-D B. Lasting 30mins to 7 days C. At least 2 of the following 4 criteria
  1. bilateral location
  2. pressing/tightening (non-pulsating)
  3. mild or moderate
  4. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following
  1. no nausea/vomiting
  2. No more than one of photophobia or phonophobia

Exclusion Criteria: Non migraine primary headache disorder or unclassifiable, previous enrollment in study, fever >100.3, Patients with suspected secondary headache disorder such as SAH or sinusitis, performance of lumbar puncture or potential need for LP, Severe hypertension (≥180/100), History of CAD or hypertension, presence of/suspected for traumatic head injury in the past 30 days with or without loss of consciousness, Presence of/suspected for myocardial ischemia, presence of/suspected for alcohol intoxication, Hemodynamic instability, history of psychiatric disorders, known or suspected pregnancy or breast feeding, allergy to ketamine, ketorolac, previous enrollment in the study, patients with language barriers, refusal to provide consent to receive intravenous therapy, reported illicit drug use within the past 5 days, patients weighing over 100kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous ketamine; Arm will include 0.3 mg/kg intravenous piggyback ketamine over 10 minutes for 1 dose and a 1ml normal saline placebo via intravenous push	Drug: Intravenous ketamine; 0.3mg/kg IVPB over 15 minutes; Other Names: ketamine intravenous; Drug: Normal saline; Will be given as 50ml intravenous bag as placebo for double-blinding purposes in patients who will also receive intranasal ketamine. Will be prepared in intranasal syringe for double blinding purposes for patients who are randomized to receive intranasal ketamine.; Other Names: saline; Drug: Normal saline; 1ml intravenous push as placebo for double-blinding purposes; Other Names: saline
Active Comparator: ketorolac; Arm will include 30mg ketorolac intravenous push and 50ml normal saline over 10 minutes	Drug: Normal saline; Will be given as 50ml intravenous bag as placebo for double-blinding purposes in patients who will also receive intranasal ketamine. Will be prepared in intranasal syringe for double blinding purposes for patients who are randomized to receive intranasal ketamine.; Other Names: saline; Drug: Normal saline; 1ml intravenous push as placebo for double-blinding purposes; Other Names: saline; Drug: Ketorolac; as active comparator, will be administered together with metoclopramide in one normal saline 50ml bag

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores	10 point number rating scale	At 30 minutes after initiation of study intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	adverse events reported in each group	throughout study period (105 mins)
mean dose of rescue analgesia required	dose of rescue analgesia required in each group	throughout study period (105 minutess)
length of stay	median ED length of stay in each group	throughout study period (105 minutes)

Collaborators and Investigators

• Sponsor: The Brooklyn Hospital Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 6, 2018
• Last Update Submitted That Met QC Criteria: July 5, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Headache; Tension-Type Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketamine; Ketorolac
• Other Study ID Numbers: 779354-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No