An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin in Treatment of Acute Headache

• ClinicalTrials.gov Identifier: NCT04860713
• Recruitment Status: Recruiting
• First Posted: April 27, 2021
• Last Update Posted: February 17, 2022
• Sponsor: Antonios Likourezos
• Information provided by (Responsible Party): Antonios Likourezos, Maimonides Medical Center

Tracking Information

• First Submitted Date: April 22, 2021
• First Posted Date: April 27, 2021
• Last Update Posted Date: February 17, 2022
• Actual Study Start Date: April 22, 2021
• Estimated Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 26, 2021)

Change in Pain score at 60 minutes [ Time Frame: 60 minutes ]

Change of pain scores on numeric rating pain scale (NRS) at 60 minutes mark form the baseline. The NRS is an 11 item Likert Scale ranging from 0 (no pain) to 10 (very severe pain) with 5 indicating moderate pain.

Original Primary Outcome Measures (submitted: April 26, 2021)

Reduction in Pain score at 60 minutes [ Time Frame: 60 minutes ]

Reduction of pain scores on numeric rating pain scale (NRS) at 60 minutes mark form the baseline. The NRS is an 11 item Likert Scale ranging from 0 (no pain) to 10 (very severe pain) with 5 indicating moderate pain.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin in Treatment of Acute Headache
• Official Title: An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin and Nurtec (Rimegepant) in Adult Patients Presenting to the ED With Acute Headache: Prospective, Randomized, Open-Label, Clinical Trial
• Brief 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).

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pain

Intervention

• Drug: aspirin and ketamine
  Drug: Proprietary oral formulation of 0.85mg/kg of ketamine + 324mg of aspirin
• Drug: Nurtec (Rimegepant)
  Drug: 75 mg of ODT

Study Arms

• Active Comparator: AOK Group
  Drug: Proprietary oral formulation of 0.85mg/kg of ketamine + 324mg of aspirin
  Intervention: Drug: aspirin and ketamine
• Active Comparator: Nurtec (Rimegepant) Group
  Drug: 75 mg of ODT
  Intervention: Drug: Nurtec (Rimegepant)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 26, 2021): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients age 18 and older
• Acute Headache
• Initial pain score of 5 or more on a standard 11- point (0 to 10) numeric rating scale.
• Awake, alert, and oriented to person, place, and time

Exclusion Criteria:

• altered mental status,
• allergy to aspirin, ketamine and rimegepant,
• pregnancy and breastfeeding
• unstable vital signs (systolic blood pressure <90 or>180 mm Hg, pulse rate <50 or >150 beats/ min, and respiration rate <10 or >30 breaths/min)
• inability to provide consent
• consumption of Aspirin or NSAID's within 6 hours of arrival to the ED or acetaminophen within 4 hours of arrival
• active PUD
• history of GI Hemorrhage
• history of renal and hepatic insufficiency
• past medical history of alcohol or drug abuse
• schizophrenia
• clinical findings concerning for acute intracranial process, acute infections process

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Antonios Likourezos, MA, MPH; 7182836896; alikourezos@maimonidesmed.org

Contact: Leily Naraghi, MD; LNaraghi@maimonidesmed.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04860713
• Other Study ID Numbers: 2021-02-03-MMC
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Antonios Likourezos, Maimonides Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Antonios Likourezos
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Leily Naraghi, MD; Maimonides Medical Center

• PRS Account: Maimonides Medical Center
• Verification Date: February 2022