Acute Migraine Treatment in the ED With Gepants

• Rimegepant (Drug): Rimegepant 75 mg orally disintegrating tablet (ODT), administered as a single dose
• Zavegepant (Drug): Zavegepant 10 mg nasal spray, administered as a single dose

Primary outcomes

• Percentage of participants with pain relief at 2 hours without rescue medication [120 minutes (2 hours)]: Percentage of participants reporting pain as 'mild' or 'none' at 2 hours post-study drug administration, without rescue medication. Pain is categorized as none, mild, moderate, or severe.

Secondary outcomes

• Percentage of participants with pain relief at 2 hours post treatment [120 minutes (2 hours) post treatment]: Effectiveness of treatment measured as percentage of participants with pain relief achieving "mild" or "none" at 2 hours post-study drug administration. Pain is categorized as none, mild, moderate, or severe.
• Percentage of participants with pain relief at 60 minutes post treatment [60 minutes post treatment]: Effectiveness of treatment measured as percentage of participants with pain relief achieving "mild" or "none" at 60 minutes post-study drug administration. Pain is categorized as none, mild, moderate, or severe.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* At least 18 years of age
* Capacity to provide informed consent (without a Legally Authorized Representative)
* Prior migraine diagnosis (clinical or self-reported)
* Emergency Department presentation for a headache fulfilling International Classification of Headache Disorders (ICHD-3) criteria for migraine with typical aura or without aura, or criteria for probable migraine with typical aura or without aura. Duration of migraines should be ≥ 1 year. It is acceptable if current headache duration is >72 hours. Must have been headache free for >48 hours prior to current attack.
* Willingness to participate in post-discharge telephone or electronic follow-up assessments

Exclusion Criteria:

* Suspected secondary headache due to another cause, or primary headache disorder other than migraine or probable migraine
* Prior healthcare encounter for headache within 7 days
* Use of analgesics or abortive headache medications within 2 hours of consent
* Use of intranasal decongestant within 12 hours of consent
* Use of the following drug/food categories with potential for drug interactions within 7 days or 5 half-lives, whichever is longer: 1) CYP3A strong or moderate inducers, 2) CYP3A4 strong inhibitors, 3) P-glycoprotein (P-gp) inhibitors, 4) OATP1B3 transporter potent inhibitors/inducers, 5) NTCP transporter potent inhibitors/inducers
* History of cardiovascular disease, hypertension, or diabetes, recently diagnosed or currently uncontrolled or unstable
* History of stroke, peripheral vascular disease, or medically-diagnosed Raynaud's Phenomenon
* History of severe hepatic impairment, as assessed by the investigator or qualified delegate
* History of kidney disease stage 4 (creatinine clearance <30 mL/min or eGFR <35 mL/min/1.73 m2)
* History of nasal condition that may affect zavegepant administration, as assessed by the investigator or qualified delegate
* History of hypersensitivity reaction to rimegepant, zavegepant, or to any included inactive ingredients
* Lifetime use of CGRP-targeting acute or preventive migraine medications
* In custody of law enforcement
* Current pregnancy or lactation

• Jonathan Schimmel, Principal investigator, Icahn School of Medicine at Mount Sinai