An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin in Treatment of Acute Headache
Condition: Pain
MeSH terms: Headache
Study type: Interventional
Phase: Phase 4

Summary: 
      Headaches affect over 50% of patients annually, with close to 4% of ED visits for headache.
      Most headaches managed in the ED are benign, with 90% of these headaches classified as
      tension, migraine, or cluster. At present, the satisfaction with ED treatment of headache is
      low, and despite the multitude of available medications, the evidence- based treatment
      options are often quite limited. There are over twenty different types of medications
      available to the ED clinicians for managing headache, many with different routes of
      administration (parenteral, intranasal, subcutaneous, and oral). Many of these medications
      are provided in so-called "headache cocktail", which varies based on the physician,
      institution, and patient preferences.
    

Detailed description: 
      STUDY OBJECTIVES: To compare analgesic efficacy and rates of side effects of a proprietary
      formulation of orally administered aspirin and ketamine (AOK) to a Nurtec ODT (Rimegepant)
      for pain management in adult ED patients presenting to the ED with acute headache.

      HYPOTHESIS: We hypothesize that the administration of AOK will provide similar analgesia at
      60 minutes post-administration in comparison to Nurtec (Rimegepant) in adult patients
      presenting to the ED with acute headache. The primary outcome of this trial is the difference
      in participant's pain scores at 60 minutes post-medication administration.

      STUDY DESIGN:

      Subjects:

      Patients 18 years of age and older presenting to the ED with acute headache (defined as HA
      lasting no more than 1 week) and an initial pain score of 5 or more on a standard 11- point
      (0 to 10) numeric rating scale and requiring oral analgesia as determined by the treating
      attending physician. Patients' screening and enrollment will be performed by study
      investigators and research assistants. All patients will be enrolled at various times of the
      day when study investigators will be available for patient enrollment and an ED pharmacist
      will be available for medication preparation.

      Design: This is a prospective, randomized, open-label, equivalence trial comparing analgesic
      efficacy and safety of AOK and Nurtec (Rimegepant) in patients presenting to the ED of
      Maimonides Medical Center with acute headache. Upon meeting the eligibility criteria,
      patients will be randomized into one of the two study arms: Group I will receive AOK, and
      Group II will receive Nurtec.

      Data Collection Procedures: Each patient will be approached by a study investigator for
      acquisition of written informed consent and Health Insurance Portability and Accountability
      Act authorization after being evaluated by the treating emergency physician and determined to
      meet study eligibility criteria. When English will not be the participant's primary language,
      a language- appropriate consent form will be used and non-investigator, hospital employed,
      trained interpreters or licensed telephone interpreters will assist in acquisition of
      informed consent. Baseline pain score will be determined with an 11-point numeric rating
      scale (0 to 10), described to the patient as "no pain" being 0 and "the worst pain
      imaginable" being 10. A study investigator will record the patient's body weight and baseline
      vital signs. All data will be recorded on data collection sheets, including patients' sex,
      demographics, medical history, and vital signs, and entered into SPSS (version 24.0; IBM
      Corp) by the research manager. Confirmation of written consent acquisition for all
      participants, and statistical analyses will be conducted by the statistician, who will work
      independently of any data collection.

      Expected Outcomes: The primary outcome will include a comparative reduction of pain scores on
      numeric rating pain scale (NRS) at 60 minutes from the baseline. The secondary outcomes will
      include a need for rescue analgesia, rates of adverse effects and change in pain score up to
      120 minutes. With respect to unique adverse effects of ketamine, we will use Side Effect
      Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation Sedation Scale
      (RASS) (ref) SERSDA Scale includes fatigue, dizziness, nausea, headache, feeling of
      unreality, changes in hearing, mood change, general discomfort, and hallucinations with
      severity of each graded by patients on a five-point scale, with "0" representing the absence
      of any adverse effects and "4" representing a severely bothersome side effect. RASS evaluates
      the severity of agitation and/or sedation in accordance with the nine-point scale with scores
      ranging from "-4" (deeply sedated) to "0" (alert and calm) to "+4" (combative).
    

Intervention name(s): aspirin and ketamine; Nurtec (Rimegepant)
Intervention type(s): Drug; Drug
Intervention description(s): Drug: Proprietary oral formulation of 0.85mg/kg of ketamine + 324mg of aspirin; Drug: 75 mg of ODT
Intervention MeSH terms: Aspirin; Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Emergency Medicine; Pain; Pain Management; Acute Headache