Mediterranean Diet Plus Extravirgin Olive Oil in the Prevention of Recurrent Arrhythmias. The PREDIMAR (PREvención Con DIeta Mediterránea de Arritmias Recurrentes) Trial (PREDIMAR)

Randomized Trial of Mediterranean Diet Plus Extravirgin Olive Oil in the Prevention of Recurrent Arrhythmias. The PREDIMAR (PREvención Con DIeta Mediterránea de Arritmias Recurrentes) Trial

Background: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and represents a high priority public health problem, as in a few decades it will become a possibly unsustainable load for the national health system. Preventive and therapeutic strategies based on the best possible scientific evidence are required. Ablation therapy, despite being the most effective approach, is associated with a 30-35% arrhythmic recurrence rate. An intervention with Mediterranean diet and extra virgin olive oil (EVOO) has proven effective in primary prevention and reduced the incidence of AF in high-risk subjects in a recent, large, randomized trial (PREDIMED).

Methods: Parallel, randomized, multicenter nutritional intervention trial in 640 patients with AF treated with catheter ablation. Two groups will be randomized in a 1:1 ratio: 1) intervention with Mediterranean diet and EVOO; 2) usual care (control group). The primary objective will be the incidence of atrial tachyarrhythmias for two years after ablation. At least 190 recurrences are expected after 2 years (median) of follow-up. A relative risk of 0.7 is assumed and statistical power of 80%. Follow-up visits will be scheduled at 3, 6, 12, 18 and 24 months. In addition to the in-person visits, event monitors will be used to document episodes. Dietary intervention will be carried out by nutritionists who will use methods adapted from the PREDIMED trial with contacts every 2 months. 1 liter of EVOO per week will be provided for free in the intervention arm. Inflammatory markers will be analyzed in both groups during follow-up. Cox models will be used to estimate adjusted hazard ratios.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation; Atrial Arrhythmia
• Intervention / Treatment: Dietary supplement: Mediterranean diet plus extra virgin olive oil

• Study Type: Interventional
• Enrollment (Actual): 720
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28033
    • Teresa Barrio López

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with symptomatic paroxysmal AF (with evidence of more than one symptomatic episode in the last year and at least one documented episode) upon whom catheter ablation is performed.
• Patients with persistent symptomatic AF upon whom catheter ablation is performed.

Exclusion Criteria:

• Serious medical condition that prevents dietary intervention (gastrointestinal disease with intolerance to fats, advanced malignancy, neurological, psychiatric or severe endocrine disease)
• Any other pathology or medical condition that limits survival to less than one year; Immunodeficiency or HIV-positive,
• Consumption of illegal drugs,
• Chronic alcoholism or total consumption of alcohol >80 g/d
• Body mass index > 40 kg/m 2,
• Difficulty or major inconvenience with changing dietary habits, inability to follow a style of Mediterranean diet, low probability of changing dietary habits according to the models of Prochaska and Diciemente (Nigg, 1999)
• History of food allergy or hypersensitivity to any component of EVOO
• Participation in a clinical trial carried out with drugs or use of a drug in experimental state during the year prior to inclusion
• Institutionalized patients for chronic treatment, with lack of autonomy and with inability to perform the clinical follow-up,
• Impossibility of telephone contact
• Patients with acute infection or inflammatory process (e.g. pneumonia) may be included in the study three months after the resolution of the infectious symptoms.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mediterranean diet plus extra virgin olive oil; These patients will receive 1 liter of EVOO per week free of charge and dietary advice on how to follow a Mediterranean diet with contacts every two months.	Dietary supplement: Mediterranean diet plus extra virgin olive oil; The patients in the intervention group will receive 1 liter of EVOO per week free of charge and dietary advice on how to follow a Mediterranean diet with contacts every two months. Dietary intervention will be carried out by nutritionists with previous experience in the PREDIMED study. All of them were registered, trained and certified for developing the PREDIMED intervention protocol that is similar to the one to be carried out in this study. The theoretical sessions with patients about dietary education shall be conducted in telephone form, using the internet and sending comprehensive written material to their homes that includes recipes, shopping lists, menus and explanations of typical food in the Mediterranean diet
No Intervention: no specific diet; The control group will be assigned to the usual care and patients assigned to this group will not receive any special intervention to follow a particular diet, as occurs in the current clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
atrial tachyarrhythmias documented by electrocardiogram or recorder device	Atrial tachyarrhythmia is defined at any fast rate (>100 bpm) of supraventricular origin lasting more than 30 seconds and that is documented by ECG, Holter or event monitor.	mean follow up of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial fibrillation documented by electrocardiogram or recorder device	AF is defined at any irregular atrial rhythm lasting more than 30 seconds and that is documented by ECG, Holter or event monitor. AF may or may not be symptomatic.	mean follow up of 2 years
changes in Inflammatory markers in blood samples	Prior to ablation blood samples will be collected for determination of inflammatory parameters in a subsample of the study (neutrophil to lymphocyte ratio, TNF-alpha, fibrinogen, IL-2, IL6, IL-8, C-reactive protein). At 3 and 12 months of follow-up the determination of these parameters will be repeated.	1 year follow up
Changes in quality of life measured by SF-36 questionnaire	Change in quality of life during the follow up measured by SF-36 questionnaire	mean follow up of 2 years

Collaborators and Investigators

• Sponsor: Fundación de investigación HM
• Collaborators: University of Navarra; Hospital General Universitario de Alicante; University Hospital Virgen de las Nieves
• Investigators: Study Chair: Miguel A Martinez González, MD, PhD, MPH, University of Navarra; Study Director: Jesus Almendral Garrote, MD, PhD, FESC, Fundación HM; Principal Investigator: Teresa Barrio Lopez, MD, PhD, Fundación HM

Publications and helpful links

General Publications

• Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Martinez-Gonzalez MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013 Apr 4;368(14):1279-90. doi: 10.1056/NEJMoa1200303. Epub 2013 Feb 25. Erratum In: N Engl J Med. 2014 Feb 27;370(9):886.
• Martinez-Gonzalez MA, Toledo E, Aros F, Fiol M, Corella D, Salas-Salvado J, Ros E, Covas MI, Fernandez-Crehuet J, Lapetra J, Munoz MA, Fito M, Serra-Majem L, Pinto X, Lamuela-Raventos RM, Sorli JV, Babio N, Buil-Cosiales P, Ruiz-Gutierrez V, Estruch R, Alonso A; PREDIMED Investigators. Extravirgin olive oil consumption reduces risk of atrial fibrillation: the PREDIMED (Prevencion con Dieta Mediterranea) trial. Circulation. 2014 Jul 1;130(1):18-26. doi: 10.1161/CIRCULATIONAHA.113.006921. Epub 2014 Apr 30. Erratum In: Circulation. 2019 Dec 10;140(24):e939.
• Goni L, de la O V, Barrio-Lopez MT, Ramos P, Tercedor L, Ibanez-Criado JL, Castellanos E, Ibanez Criado A, Macias Ruiz R, Garcia-Bolao I, Almendral J, Martinez-Gonzalez MA, Ruiz-Canela M. A Remote Nutritional Intervention to Change the Dietary Habits of Patients Undergoing Ablation of Atrial Fibrillation: Randomized Controlled Trial. J Med Internet Res. 2020 Dec 7;22(12):e21436. doi: 10.2196/21436.
• Barrio-Lopez MT, Ruiz-Canela M, Ramos P, Tercedor L, Ibanez Criado JL, Ortiz M, Goni L, Ibanez Criado A, Macias-Ruiz R, Garcia-Bolao I, Martinez-Gonzalez MA, Almendral J. PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study in patients with atrial fibrillation: Rationale, design and methods. Am Heart J. 2020 Feb;220:127-136. doi: 10.1016/j.ahj.2019.10.009. Epub 2019 Oct 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2017
• Primary Completion (Actual): January 31, 2020
• Study Completion (Anticipated): January 31, 2022

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 12, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2020
• Last Update Submitted That Met QC Criteria: April 8, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Ablation; Mediterranean Diet; Extra Virgin Olive Oil
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Atrial Fibrillation; Arrhythmias, Cardiac
• Other Study ID Numbers: MeDiet+EVOO after AF ablation

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No