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

Comparison of the Effectiveness of First-line Preventive Treatment of Migraine in Primary Care: a Pragmatic Clinical Trial [PREMI Study]

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Topiramate; Drug: Flunarizine; Drug: Amitriptyline; Drug: Propranolol

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maria Giner-Soriano; Phone Number: +34 93 482 4110; Email: mginer@idiapjgol.info
• Study Contact Backup: Name: Ana Garcia-Sangenis; Phone Number: +34 93 482 4651; Email: agarcia@idiapjgol.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topiramate; 25-100 mg/12h, V.O., during 12 weeks	Drug: Topiramate; Treatment will be prescribed for GPs and they will decide the specific dosage 25-100 mg/12h.; Other Names: Acomicil
Experimental: Flunarizine; 2,5-10 mg/24h, V.O., during 12 weeks	Drug: Flunarizine; Treatment will be prescribed for GPs and they will decide the specific dosage 2,5-10 mg mg/24h.; Other Names: Sibelium
Experimental: Amitriptyline; 10-75 mg/24h, V.O., during 12 weeks	Drug: Amitriptyline; Treatment will be prescribed for GPs and they will decide the specific dosage 10-75 mg/24h.; Other Names: Tryptizol
Active Comparator: Propranolol; 20-120 mg/12h, V.O., during 12 weeks	Drug: Propranolol; Treatment will be prescribed for GPs and they will decide the specific dosage 20-120 mg/12h.; Other Names: Sumial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculate the rate of responders (reduction of at least 50% in monthly migraine days compared to baseline)	Proportion of patients responding at 12 weeks from start of treatment; <25% change in mean number of MMD: non-responders, 25-49%: partial responders, 50-75%: responders, >75%: excellent responders.	12 weeks
Evaluate effectiveness before completing the clinical trial	Change in mean number of MMDs at 4 and 8 weeks from baseline.	4, 8 and 12 weeks
Estimate the reduction in the intensity of migraine attacks	Reduction in the mean number of moderate-severe MMD at 4, 8 and 12 weeks from the start of treatment.	4, 8 and 12 weeks
Estimate the prevalence of symptoms associated with migraine	Proportion of patients with associated symptoms at 12 weeks from the start of treatment; photophobia, phonophobia, nausea.	12 weeks
Evaluate adherence to preventive treatment	Proportion of adherent and non-adherent patients (according to taking [yes/no] of the study treatment with the prescribed dosage) at 12 weeks from the start of treatment.	12 weeks
Estimate the reduction in the use of symptomatic treatment drugs used to treat migraine attacks (analgesics, NSAIDs, triptans, others).	Change in the mean number of drugs used for symptomatic treatment at 4, 8 and 12 weeks from baseline.	4, 8 and 12 weeks
Evaluate reconsultation visits due to migraine attacks	Reconsultations: Type of consultation (PCC, PC emergency, hospital, hospital emergency). Number of consultations after 12 weeks from the start. Number of medical tests performed relacionadas con la migraña.	4, 8 and 12 weeks
Evaluate improvement in quality of life and patient satisfaction	Change in EQ-5D-5L questionnaire at 12 weeks from baseline. Including Visual Analogue Scale (0-100). Lower scores means worse health condition.	12 weeks
Analyze the differences between men and women regarding study drugs effectiveness.	Result comparison change in mean number of MMDs adjusted by sex	4, 8 and 12 weeks
Estimate the disability associated with migraine attacks according to number of paticipans reporting temporary work disability, absenteeism, presenteeism.	Change in the number of ILT days, absenteeism, presenteeism at 12 weeks from the start of treatment.	12 weeks
Incidence of adverse events of the four drugs used in the preventive treatment of migraine .	Number of adverse events	12 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 8, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 8, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Primary care; Migraine; Preventive treatment; Monthly Migraine Days (MMD)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Anticonvulsants; Antidepressive Agents, Tricyclic; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic Uptake Inhibitors; Propranolol; Amitriptyline; Flunarizine; Topiramate
• Other Study ID Numbers: IJG-PREMI-2024; 2024-513597-22-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All publications will be free and open access. Publications of clinical trial results are planned in national and/or international scientific journals and in communications to conferences. Results will also be communicated to scientific societies and other actors involved in decision-making in the healthcare field, as well as through dissemination activities to patients and citizens in general.

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