Treatments of Migraine with Triptans in Individuals with Elevated Cardiovascular Risk and in Pregnant Women

Researchers are evaluating the safety of triptan treatment of migraine in individuals with elevated cardiovascular risk and in pregnant women.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Migraine; Pregnancy
• Intervention / Treatment: Drug: Acute migraine treatment with any prescribed triptans; Drug: Standard of care management of acute migraine without triptans

Detailed Description

Migraine is a very common condition that can be associated with significant morbidity. For the acute treatment of migraine attacks, the use of triptans, NSAIDs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments are associated with improved pain and function. The effectiveness of these therapies has been documented in various studies and summarized in systematic reviews. However, systematic reviews have demonstrated evidence gaps in two groups of patients that were excluded from treatment trials. These are patients with cardiovascular disease or at high risk of cardiovascular events, and pregnant women.

Triptans, the mainstay treatment for migraine attacks and the one supported by the highest quality evidence, are considered vasoactive and are contraindicated per formulary in individuals who have a history of myocardial infarction, stroke, or uncontrolled vascular risk factors such as hypertension. These individuals are usually excluded from randomized trials. Similarly, pregnant women have been excluded from triptans trials and the observational studies offered low certainty evidence about their safety. Yet, 44% of surveyed members of the American Headache Society reported being somewhat or very comfortable using triptans in pregnancy.

Therefore, the investigators intend to evaluate the safety of triptan treatment of migraine in individuals with cardiovascular disease or multiple cardiovascular risk factors, and in pregnant women in two target trial emulations.

• Study Type: Observational
• Enrollment (Actual): 68419

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients were identified through Mayo Clinic electronic health records.

Description

Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk:

Inclusion:

• Aged >=18 years
• At least 1 year history of migraine with or without aura
• Confirmed cardiovascular or cerebrovascular disease, including myocardial infarction (MI), coronary artery disease (CAD), cerebrovascular disease, stroke; or at least 2 cardiovascular risk factors, including diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, peripheral vascular disease;
• At least 1 year of prior triptan treatment or no previous triptan treatment.

Exclusion:

• Prescription of ergot alkaloids or dihydroergotamine within 60 days before or after starting treatment

Treatments of Migraine With Triptans in Pregnant Women

Inclusion:

• Aged >=18 years
• Pregnant woman
• Diagnosis of episodic or chronic migraine with or without aura before pregnancy

Exclusion:

• Prescription of ergot alkaloids or dihydroergotamine <= 60 days before pregnancy or during pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cardiovascular Risk Group Treated with Triptans; Subjects with diagnosis of migraine and cardiovascular disease, cerebrovascular disease and/or two or more cardiovascular risk factors who received Triptans as part of clinical care.	Drug: Acute migraine treatment with any prescribed triptans; Sumatriptan, treximet (sumatriptan/naproxen combination), zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. No restriction on dose, frequency, duration, or delivery routes.; Other Names: Triptans
Cardiovascular Risk Control Group Treated with No Triptans; Subjects with who did not received Triptans as part of clinical care.	Drug: Standard of care management of acute migraine without triptans; Any standard of care management without triptans; Other Names: No triptans
Pregnant Women Group Treated with Triptans; Subjects diagnosed with migraine that received Triptans as part of clinical care during pregnancy.	Drug: Acute migraine treatment with any prescribed triptans; Sumatriptan, treximet (sumatriptan/naproxen combination), zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. No restriction on dose, frequency, duration, or delivery routes.; Other Names: Triptans
Pregnant Women Control Group Treated with No Triptans; Subjects that did not receive Triptans as part of clinical care during pregnancy.	Drug: Standard of care management of acute migraine without triptans; Any standard of care management without triptans; Other Names: No triptans

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events (MACE)	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: number of subjects to experience major adverse cardiovascular events (MACE) which consists of all-cause death, nonfatal myocardial infarction, nonfatal stroke, heart failure, transient cerebral ischemia, or revascularization	60 days of starting treatment
Full term birth	Treatments of Migraine With Triptans in Pregnant Women: number of pregnant women to have a full term birth	39 0/7 weeks of gestation through 40 6/7 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all-cause death	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: all-cause death	60 days of starting treatment
Nonfatal myocardial infarction	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: nonfatal myocardial infarction	60 days of starting treatment
Nonfatal stroke	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: nonfatal stroke	60 days of starting treatment
Heart failure	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: Heart failure	60 days of starting treatment
Transient cerebral ischemia	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: transient cerebral ischemia	60 days of starting treatment
Revascularization	Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: revascularization	60 days of starting treatment
Pre-term delivery	Treatments of Migraine With Triptans in Pregnant Women: Pre-term delivery	37 0/7 weeks of gestation through 38 6/7 weeks of gestation
Cesarean section delivery	Treatments of Migraine With Triptans in Pregnant Women: cesarean section delivery	up to delivery
Spontaneous abortions/miscarriage	Treatments of Migraine With Triptans in Pregnant Women: Spontaneous abortions/miscarriage	up to delivery
Fetal death/stillbirth	Treatments of Migraine With Triptans in Pregnant Women: Fetal death/stillbirth	up to delivery
Intra-uterine growth restriction	Treatments of Migraine With Triptans in Pregnant Women: Intra-uterine growth restriction	up to delivery
Eclampsia/preeclampsia	Treatments of Migraine With Triptans in Pregnant Women: Eclampsia/preeclampsia	up to delivery
Tubal or ectopic pregnancy	Treatments of Migraine With Triptans in Pregnant Women: Tubal or ectopic pregnancy	up to delivery
Major fetal malformations	Treatments of Migraine With Triptans in Pregnant Women: Major fetal malformations	up to delivery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Agency for Healthcare Research and Quality (AHRQ)
• Investigators: Principal Investigator: Mohammad Murad, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): November 1, 2024
• Study Completion (Actual): November 1, 2024

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Estimated): December 2, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Cardiovascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Serotonin Receptor Agonists; Serotonin 5-HT1 Receptor Agonists
• Other Study ID Numbers: 22-005920

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No