Comparison of the Effectiveness of First-line Preventive Treatment of Migraine in Primary Care

NCT06499116 | Not Yet Recruiting Phase 4

• 2 other identifiers: IJG-PREMI-20242024-513597-22-00
• Study Type: interventional
• Target: 460
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study, which is aimed at comparing the effectiveness of the most frequently used drugs in the first line in primary care for the preventive treatment of migraine (amitriptyline, flunarizine, topiramate and propranolol), is a multicentre, pragmatic, parallel group, open randomised trial. Adults (≥18) candidates for preventive treatment for migraine; those with a frequency of ≥4 monthly migraine days, and who agree to participate in the clinical trial, will be randomised to one of the 4 groups. Sample: 460 patients. The primary outcome will be the reduction in monthly migraine days, comparing amitriptyline, flunarizine and topiramate with propranolol.

Conditions

Migraine

Keywords

Migraine; Monthly Migraine Days (MMD); Preventive treatment; Primary care

Outcome Measures

Primary Outcomes (1)

• To evaluate the effectiveness of the most frequently used drugs in primary care for the preventive treatment of migraine according to the reduction in monthly migraine days, comparing amitriptyline, flunarizine and topiramate with propranolol.

  Clinical effectiveness: change in the mean number of monthly migraine days (MMD) at 12 weeks of treatment from baseline.

  12 weeks

Secondary Outcomes (11)

• Calculate the rate of responders (reduction of at least 50% in monthly migraine days compared to baseline)

  12 weeks

• Evaluate effectiveness before completing the clinical trial

  4, 8 and 12 weeks

• Estimate the reduction in the intensity of migraine attacks

  4, 8 and 12 weeks

• Estimate the prevalence of symptoms associated with migraine

  12 weeks

• Evaluate adherence to preventive treatment

  12 weeks

Study Arms (4)

Topiramate

EXPERIMENTAL

25-100 mg/12h, V.O., during 12 weeks

Drug: Topiramate

Flunarizine

EXPERIMENTAL

2,5-10 mg/24h, V.O., during 12 weeks

Drug: Flunarizine

Amitriptyline

EXPERIMENTAL

10-75 mg/24h, V.O., during 12 weeks

Drug: Amitriptyline

Propranolol

ACTIVE COMPARATOR

20-120 mg/12h, V.O., during 12 weeks

Drug: Propranolol

Interventions

Topiramate DRUG

Treatment will be prescribed for GPs and they will decide the specific dosage 25-100 mg/12h.

Also known as: Acomicil

Topiramate

Flunarizine DRUG

Treatment will be prescribed for GPs and they will decide the specific dosage 2,5-10 mg mg/24h.

Also known as: Sibelium

Flunarizine

Amitriptyline DRUG

Treatment will be prescribed for GPs and they will decide the specific dosage 10-75 mg/24h.

Also known as: Tryptizol

Amitriptyline

Propranolol DRUG

Treatment will be prescribed for GPs and they will decide the specific dosage 20-120 mg/12h.

Also known as: Sumial

Propranolol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Adults (≥18) candidates for preventive treatment for migraine; those with a frequency of ≥4 monthly migraine days, and who agree to participate in the clinical trial.

You may not qualify if:

• People diagnosed with migraine who are not candidates for preventive migraine treatment
• People diagnosed with chronic migraine (\>15 days of headache per month, of which 8 are monthly migraine days)
• Not having a smartphone
• Simultaneous participation in another clinical trial
• Pregnancy or expected pregnancy during the next 3 months
• Lactation
• People with migraine who already receive preventive treatment.
• People on chronic treatment with opioids or other analgesics or NSAIDs that are not used for the symptomatic treatment of migraine, for example, osteoarthritis.
• People who, in the opinion of the clinician, have an absolute contraindication to one of the study drugs or who cannot perform the trial procedures:
• Hypersensitivity to any of the study drugs / Heart block or severe bradycardia / Concomitant treatment with verapamil or diltiazem / Active cardiovascular pathology (recent heart attack, angina, Raynaud's phenomenon) / Major depression or active treatment with antidepressants (including monoamine oxidase inhibitors and St. John's wort) / Other psychiatric illnesses or active treatment with antipsychotics or lithium / Severe liver disease or kidney failure / Parkinson's disease or other extrapyramidal disorders / Epilepsy (diagnosis and/or active treatment) / Any other contraindication that, in the opinion of the clinician, prevents participation in the clinical trial

Sponsors & Collaborators

• Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina: lead
• Institut Català de la Salut: collaborator
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: collaborator

Related Publications (1)

• Giner-Soriano M, Morros R, Monfa R, Ouchi D, Fernandez-Garcia S, Vedia C, Bonet Monne S, Calvo Martinez EM, Copetti Fanlo S, Morollon N, Belvis Nieto R, Delgado-Espinoza CE, Garcia-Sangenis A. Comparison of the effectiveness of first-line preventive treatment of migraine in primary care: study protocol for a pragmatic clinical trial (PREMI study). Trials. 2025 Aug 26;26(1):311. doi: 10.1186/s13063-025-08961-0.

  PMID: 40859286 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Topiramate; Flunarizine; Amitriptyline; Propranolol

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes

Central Study Contacts

Maria Giner-Soriano

CONTACT

+34 93 482 4110; mginer@idiapjgol.info

Ana Garcia-Sangenis

CONTACT

+34 93 482 4651; agarcia@idiapjgol.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: July 12, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share