Efficacy of Ivabradine in Patient With Both Persistent Atrial Fibrillation and Heart Failure With Reduce Ejection Fraction

NCT ID: NCT04308031

Last Updated: 2020-03-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-26
• Study Completion Date: 2020-12-31

Brief Summary

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Previous studies have shown that rate control strategy in AF is non-inferior to rhythm control strategy, in terms of stroke and mortality risk. In addition, rate control strategy is associated with lower risk of hospitalization and non-cardiovascular mortality. Therefore, rate control is an essential strategy to improve quality of life, decrease morbidity and prevent tachycardia-induced cardiomyopathy in AF patients. The recommended rate control agents include beta-blocker, nondihydropyridine calcium-channel blocker (CCB), digoxin and amiodarone. However, in heart failure with reduced ejection fraction patient, the medication of rate control were beta-blocker than digoxin. But several clinical observation study show excess mortality in AF patients. Ivabradine, a If inhibitor, it is well-established that a pacemaker current, If current, is functionally expressed in the sinus node . Previous studies have shown that Ivabradine, If inhibitor, significantly reduces sinus rate and improves prognosis in patients with systolic heart failure. Interestingly, several investigators found that hyperpolarization- activated cyclic nucleotidylated channel 4 current (HCN4), the main isoform of the channel responsible for If current, is also functionally expressed in the Atrioventricular node(AV node). Recent data have shown that inhibition of If current slows AV node conduction in animals and humans. Thus, we want to compare the effect of Ivabradine on ventricular rate with digoxin in this study.

Conditions

Atrial Fibrillation; Ivabradine; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ivabradine

Subject will be randomly assigned to either Ivabradine or Digoxin group. Ivabradine starting dose is 2.5 mg twice daily(BID). ECG will be performed at each visit during the treatment phase and dose will be adjusted based on the heart rate result from the ECG. Total treatment phase is 16 weeks ( 4 months).

Group Type: EXPERIMENTAL

Ivabradine 5 mg [Corlanor]

Intervention Type: DRUG

Starting dose: Ivabradine 2.5mg twice daily (BID) Max Dose: Ivabradine 7.5 mg twice daily (BID)

Digoxin

Subject will be randomly assigned to either Ivabradine or Digoxin group. Digoxin starting dose is 0.125mg once daily(QD) in estimated Glomerular filtration rate(eGFR)\>60， 0.125mg every other day (QOD) in estimated Glomerular filtration rate(eGFR)\<60. Dose adjustment will be based on heart rate result from ECG performed at each treatment visit and Digoxin level from blood sample collected from each visit during treatment phase. Total treatment phase is 16 weeks ( 4 months).

Group Type: ACTIVE_COMPARATOR

Digoxin 0.25 mg

Intervention Type: DRUG

Starting dose: 0.125mg once daily (QD) in estimated Glomerular filtration rate(eGFR)\>60， 0.125mg once every other day (QOD) in estimated Glomerular filtration rate(eGFR)\<60 Max dose: 0.25 once daily (QD)

Interventions

Ivabradine 5 mg [Corlanor]

Starting dose: Ivabradine 2.5mg twice daily (BID) Max Dose: Ivabradine 7.5 mg twice daily (BID)

Intervention Type: DRUG

Digoxin 0.25 mg

Starting dose: 0.125mg once daily (QD) in estimated Glomerular filtration rate(eGFR)\>60， 0.125mg once every other day (QOD) in estimated Glomerular filtration rate(eGFR)\<60 Max dose: 0.25 once daily (QD)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. The patient with persistent or permanent atrial fibrillation(24hr ECG) with HFrEF and HFmrEF.

2. After maximal tolerance dose beta-blocker(Bisoprolol 20mg/day，Carvedilol 50mg/day) or intolerant to beta-blocker the resting heart rate from ECG is still faster than 100 or resting heart rate from ECG is greater than 80 but still with symptoms of short of breath and palpitation.

3. Stable heart rhythm medication.(no change of medication in recently one week)

4. Age 20 to 90 years old.

5. The subject must be an adult who can read himself/herself and walk independently.

Exclusion Criteria

1. Used medication with interaction with digoxin : Clarithromycin, Erythromycin, Azithromycin, ritonavir, lopinavir/ritonavir, Doxycycline, Minocycline, tetracycline。

2. Used medication with interaction with ivabradine: voriconazole, posaconazole, fluconazole, Ombitasvir, Dasabuvir, Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenobarbital, Phenytoin, Rifampicin

3. Cardiogenic shock.

4. History of symptomatic bradycardia.

5. Renal insufficiency:eGFR<30 ml/min/1.73m2

6. Pregnancy

7. Heart failure due to congenital heart

8. Severe hypotension(<90/50mmHg)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chun-Yao Huang

OTHER

Sponsor Role: lead

Responsible Party

Chun-Yao Huang

Attending physician

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Taipei Medical University Hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

N201801089

Identifier Type: -

Identifier Source: org_study_id