Atrial FibrillationPhase 3NCT04308031
Efficacy of Ivabradine in Patient With Both Persistent Atrial Fibrillation and Heart Failure With Reduce Ejection Fraction
A Phase 3 study testing Ivabradine 5 mg [Corlanor] and Digoxin 0.25 mg in people with Atrial Fibrillation and Ivabradine, run by Chun-Yao Huang at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 90 years
- Conditions the study is for
- Atrial Fibrillation, Ivabradine, Heart Failure
- What is being tested?
- Ivabradine 5 mg [Corlanor] and Digoxin 0.25 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteTaiwan
- Study dates
- 26 Aug 2018to 31 Dec 2020
- 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 20 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient with persistent or permanent atrial fibrillation(24hr ECG) with HFrEF and HFmrEF.
- 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.
- Stable heart rhythm medication.(no change of medication in recently one week)
- Age 20 to 90 years old.
- The subject must be an adult who can read himself/herself and walk independently.
Who cannot join
- Used medication with interaction with digoxin : Clarithromycin, Erythromycin, Azithromycin, ritonavir, lopinavir/ritonavir, Doxycycline, Minocycline, tetracycline。
- Used medication with interaction with ivabradine: voriconazole, posaconazole, fluconazole, Ombitasvir, Dasabuvir, Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenobarbital, Phenytoin, Rifampicin
- Cardiogenic shock.
- History of symptomatic bradycardia.
- Renal insufficiency:eGFR<30 ml/min/1.73m2
- Pregnancy
- Heart failure due to congenital heart
- Severe hypotension(<90/50mmHg)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Ivabradine as a Treatment Modality for Both Rate Control and Heart Failure Medication in Patient With Both Persistent Atrial Fibrillation and Heart Failure With Reduce and Mid-range Ejection Fraction
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
- Being tested
- Ivabradine 5 mg [Corlanor], Digoxin 0.25 mg
- Medical subject headings
- Atrial Fibrillation, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivabradine 5 mg [Corlanor]Drug
Starting dose: Ivabradine 2.5mg twice daily (BID) Max Dose: Ivabradine 7.5 mg twice daily (BID)
Digoxin 0.25 mgDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Experimental | 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). Receives: Drug: Ivabradine 5 mg [Corlanor] |
| Digoxin | Active comparator | 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). Receives: Drug: Digoxin 0.25 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate change
To compare Heart Rate change monitored from 24 hr ECG. Test will be performed at Baseline (screening phase, 4 weeks time between screening/Informed consent and Randomization visit) and treatment completion (Visit 5/Week 16). Total treatment phase is 16 weeks.
Measured: 24 hr ECG test will be performed at Screening phase and End of Treatment visit(Visit5/Week 16).
6 minute walk test change
To compare 6 minute walking test walking distance change between Randomization visit(Visit 1/Week 0) and treatment completion(Visit 5/Week 16). Total Treatment phase is 16 weeks.
Measured: Test will be performed at Randomization visit (V1/Week0) and treatment completion (Visit 5/Week 16).
N-terminal pro-brain natriuretic peptide(NT-Pro BNP) change
To compare NT-Pro BNP change from blood sample collected at Baseline (screening phase, 4 weeks time between screening/informed consent and Randomization visit) and treatment completion (Visit 5/Week 16). Total treatment phase is 16 weeks.
Measured: Blood sample will be collected at Screening phase and End of Treatment visit(Visit5/Week 16).
1-10 Borg Rating of Perceived Exertion Scale change
To compare 1-10 Borg Rating of Perceived Exertion Scale change between Randomization visit (Visit1/Week0) and treatment completion (Visit 5/Week 16). Total Treatment phase is 16 weeks. The number 1-10 Borg Rating of Perceived Exertion Scale will be obtained pre and post 6 minutes walk test. The value of 1-10 Borg Rating of Perceived Exertion Scale pre 6 minutes walking test will be compared between Randomization visit (Visit1/Week0) and treatment completion (Visit 5/Week 16), and the same type of comparison will be performed for 1-10 Borg Rating of Perceived Exertion Scale values post 6 minute walk test. Rating score is as below: 0=Rest, 1=really easy, 2=easy, 3=moderate, 4=sort of hard, 5=hard, 6= between 5 and 7, 7=really hard, 8=between 7 and 9, 9=really really hard, 10=Maximal: just like my hardest race. Decrease in score value compared between Randomization visit (Visit1/Week0) and treatment completion (Visit 5/Week 16) represents better outcome.
Measured: Borg's score will be tested at Randomization visit (V1/Week0) and treatment completion (Visit 5/Week 16).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2020
- Study start26 Aug 2018
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chun-Yao Huang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Chun-Yao Huang, Taipei Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04308031
- Sponsor's protocol ID
- N201801089
- Status last verified
- Mar 2020
- First submitted
- 9 May 2019
- Last updated
- 13 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Ivabradine as a Treatment Modality for Both Rate Control and Heart Failure Medication in Patient With Both Persistent Atrial Fibrillation and Heart Failure With Reduce and Mid-range Ejection Fraction
- ClinicalTrials.gov ID
- NCT04308031
- Acronym / sponsor ID
- N201801089
- Conditions
- Atrial Fibrillation, Ivabradine, Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Chun-Yao HuangUniversity, hospital or other
- Study start
- 26 Aug 2018 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 13 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Experimental | Drug: Ivabradine 5 mg [Corlanor]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). |
| Digoxin | Active comparator | Drug: Digoxin 0.25 mgSubject 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). |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- The patient with persistent or permanent atrial fibrillation(24hr ECG) with HFrEF and HFmrEF.
- 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.
- Stable heart rhythm medication.(no change of medication in recently one week)
- Age 20 to 90 years old.
- The subject must be an adult who can read himself/herself and walk independently.
Key exclusion criteria (8 listed)
- Used medication with interaction with digoxin : Clarithromycin, Erythromycin, Azithromycin, ritonavir, lopinavir/ritonavir, Doxycycline, Minocycline, tetracycline。
- Used medication with interaction with ivabradine: voriconazole, posaconazole, fluconazole, Ombitasvir, Dasabuvir, Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenobarbital, Phenytoin, Rifampicin
- Cardiogenic shock.
- History of symptomatic bradycardia.
- Renal insufficiency:eGFR<30 ml/min/1.73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivabradine 5 mg [Corlanor]Starting dose: Ivabradine 2.5mg twice daily (BID) Max Dose: Ivabradine 7.5 mg twice daily (BID) | Drug | Ivabradine |
| Digoxin 0.25 mgStarting 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) | Drug | Digoxin |
Primary outcome
Heart rate change
Time frame: 24 hr ECG test will be performed at Screening phase and End of Treatment visit(Visit5/Week 16).
To compare Heart Rate change monitored from 24 hr ECG. Test will be performed at Baseline (screening phase, 4 weeks time between screening/Informed consent and Randomization visit) and treatment completion (Visit 5/Week 16). Total treatment phase is 16 weeks.
6 minute walk test change
Time frame: Test will be performed at Randomization visit (V1/Week0) and treatment completion (Visit 5/Week 16).
To compare 6 minute walking test walking distance change between Randomization visit(Visit 1/Week 0) and treatment completion(Visit 5/Week 16). Total Treatment phase is 16 weeks.
N-terminal pro-brain natriuretic peptide(NT-Pro BNP) change
Time frame: Blood sample will be collected at Screening phase and End of Treatment visit(Visit5/Week 16).
To compare NT-Pro BNP change from blood sample collected at Baseline (screening phase, 4 weeks time between screening/informed consent and Randomization visit) and treatment completion (Visit 5/Week 16). Total treatment phase is 16 weeks.
1-10 Borg Rating of Perceived Exertion Scale change
Time frame: Borg's score will be tested at Randomization visit (V1/Week0) and treatment completion (Visit 5/Week 16).
To compare 1-10 Borg Rating of Perceived Exertion Scale change between Randomization visit (Visit1/Week0) and treatment completion (Visit 5/Week 16). Total Treatment phase is 16 weeks. The number 1-10 Borg Rating of Perceived Exertion Scale will be obtained pre and post 6 minutes walk test. The value of 1-10 Borg Rating of Perceived Exertion Scale pre 6 minutes walking test will be compared between Randomization visit (Visit1/Week0) and treatment completion (Visit 5/Week 16), and the same type of comparison will be performed for 1-10 Borg Rating of Perceived Exertion Scale values post 6 minute walk test. Rating score is as below: 0=Rest, 1=really easy, 2=easy, 3=moderate, 4=sort of hard, 5=hard, 6= between 5 and 7, 7=really hard, 8=between 7 and 9, 9=really really hard, 10=Maximal: just like my hardest race. Decrease in score value compared between Randomization visit (Visit1/Week0) and treatment completion (Visit 5/Week 16) represents better outcome.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivabradine 5 mg [Corlanor] and Digoxin 0.25 mg in people with Atrial Fibrillation and Ivabradine, run by Chun-Yao Huang at 1 site in Taiwan.
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 5 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 13 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
Results are not available in the source record.
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 change (time frame: 24 hr ECG test will be performed at Screening phase and End of Treatment visit(Visit5/Week 16).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2020.