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Atrial FibrillationPhase 3BRAKE-AFNCT03718273

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

A Phase 3 study testing Ivabradine and Digoxin in people with Atrial Fibrillation and Heart Diseases, run by Adolfo Fontenla at 10 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation, Heart Diseases
What is being tested?
Ivabradine and Digoxin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
10 sitesSpain
Study dates
19 Oct 2018to 30 Jun 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • Hospital Universitario de Burgos

    Burgos, 09006

  • Hospital Universitario Puerta de Hierro

    Madrid, 28022

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario de Getafe

    Madrid, 28905

  • Hospital Universitario Rey Juan Carlos

    Madrid, 28933

  • Hospital Virgen de la Salud

    Toledo, 45004

Other trials in Spain

About this study

Official title: 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.

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.

Read the 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.

Being tested
Ivabradine, Digoxin
Keywords
Ivabradine, Digoxin, Atrial Fibrillation, Heart rate control
Medical subject headings
Atrial Fibrillation, Heart Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvabradineDrug

    Also called Ivabradine 5 mg

    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

  • DigoxinDrug

    Also called Digoxin 0,25 mg

    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.

Study groups in NCT03718273
Study groupRoleWhat they receive
DigoxinActive comparatorDigoxin 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,
Receives: Drug: Digoxin
IvabradineExperimentalIvabradine 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.
Receives: Drug: Ivabradine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Heart rate reduction.

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

    Measured: 3 months

  2. 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.

    Measured: 3 months

Secondary outcomes (14)

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

    Percentage of patients who experience a reduction in the scale of atrial fibrillation. symptoms according to the EHRA Score modified.

    Measured: Months 1 and 3.

  2. 6 minute walk test (6MWT).

    Increase in meters in the 6MWT.

    Measured: Baseline and after 3 months.

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

    Increase in the score obtained in global quality of life parameters analyzed by the SF-36 questionnaire.

    Measured: At baseline and 3 months.

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

    Increase in the score obtained in parameters of quality of life quality of life associated with AF analyzed by the AFEQT questionnaire.

    Measured: At baseline and 3 months

  5. Reduction of the daytime Health rate.

    Reduction of the average daytime Heart Rate (HR) recorded in Holter-ECG

    Measured: 1 month

  6. Reduction of resting Health Rate.

    Reduction of resting heart rate (HR) recorded on one electrocardiogram (ECG).

    Measured: 1 and 3 months

  7. Reduction of the maximum heart rate (HR) recorded.

    Reduction of the maximum HR recorded in Holter-ECG

    Measured: 1 and 3 months

  8. Reduction of the mean HR recorded.

    Reduction of the mean HR in 24 hours recorded in Holter-ECG .

    Measured: 1 and 3 months

  9. Reduction of the HR delta.

    Reduction of the HR delta (difference between maximum HR and mean HR in 24 hours) recorded in Holter-ECG.

    Measured: 1 and 3 months

  10. Reduction of HR in moderate exercise.

    Reduction of HR in moderate exercise (maximum HR measured by Holter-ECG during the 6-minute walk test.

    Measured: 3 months

  11. Percentage of patients with non-severe bradycardia.

    Percentage of patients who experience non-severe bradycardia during the study treatment.

    Measured: 1 and 3 months

  12. Percentage of patients who experience any adverse reaction.

    Percentage of patients who experience any adverse reaction to the study drugs.

    Measured: 1 and 3 months

  13. Percentage of patients who voluntarily abandon the study drugs.

    Percentage of patients who voluntarily abandon the study drugs.

    Measured: 3 months

  14. Proportion of hospitalizations, emergency visits and mortality due to a major cardiovascular event.

    Proportion of patients experiencing hospitalizations, emergency visits and mortality due to a major cardiovascular event during treatment with the study drug.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2018
  2. Study start19 Oct 2018
  3. Primary completion22 Feb 2022
  4. Study completion30 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03718273
Sponsor's protocol ID
BRAKE-AF
Other IDs
2018-001936-23, 2018
Acronym
BRAKE-AF
Status last verified
Oct 2022
First submitted
18 Oct 2018
Last updated
7 Oct 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31631048

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ivabradine and Digoxin in people with Atrial Fibrillation and Heart Diseases, run by Adolfo Fontenla at 10 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Heart rate reduction. (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03718273, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2022.

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