- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03718273
IvaBRAdine blocK of Funny Current for Heart Rate Control in permanEnt Atrial Fibrillation. (BRAKE-AF Study). (BRAKE-AF)
A Phase III Clinical Trial to Compare Ivabradine Versus Digoxin in the Heart Rate Control in Patients With Permanent Atrial Fibrillation Under Treatment With Beta-blockers or Calcium Antagonists.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a non-commercial, investigator-driven clinical study funded through a public competitive call by Instituto de Salud Carlos III, Spanish Ministry of Economy (PI17/01272).
The study is coordinated by the main investigator from Hospital Universitario 12 de Octubre in Madrid; the sponsorship is performed by Dr. Adolfo Fontenla (Hospital Universitario 12 de Octubre). Several responsibilities are delegated to the Clinical Research Unit (Hospital 12 de Octubre, Madrid, Spain).
The study was planned according to the Good Clinical Practices. BRAKE-AF Study has been approved by the Ethics Committee and Spanish Health Authorities. All participating patients must give written informed consent before any study procedure occur.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Burgos, Spain, 09006
- Hospital Universitario de Burgos
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Madrid, Spain, 28040
- Fundación Jiménez Díaz
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Madrid, Spain, 28034
- Hospital Universitario Ramon y Cajal
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Madrid, Spain, 28040
- Hospital Clinico San Carlos
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Madrid, Spain, 28041
- Hospital Universitario 12 de Octubre
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Madrid, Spain, 28046
- Hospital Universitario La Paz
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Madrid, Spain, 28905
- Hospital Universitario de Getafe
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Madrid, Spain, 28022
- Hospital Universitario Puerta de Hierro
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Madrid, Spain, 28933
- Hospital Universitario Rey Juan Carlos
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Toledo, Spain, 45004
- Hospital Virgen de la Salud
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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:
- HR at rest > 110 bpm (on ECG -electrocardiogram- performed in the 14 days prior to inclusion).
- HR at rest between 80 and 110 bpm (on ECG performed in the 14 days prior to inclusion) and at least one of the following criteria:
i. HR in exercise of moderate intensity > 130 bpm (measured in an ergometry or in a Holter-ECG performed in the 60 days prior to inclusion).
ii. Average daytime HR > 80 bpm (measured on a Holter-ECG performed in the 60 days prior to inclusion).
- 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.
- B|ood test carried out in the 6 months prior to inclusion' including: blood count, thyroid hormones and creatinine, in order to rule out secondary causes of poor HR control. The creatinine figure will be used to calculate the creatinine clearance in order to adjust the dose of patients who are randomized to the Digoxin group.
- Transthoracic echocardiogram to rule out, eg, severe valvular heart disease, hypertrophic cardiomyopathy. The one performed in the year prior to inclusion in the study will be considered acceptable provided that the patient's clinical situation has been stable in that period of time.
Exclusion Criteria:
- 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.
- Participation in a clinical trial in the previous 6 months.
- Patients with acute myocardial infarction or unstable angina.
- Patient with a recent stroke.
- Patients with congenital long QT syndrome or treated with drugs that prolong this interval.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Digoxin
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,
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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.
Other Names:
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Experimental: Ivabradine
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.
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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
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Heart rate reduction.
Time Frame: 3 months
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Reduction of the mean daytime heart rate registered in Holter- electrocardiogram (ECG) after treatment with Ivabradine or Digoxin.
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3 months
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Serious adverse events
Time Frame: 3 months
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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.
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3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reduction in the scale of atrial fibrillation (AF) symptoms according to the European Hearth Rhythm Association (EHRA) Score modified.
Time Frame: Months 1 and 3.
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Percentage of patients who experience a reduction in the scale of atrial fibrillation.
symptoms according to the EHRA Score modified.
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Months 1 and 3.
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6 minute walk test (6MWT).
Time Frame: Baseline and after 3 months.
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Increase in meters in the 6MWT.
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Baseline and after 3 months.
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Quality-of-Life Short Form 36 (SF-36) Health Survey (QoL SF-36) Score.
Time Frame: At baseline and 3 months.
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Increase in the score obtained in global quality of life parameters analyzed by the SF-36 questionnaire.
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At baseline and 3 months.
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The Atrial Fibrillation Effect on Quality-of-Life (QoL AFEQT) score.
Time Frame: At baseline and 3 months
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Increase in the score obtained in parameters of quality of life quality of life associated with AF analyzed by the AFEQT questionnaire.
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At baseline and 3 months
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Reduction of the daytime Health rate.
Time Frame: 1 month
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Reduction of the average daytime Heart Rate (HR) recorded in Holter-ECG
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1 month
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Reduction of resting Health Rate.
Time Frame: 1 and 3 months
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Reduction of resting heart rate (HR) recorded on one electrocardiogram (ECG).
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1 and 3 months
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Reduction of the maximum heart rate (HR) recorded.
Time Frame: 1 and 3 months
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Reduction of the maximum HR recorded in Holter-ECG
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1 and 3 months
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Reduction of the mean HR recorded.
Time Frame: 1 and 3 months
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Reduction of the mean HR in 24 hours recorded in Holter-ECG .
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1 and 3 months
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Reduction of the HR delta.
Time Frame: 1 and 3 months
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Reduction of the HR delta (difference between maximum HR and mean HR in 24 hours) recorded in Holter-ECG.
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1 and 3 months
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Reduction of HR in moderate exercise.
Time Frame: 3 months
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Reduction of HR in moderate exercise (maximum HR measured by Holter-ECG during the 6-minute walk test.
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3 months
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Percentage of patients with non-severe bradycardia.
Time Frame: 1 and 3 months
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Percentage of patients who experience non-severe bradycardia during the study treatment.
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1 and 3 months
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Percentage of patients who experience any adverse reaction.
Time Frame: 1 and 3 months
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Percentage of patients who experience any adverse reaction to the study drugs.
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1 and 3 months
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Percentage of patients who voluntarily abandon the study drugs.
Time Frame: 3 months
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Percentage of patients who voluntarily abandon the study drugs.
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3 months
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Proportion of hospitalizations, emergency visits and mortality due to a major cardiovascular event.
Time Frame: 3 months
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Proportion of patients experiencing hospitalizations, emergency visits and mortality due to a major cardiovascular event during treatment with the study drug.
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3 months
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Adolfo Fontenla, MD, PhD, Hospital Universitario 12 de Octubre
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BRAKE-AF
- 2018-001936-23 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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