IvaBRAdine blocK of Funny Current for Heart Rate Control in permanEnt Atrial Fibrillation. (BRAKE-AF Study).

NCT03718273 | Completed Phase 3

• 2 other identifiers: BRAKE-AF2018-001936-23
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 10

Brief Summary

The BRAKE-AF Study is a phase III, randomised, controlled, multicentric, open-label clinical trial to prove the noninferiority of ivabradine versus digoxin in the treatment of permanent atrial fibrillation. The total duration of the study is 3 years, with 24 months of enrolment, treatment and follow-up.

Conditions

Atrial Fibrillation; Heart Diseases

Keywords

Ivabradine; Digoxin; Atrial Fibrillation; Heart rate control

Outcome Measures

Primary Outcomes (2)

• Heart rate reduction.

  Reduction of the mean daytime heart rate registered in Holter- electrocardiogram (ECG) after treatment with Ivabradine or Digoxin.

  3 months

• Serious adverse events

  Proportion of patients experiencing syncope, severe bradycardia or any serious adverse reaction requiring hospitalization, emergency visit or death of the patient during treatment with Ivabradine or Digoxin.

  3 months

Secondary Outcomes (14)

• Reduction in the scale of atrial fibrillation (AF) symptoms according to the European Hearth Rhythm Association (EHRA) Score modified.

  Months 1 and 3.

• 6 minute walk test (6MWT).

  Baseline and after 3 months.

• Quality-of-Life Short Form 36 (SF-36) Health Survey (QoL SF-36) Score.

  At baseline and 3 months.

• The Atrial Fibrillation Effect on Quality-of-Life (QoL AFEQT) score.

  At baseline and 3 months

• Reduction of the daytime Health rate.

  1 month

Study Arms (2)

Digoxin

ACTIVE COMPARATOR

Digoxin 0,25 mg. The initial dose will be based on whether there are factors such as age over 80 years, weight under 60 kg and creatinine clearance \<60ml / min,

Drug: Digoxin

Ivabradine

EXPERIMENTAL

Ivabradine 5 mg, twice a day the first month administered by mouth. If the tolerance is good, the dose will be increased to 7.5 mg on month 2 and will continue until the third month.

Drug: Ivabradine

Interventions

Ivabradine DRUG

Ivabradine 5 mg, twice a day the first month administered by mouth. If the tolerance is good, the dose will be increased to 7.5 mg on month 2 and will continue until the third month. Patients with 75 or more years of age will receive an initial dose of 2.5 mg / twice a day, which can be increased to 5 mg / twice a day in week 7 and to 7.5 mg in month 1 if the tolerance has been good

Also known as: Ivabradine 5 mg

Ivabradine

Digoxin DRUG

The initial dose will be based on whether there are factors such as age over 80 years, weight less than 60 kg and creatinine clearance \<60ml / min, if there is no factor, the oral dose will be 0.25mg / 24h. If there are 2 factors, the dose will be 0.15 mg / 24 h. and if there are 2 or 3 factors, the dose will be 0.10 mg / 24 h.

Also known as: Digoxin 0,25 mg

Digoxin

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Permanent Atrial Fibrillation (AF) at the time of randomization, with no prospect of cardioversion, antiarrhythmic treatment with group I or III drugs, or pulmonary vein ablation.
• Symptoms attributable to AF associated with the presence of at least one of the following inadequate Heart rate (HR) control criteria:
• Be receiving treatment with beta-blockers or non-dihydropyridine calcium channel blockers (verapamil or diltiazem) at the maximum dose recommended or tolerated by the patient.
• Be able to voluntarily give their informed consent.

You may not qualify if:

• Previous treatment or patients with a known contraindication to Ivabradine or Digoxin or to any excipient of both drugs.
• Paroxysmal or intermittent complete atrioventricular (AV) block in patients not carrying a pacemaker.
• Decompensated heart failure requiring inotropic and I or intravenous diuretics in the week prior to randomization or in New York Heart Association (NYHA) functional class IV or on the cardiac transplant waiting list,
• Acute pericarditis, acute myocarditis or constrictive pericarditis.
• Obstructive hypertrophic cardiomyopathy.
• Valvular disease requiring surgical or percutaneous correction.
• Medical causes that justify poor control of heart rate: fever' anemia, hyperthyroidism, pheochromocytoma' etc.
• Severe hypotension (blood pressure \<90/50 mmHg).
• Concomitant treatment with potent cytochrome P450 3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, oral erythromycin, josamycin, telithromycin) HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone.
• Severe renal insufficiency (CrCl \<30 ml/Kg/min) or in a hemodialysis program.
• Severe hepatic insufficiency.
• Major surgery (including cardiac surgery) in the month prior to randomization.
• Severe concomitant illness that supposes a llfe expectancy of less than one year.
• Impossibility of carrying out scheduled visits to the protocol.
• Woman of childbearing age (under 50 years of age, except for those who present a gynecological report that proves the presence of menopause) and women who are breastfeeding.

Sponsors & Collaborators

• Adolfo Fontenla: lead
• Spanish Clinical Research Network - SCReN: collaborator
• Carlos III Health Institute: collaborator

Study Sites (10)

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28022, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Getafe

Madrid, 28905, Spain

Location

Hospital Universitario Rey Juan Carlos

Madrid, 28933, Spain

Location

Hospital Virgen de la Salud

Toledo, 45004, Spain

Location

Related Publications (1)

• Fontenla A, Lopez-Gil M, Tamargo-Menendez J, Matia-Frances R, Salgado-Aranda R, Rey-Blas JR, Miracle-Blanco A, Mejia-Martinez E, Pastor-Fuentes A, Toquero-Ramos J, Arias MA, Montilla I, Gomez de la Camara A, Arribas F; BRAKE-AF investigators. Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project. Rev Esp Cardiol (Engl Ed). 2020 May;73(5):368-375. doi: 10.1016/j.rec.2019.09.004. Epub 2019 Oct 17. English, Spanish.

  PMID: 31631048 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Heart Diseases

Interventions

Ivabradine; Digoxin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Adolfo Fontenla, MD, PhD

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Adolfo Fontenla, MD, PhD

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 24, 2018
• Study Start: October 19, 2018
• Primary Completion: February 22, 2022
• Study Completion: June 30, 2022
• Last Updated: October 7, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10)