Heart rate control in patients with chronic atrial fibrillation. MedDRA version: 20.0 Level: LLT Classification code 10071668 Term: Permanent atrial fibrillation System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Digoxina Kern Pharma 0.25 mg comprimidos
Product Name: Digoxine
Pharmaceutical Form: Tablet
INN or Proposed INN: DIGOXIN
CAS Number: 20830-75-5
Trade Name: Ivabradina Kern Pharma 5 mg or
Sponsors
Dr. Adolfo Fontenla Cerezuela
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age equal to or greater than 18 years. 2. Permanent FA at the time of randomization, with no prospect of cardioversion, antiarrhythmic treatment with group I or III drugs, or pulmonary vein ablation. 3. Symptoms attributable to AF associated with the presence of at least one of the following inadequate FC control criteria: a) HR at rest> 110 bpm (on ECG performed in the 14 days prior to inclusion). b) 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). 4. 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. 5. Be able to voluntarily give their informed consent (the subject himself, his legal representative or an impartial witness). 6. Blood 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 FC 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. 7. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1. Previous treatment or known contraindication to Ivabradine or Digoxin. 2. Paroxysmal or intermittent complete AV block in patients not carrying a pacemaker. 3. Decompensated heart failure requiring inotropic and / or intravenous diuretics in the week prior to randomization or in NYHA functional class IV or on the cardiac transplant waiting list. 4. Acute pericarditis, acute myocarditis or constrictive pericarditis. 5. Obstructive hypertrophic cardiomyopathy. 6. Valvular disease requiring surgical or percutaneous correction. 7. Medical causes that justify poor control of heart rate: fever, anemia, hyperthyroidism, pheochromocytoma, etc. 8. Severe hypotension (blood pressure <90/50 mmHg). 9. 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. 10. Severe renal insufficiency (CrCl <30 ml / Kg / min) or in a hemodialysis program. 11. Severe hepatic insufficiency. 12. Major surgery (including cardiac surgery) in the month prior to randomization. 13. Severe concomitant illness that supposes a life expectancy of less than one year. 14. Impossibility of carrying out scheduled visits to the protocol. 15. Suspected pregnancy or confirmed pregnancy. 16. Participation in a clinical trial in the previous 6 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of two treatment strategies with respect to the reduction of the mean daytime HR measured with Holter-ECG at three months and compare the safety of the two treatment strategies with respect to syncope, severe bradycardia and serious adverse reactions that condition hospitalization, emergency visit or result in death.;Secondary Objective: To compare the effect of the two treatment strategies, and depending on the basic treatment, with respect to: - Symptoms according to the EHRA Score scale evaluated at one and three months of treatment. - Distance in the 6-minute test. - Quality of life parameters analyzed in the questionnaires SF-36 and AFEQT. - Average daytime FC measured with a Holter-ECG. - FC at rest measured with an ECG. - Maximum FC measured with a Holter-ECG. - Average FC in 24 hours measured with a Holter-ECG. - FC Delta (difference between maximum HR and mean HR) measured with a Holter-ECG. - FC in moderate exercise measured with a Holter-ECG during the 6-minute test). To compare the safety of the two treatment strategies with respect to: - Bradycardia not serious. - Any adverse reaction to the study drugs. - Voluntary withdrawal of the drug by the patient - Hospitalizations, emergency visits and mortality due to a major cardiovascular event during treatment with the study drugs.;Primary end point(s): Reducción de la Frecuencia Cardiaca media diurna registrada en Holter-ECG a los tres meses de tratamiento con Ivabradina o Digoxina.;Timepoint(s) of evaluation of this end point: Three months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of patients who experience a reduction in the scale of AF symptoms according to the EHRA Score modified at month and 3 months of treatment with Ivabradine or Digoxin. 2. Increase in the distance in the walking test 6 minutes after 3 months of treatment with Ivabradine or Digoxin. 3. Increase in the score obtained in global quality of life parameters analyzed by the SF-36 questionnaire after 3 months of treatment with Ivabradine or Digoxin. 4. Increase in the score obtained in parameters of quality of life quality of life associated with AF analyzed by the AFEQT questionnaire at 3 months of treatment with Ivabradine or Digoxin. 5. Reduction of the average daytime HR recorded in Holter-ECG after one month of treatment with Ivabradine or Digoxin. 6. Reduction of resting HR recorded on one ECG at one month and at 3 months of treatment with Ivabradine or Digoxin. 7. Reduction of the maximum HR recorded in Holter-ECG at one month and at 3 months of treatment with Ivabradine or Digoxin. 8. Reduction of the mean HR in 24 hours recorded in Holter-ECG at one month and at 3 months of treatment with Ivabradine or Digoxin. 9. Reduction of the HR delta (difference between maximum HR and mean HR in 24 hours) recorded in Holter-ECG at one month and at 3 months of treatment with Ivabradine or Digoxin. 10. Reduced HR in moderate exercise (maximum HR measured by Holter-ECG during the 6-minute walk test) during 3 months of treatment with Ivabradine or Digoxin.;Timepoint(s) of evaluation of this end point: Three months after the start of treatment. | — |
Countries
Spain
Contacts
Public ContactServicio de Cardiología
Dr. Adolfo Fontenla Cerezuela
Outcome results
None listed