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Comparing atogepant, topiramate, and propranolol for migraine prevention

A Comparative Effectiveness Study of Oral Medications Used for Migraine Prevention: The APT Comparison Study

Phase 4 Interventional Mayo Clinic · NCT06972056

This trial will test whether the newer drug atogepant works better and causes fewer side effects than topiramate or propranolol for adults with migraine who have at least four moderate-to-severe headache days per month.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment1335 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorMayo Clinic Academic / other
Locations23 sites (Flagstaff, Arizona and 22 other locations)
Trial IDNCT06972056 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, comparative effectiveness trial that assigns adults with migraine to atogepant, propranolol, or topiramate after a four-week run-in headache diary. Eligible participants complete a daily headache diary for four weeks, then are randomized to one of the three medications and treated for twelve weeks with follow-up visits through 48 weeks. The primary outcome is the proportion of participants who complete twelve weeks on their assigned medication and achieve a 50% or greater reduction in moderate-to-severe headache days during weeks 9–12 compared with the four-week pre-randomization period. Doses include atogepant 60 mg, propranolol 160 mg, and topiramate 100 mg, with visits at baseline, randomization (week 4), and weeks 4, 8, 12, 24, and 48 post-randomization.

Who should consider this trial

Good fit: Adults 18–70 with migraine (with or without aura, including chronic migraine) for at least 12 months who report at least four moderate-to-severe headache days per month and can complete a 4-week diary and attend scheduled clinic visits are ideal candidates.

Not a fit: People who are pregnant or breastfeeding, cannot commit to the diary and visit schedule, or who have migraine onset after age 50 may not benefit or be eligible for this trial.

Why it matters

Potential benefit: If successful, the trial could identify which medication provides better migraine reduction and tolerability, helping clinicians choose a more effective preventive option.

How similar studies have performed: Previous randomized trials have shown that atogepant is effective for migraine prevention and topiramate and propranolol are established preventives, but direct head-to-head comparisons like this are limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Adults, 18-70 years of age at the time of enrollment
* Migraine with aura, migraine without aura, and/or chronic migraine; according to ICHD-3 diagnostic criteria. (Those with daily or continuous headaches are not excluded.)
* Migraine onset prior to 50 years of age
* Migraine present for at least 12 months at the time of enrollment
* At least four "moderate to severe headache days" per month (by patient self-report and then confirmed during four-week pre-randomization headache diary phase) A "moderate to severe headache day" is defined as a day during which there is a headache of moderate to severe intensity that lasts for at least four hours, or a day on which a migraine-specific acute medication is taken to treat headache.
* If already taking a migraine preventive treatment, willing to continue with that treatment without dose change during the first 16 weeks of the study, including the 4-week run-in phase and 12-week randomized phase.
* Not pregnant or breastfeeding
* Women of childbearing potential must agree to use effective methods of contraception to reduce the risk of pregnancy.
* Willingness and ability to provide informed consent.
* Willingness and ability to complete all research visits.

Exclusion Criteria:

* Contraindications to taking atogepant, propranolol, or topiramate.
* Currently taking atogepant, propranolol, or topiramate\*
* Previously took atogepant, propranolol, or topiramate\*
* Unwillingness to take atogepant, topiramate, or propranolol.
* Current use of a CGRP-targeting preventive medication or beta-blocker
* Migraine with brainstem aura
* Hemiplegic migraine
* Retinal migraine
* Migraine aura without headache (exclusively)
* Pure menstrual migraine
* Trigeminal autonomic cephalalgias
* Facial neuralgias
* Secondary headache disorders (medication overuse headache is not an exclusion)
* Migraine preventive treatment has been started or dose has been changed within 12 weeks prior to potential enrollment.
* Used opioids or butalbital on five or more days per month on average for at least 3 months prior to enrollment.
* Current or past epilepsy
* Severe hepatic impairment
* Moderate or more severe renal impairment \* Occasional as needed use of propranolol, currently or in the past, is not an exclusion, such as taking as needed propranolol for treatment of anxiety.

Where this trial is running

Flagstaff, Arizona and 22 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions MigraineMigraine with auraMigraine prevention
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.