Caffeine Consumption and Rate Control in Permanent Atrial FIBrillation: The CAFIB Trial

NCT07738523 | Recruiting Phase 2

• 1 other identifier: CEIm25-139
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The CAFIB trial is a multicenter, randomized, open-label, crossover clinical trial designed to determine whether habitual caffeine consumption in coffe adversely affects rate control in patients with permanent atrial fibrillation (AF). The rationale stems from the discrepancy between traditional clinical recommendations, which often advise patients with arrhythmias to avoid caffeine, and the growing body of evidence suggesting that moderate coffee consumption is not associated with an increased risk of AF and may even confer cardiovascular benefits. However, no randomized study has specifically investigated this issue in patients with permanent AF, a population in whom rate control remains the cornerstone of management. The primary hypothesis is that continued moderate caffeine consumption is non-inferior to caffeine abstinence regarding 24-hour mean heart rate control. Participants will be randomly assigned in a 1:1 ratio to one of two treatment sequences stratified according to baseline coffee intake (1 cup/day vs. \>1 cup/day). Owing to the nature of the intervention, the study is open-label; nevertheless, Holter recordings will be analyzed by blinded investigators, and the statistical analysis will also be performed blinded to treatment allocation to minimize bias. Eligible participants are adults with permanent AF diagnosed for more than three months, stable ventricular rate control (\<110 bpm at rest), unchanged rate-control medication for at least two months, and habitual coffee consumption of at least one caffeinated cup per day. Patients with advanced heart failure, recent major cardiovascular events, cognitive impairment, implanted cardiac pacing devices, or other conditions likely to interfere with study outcomes are excluded. The intervention compares two dietary strategies: continuation of regular caffeinated coffee consumption (at least one cup daily) versus complete caffeine abstinence, while allowing decaffeinated coffee. Energy drinks are prohibited in both groups, and participants assigned to abstinence are advised to avoid compensatory caffeine intake from other sources. No washout period is planned between crossover phases because caffeine has a biological half-life of less than 24 hours. Adherence will be assessed using caffeine consumption diaries and structured interviews at each study visit. The primary endpoint s the 24-hour mean heart rate measured by ambulatory Holter electrocardiography. Secondary endpoints include changes in mean HR from baseline, percentage of time with HR \>110 bpm or \<50 bpm, ventricular ectopic burden, symptom severity assessed using the modified EHRA classification, quality of life evaluated with the AFEQT questionnaire, circulating biomarkers of heart failure, adverse events, and changes in concomitant medical therapy. Patients will undergo three scheduled visits (baseline, 30 days, and 60 days), each including clinical assessment, ECG, 24-hour Holter monitoring, blood sampling, and quality-of-life questionnaires. Sample size calculation was based on detecting a clinically relevant difference of 5 bpm, assuming a standard deviation of 7 bpm, 80% statistical power, and a two-sided α of 0.05. After accounting for an anticipated 25% dropout rate and potential protocol deviations, a total of 50 patients (25 per treatment sequence) will be recruited. The primary analysis will follow the intention-to-treat principle, complemented by a per-protocol analysis. Statistical models will adjust for clinically relevant covariates, including age, sex, baseline heart rate, and concomitant rate-control therapy, while multivariable regression analyses will explore predictors of optimal heart rate control. The protocol acknowledges several limitations, including its open-label design, reliance on self-reported caffeine intake to assess adherence, interindividual variability in caffeine metabolism, and limited external validity to stable, habitual coffee consumers with permanent AF. Despite these limitations, CAFIB represents the first randomized trial specifically evaluating the impact of caffeine consumption on ventricular rate control in permanent AF.

Conditions

Atrial Fibrillation (AF); Permanent Atrial Fibrillation; Coffee Consumption; Caffeine Abuse

Keywords

Atrial fibrillation; Coffee; Caffeine; Heart Rate; Permanent Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• Mean Heart Rate (bpm)

  Mean Heart Rate (bpm) in 24-h Holter-ECG

  30 ± 5 days

Secondary Outcomes (3)

• Difference with baseline heart rate

  30 ± 5 days

• Symptoms Asessment

  30 ± 5 days

• Adverse Events

  30 ± 5 days

Other Outcomes (2)

• Changes in rate-control medication

  30 ± 5 days

• Premature Ventricular contraction burden

  30 ± 5 days

Study Arms (2)

Continuation of regular caffein consumption

EXPERIMENTAL

Patients will continue with their usual caffeine intake. Energy drinks intakes are prohibited.

Dietary Supplement: Dietary Caffeine Intake

Complete caffeine abstinence

NO INTERVENTION

Complete caffeine abstinence, while allowing decaffeinated coffee. Energy drinks are prohibited.

Interventions

Dietary Caffeine Intake DIETARY_SUPPLEMENT

Patients will mantain their usual caffeine consumption

Continuation of regular caffein consumption

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Permanent atrial fibrillation diagnosed for more than 3 months.
• Stable rate-control status, defined as a resting heart rate \<110 bpm without changes in rate-control medication during the previous 2 months.
• Habitual caffeine consumption (≥1 cup/day of caffeinated coffee).
• Willingness to participate in the study, including acceptance of complete caffeine abstinence for up to two months if assigned to the abstinence arm.

You may not qualify if:

• Age \<18 years or \>80 years.
• Previous diagnosis of cognitive impairment or dementia.
• Legal incapacity or inability to provide informed consent.
• Inability to understand or complete quality-of-life questionnaires.
• Presence of a cardiac implantable electronic device with pacing capability (pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronization therapy device).
• Previous successful atrioventricular node ablation.
• Decompensated heart failure (New York Heart Association class III-IV) or hospitalization for heart failure within the previous 3 months.
• Acute coronary syndrome within the previous 3 months.
• Stroke within the previous 3 months.
• Cardiac surgery within the previous 3 months.
• Severe unrepaired valvular heart disease.

Sponsors & Collaborators

• Hospital Universitario Getafe: lead
• Instituto de Investigación Sanitaria Getafe: collaborator

Study Sites (1)

Getafe University Hospital

Getafe, Madrid, 28905, Spain

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Martín Negreira-Caamaño, MD, PhD

CONTACT

+34 916839360; martin.negcam@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiology Department, Getafe University Hospital, Spain

Study Record Dates

• First Submitted: July 25, 2026
• First Posted: July 31, 2026
• Study Start: July 27, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: July 31, 2026

Record last verified: 2026-07

Locations

ES (1)