Clinical trial NCT02735343: The CHECK Trial: A Comparison of Headache Treatment in the Emergency Department: Compazine Versus Ketamine
Official title: The CHECK Trial: A Comparison of Headache Treatment in the Emergency Department: Compazine Versus Ketamine. A Multi-Center, Randomized, Double-Blind, Clinical Control Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Headache
Lead sponsor: Mike O'Callaghan Military Hospital
Sponsor class: FED
First posted: 2016-04-12
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigators are comparing Ketamine to prochlorperazinecompazine for benign headaches in the ED. Subjects will be randomized into 1 of 2 groups. Group 1 will receive standard treatment of prochlorperazinecompazine 10 mg IV along with diphenhydramine 25 mg IV. Group 2 (research arm) will receive Ketamine 0.3 mg/kg along with ondansetron 4 mg IV. Subjects will be seen at 15, 30, 45, and 60 minutes post-intervention to obtain Heart Rate, Blood Pressure, Headache severity, Nausea severity, Vomiting severity, Anxiety severity, and Restlessness severity. At 24-48 hours post intervention we will contact subjects and assess their pain and assess their satisfaction with their migraine pain management as part of this study. Subjects' participation will last up to 48 hours post headache.

Detailed description: Screening Visit:

* Obtain signed Informed Consent Document and HIPAA Authorization (research-driven).
* Record: Date of birth, age, phone number, gender, race, ethnicity, social security number, name of standard of care rescue medications (over-the-counter and prescription), current email address (to be used for scheduling only), height (in inches), weight (in pounds), history of traumatic brain injury, concussion, or any mild to severe head trauma, medication use. (research only)
* Review past medical history in Armed Forces Health Longitudinal Technology Application (AHLTA) or ESSENTRIS to verify the inclusion/exclusion criteria.
* Women of childbearing potential will have a serum pregnancy test (5-10 milliliters (mls), approximately 1-2 teaspoons of blood) (research-driven).

Visit 1:

* Heart rate
* Blood pressure
* Headache severity via 100-mm VAS.
* Nausea severity via 100-mm VAS.
* Vomiting severity via 100-mm VAS.
* Anxiety severity via 100-mm VAS.
* Restlessness severity via 100-mm VAS.
* Record type and amount of rescue medications (over-the-counter and prescription) use in the past 7 days. (research only)
* Subjects will be randomized by the pharmacy. We will use a random-number generator and use blocking to ensure roughly equal sample sizes. Both subjects and investigators will be blinded to the study group assignments. Subjects will be randomized by the pharmacy into one of two groups (research-driven):

  * Group 1: Standard treatment arm (prochlorperazinecompazine 10 mg IV along with diphenhydramine 25 mg IV)
  * Group 2: Research arm (Ketamine 0.3 mg/kg along with ondansetron 4 mg IV)

    15 minutes post treatment:
* Heart rate
* Blood pressure
* Headache severity via 100-mm VAS.
* Nausea severity via 100-mm VAS.
* Vomiting severity via 100-mm VAS.
* Anxiety severity via 100-mm VAS.
* Restlessness severity via 100-mm VAS.

  30 minutes post treatment:
* Heart rate
* Blood pressure
* Headache severity via 100-mm VAS.
* Nausea severity via 100-mm VAS.
* Vomiting severity via 100-mm VAS.
* Anxiety severity via 100-mm VAS.
* Restlessness severity via 100-mm VAS.

  45 minutes post treatment:
* Heart rate
* Blood pressure
* Headache severity via 100-mm VAS.
* Nausea severity via 100-mm VAS.
* Vomiting severity via 100-mm VAS.
* Anxiety severity via 100-mm VAS.
* Restlessness severity via 100-mm VAS.

  60 minutes post treatment:
* Heart rate
* Blood pressure
* Headache severity via 100-mm VAS.
* Nausea severity via 100-mm VAS.
* Vomiting severity via 100-mm VAS.
* Anxiety severity via 100-mm VAS.
* Restlessness severity via 100-mm VAS.

24-48 hours post treatment:

* Subjects will be contacted either in-person or via phone and the following information will be collected:

  * Subjects will be asked "On a scale of 0-10, with 10 being the worst pain, what is your current level of pain?"
  * Subjects will be asked "On a scale of 0 to 10, how satisfied were you with you're the migraine pain management as part of this research study? (dissatisfied 0 - 10 very satisfied)
* Subjects will be alerted to what group they were randomized into.

Eligibility criteria: THIS STUDY IS BEING CONDUCTED AT A MILITARY INSTALLATION. YOU MUST HAVE MILITARY INSURANCE IN ORDER TO PARTICIPATE IN THIS STUDY.

Inclusion Criteria

* Age 18 to 65 years who present to the ED with complaint of a headache
* Temperature less than 100.4 F
* Diastolic blood pressure less than 104 mm Hg
* Normal neurologic exam and normal mental status

Exclusion Criteria

* Pregnant or breastfeeding
* Meningeal signs are present
* Acute angle closure glaucoma is suspected
* Head trauma within the previous two weeks
* Lumbar puncture within the previous two weeks
* Thunderclap (rapid) onset of the headache
* Weight more than 150 kg or less than 40 kg
* Known allergy to diphenhydramine
* Known allergy to ondansetron. (Zofran)
* Known allergy to Compazine
* Known allergy to Ketamine
* History of schizophrenia or bipolar disorder
* History of intracranial hypertension
* Is a prisoner
* Patient declined informed consent
* Non-English speaking patient
* Attending provider excludes patient
* Elderly patients with dementia
* Patients with severe headaches that diminish their decision making capability will not be able to participate

Primary outcomes:
measure: Pain Score
timeFrame: 15 min, 30 min, 45 min, 60 min
Secondary outcomes:
Other outcomes:
Locations:
city: Nellis Air Force Base
country: United States
facility: Mike O'Callaghan Federal Medical Center
state: Nevada
Study officials:
affiliation: Mike O'Callaghan Federal Medical Center
name: Christopher Pitotti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Driver BE, Klein LR, Carlson K, Harrington J, Reardon RF, Prekker ME. Preoxygenation With Flush Rate Oxygen: Comparing the Nonrebreather Mask With the Bag-Valve Mask. Ann Emerg Med. 2018 Mar;71(3):381-386. doi: 10.1016/j.annemergmed.2017.09.017. Epub 2017 Oct 28.
citation: Zitek T, Gates M, Pitotti C, Bartlett A, Patel J, Rahbar A, Forred W, Sontgerath JS, Clark JM. A Comparison of Headache Treatment in the Emergency Department: Prochlorperazine Versus Ketamine. Ann Emerg Med. 2018 Mar;71(3):369-377.e1. doi: 10.1016/j.annemergmed.2017.08.063. Epub 2017 Oct 14.