Heart Rate Control in ICD Patients With Heart FailurePhase 4NCT01868880
Effect of Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Right Ventricular Pacing
A Phase 4 study testing Ivabradine plus beta-blocker (bisoprolol) and betablocker titration in people with Heart Rate Control in ICD Patients With Heart Failure, run by Policlinico Casilino ASL RMB at 1 site in Italy.
Trial summary
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD… Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Heart Rate Control in ICD Patients With Heart Failure
- What is being tested?
- Ivabradine plus beta-blocker (bisoprolol) and betablocker titration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2016to Dec 2023
- Phase
- Phase 4
- 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 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Patients with stable chronic heart failure implanted with mono-cameral or bicameral ICD with a home monitoring remote control.
- Moderate to severe left ventricular dysfunction (FE ≤ 40%).
- Any cause of heart failure was allowed apart congenital heart disease.
- Bicameral ICD programmed in DDD or AAI/DDD with AV interval < 300 msec.
- Rest ECG heart rate ≥70 bpm;
- Sinus rhythm.
- In therapy with low-dose of beta-blocker (bisoprolol 1,25-2,5 mg) and with the maximum dose tolerated of angiotensin-converting enzyme inhibitor or blockade of angiotensin II receptor, mineralocorticoid antagonist, antiplatelet and lipid-lowering therapy, unless contraindicated.
Who cannot join
- Inability of providing informed consent;
- Age < 18 years.
- State of pregnancy or lactation.
- Recent (<2 months) myocardial infarction;
- Contraindications to beta-blockers and ivabradine;
- Rest ECG heart rate < 70 bpm;
- No sinus rhythm.
- Administration of non-dihydropyridinic calcium channels antagonists, digitalis, class I antiarrhythmic drugs, strong inhibitors of cytochrome P450 3A4 at the time of enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Heart Rate Control Using Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Ventricular Pacing in Heart Failure Patients With an Implanted Cardioverter Defibrillator.
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD recipients HF patients with moderate to severe left ventricular dysfunction (FE ≤ 40%) and an heart rate ≥ 70 bpm in sinus rhythm over a 12-months follow up.
Besides the investigators want to assess if the combination of ivabradine to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) may determine a lower degree of left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart failure patients.
Read the detailed description
Background
High heart rate (HR) represent per se a risk factor for cardiovascular mortality and heart failure (HF) progression, despite optimal HF therapy. Beta-blockers remain the therapy of choice in all patients with systolic HF, but they may worsen atrioventricular (AV) conduction and increase right ventricular (RV) pacing percentage. Several studies have demonstrated detrimental effects of RV pacing on cardiac function. Percent RV pacing > 40-50% is an independent predictor of death and hospitalization for HF in implantable cardioverter-defibrillator(ICD) patients, particularly in those with preexistent left ventricular dysfunction.1,2 Cumulative RV pacing > 2% and ejection fraction (EF) < 40% are independent predictors for Ventricular Tachycardia(VT)/Ventricular Fibrillation (VF) occurrence in ICD patients.3 Therefore reduction of cumulative RV pacing as far as possible should be achieved in ICD patients. Ivabradine is a specific inhibitor of the If current of the sinus node, that induces a selective and dose dependent HR reduction; it is a pure HR lowering agent without effects on AV conduction or contractility.4 In HF patients implanted with an ICD ivabradine could act as an heart rate control drug in combination with a beta-blocker without increase right ventricular (RV) pacing percentage and may be an option to reduce left-ventricular dysfunction progression and ventricular arrhythmias burden and appropriate ICD therapy.
Aim
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD recipients HF patients with moderate to severe left ventricular dysfunction (FE ≤ 40%) and an heart rate ≥70 bpm in sinus rhythm over a 12-months follow up.
Besides we want to assess if the combination of ivabradine to a low-dose of beta-blocker (bisoprolol) versus titration of beta-blocker (bisoprolol) may determine a lower degree of left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart failure patients.
Endpoints of the study
Primary endpoints:
Right ventricular pacing percentage increase > 50% or Cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.
Secondary endpoints:
Ejection fraction decrease < 5% and Left Ventricular End-Systolic Volume decrease <15%.
Ventricular arrhythmias and ICD appropriate therapy reduction. Heart rate variability improvement NYHA Classification improvement Minnesota Living With Heart Failure Questionnaire (MLHFQ) total score reduction.
Right ventricular pacing percentage. Composite endpoint: cardiovascular death and hospitalization due to worsening heart failure.
Crossover rate due to worsening heart failure
Study protocol:
Baseline assessment:
Clinical visit: demographic data, risk factors for cardiovascular disease, primary cause of heart failure, NYHA class, comorbidities, echocardiographic parameters, drug therapy, cardiovascular hospitalizations in the last year.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Blood pressure measurement; Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data); Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); MLHFQ
Assignment of consecutive patients to treatment with ivabradine plus beta-blocker(bisoprolol) or beta-blocker (bisoprolol) titration. Mean Heart Rate Target is 55-70 bpm for both groups.
Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness).
Beta blocker Bisoprolol will be up-titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose.
Patients are controlled in office follow-up visits after 3, 6 and 12 months, in addition to a Remote Monitoring program for clinical data and trend reviewing at least every 15 days or as soon as possible whenever a Remote Monitoring alert notification is received. Besides every 15 days patients will receive a telephone contact in order to evaluate their clinical state and to uptitrate the beta blocker therapy based on mean heart rate detected trough remote control of the ICD.
Three months in-office follow-up:
Clinical visit: symptoms, NYHA class, drug therapy, cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Blood pressure measurement; Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data) .
Six months in office follow-up:
Clinical visit: NYHA class, comorbidities, echocardiographic parameters, drug therapy, cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data).
MLHFQ
One year in office follow-up:
Clinical visit: NYHA class, comorbidities, echocardiographic parameters, drug therapy, cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data).
Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); MLHFQ
- Being tested
- Ivabradine plus beta-blocker (bisoprolol), betablocker titration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivabradine plus beta-blocker (bisoprolol)Drug
Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness).
betablocker titrationDrug
Beta blocker Bisoprolol will be up-titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose.
| Study group | Role | What they receive |
|---|---|---|
| ivabradine plus beta-blocker(bisoprolol) | Experimental | Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness). Receives: Drug: Ivabradine plus beta-blocker (bisoprolol) |
| beta-blocker (bisoprolol) titration | Active comparator | Beta blocker Bisoprolol will be titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose. Receives: Drug: betablocker titration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.
Measured: 12 months
Secondary outcomes (10)
Number of episodes of non-sustained and sustained ventricular tachycardia and ventricular fibrillation
Measured: 12 months
Number of ICD shock-delivery for ventricular fibrillation and sustained ventricular tachycardia
Measured: 12 months
Ejection fraction decrease < 5% from baseline value
Measured: 12 months
Left Ventricular End-Systolic Volume decrease <15% from baseline value
Measured: 12 months
Heart rate variability increase (> 10%) from baseline value
Measured: 12 months
reduction of at least one NYHA Class from baseline value
Measured: 12 months
Change in Minnesota Living Heart Failure Questionnaire scores (>5) from the baseline score.
Measured: 12 months
Right ventricular pacing percentage reduction (> 10%) from baseline value
Measured: 12 months
Composite endpoint: number of cardiovascular death and hospitalization due to worsening heart failure.
Measured: 12 months
Crossover rate due to worsening heart failure
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2013 (estimated)
- Study startFeb 2016
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Why it stopped: difficulties in recruiting patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Heart Rate Control in ICD Patients With Heart FailureStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Policlinico Casilino ASL RMB
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leonardo Calò, MD, Policlinico Casilino ASL RMB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01868880
- Sponsor's protocol ID
- calo03
- Other IDs
- calo03
- Status last verified
- Mar 2020
- First submitted
- 9 May 2013
- Last updated
- 13 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Sharma AD, Rizo-Patron C, Hallstrom AP, O'Neill GP, Rothbart S, Martins JB, Roelke M, Steinberg JS, Greene HL; DAVID Investigators. Percent right ventricular pacing predicts outcomes in the DAVID trial. Heart Rhythm. 2005 Aug;2(8):830-4. doi: 10.1016/j.hrthm.2005.05.015.
PubMed 16051118Smit MD, Van Dessel PF, Nieuwland W, Wiesfeld AC, Tan ES, Anthonio RL, Van Erven L, Van Veldhuisen DJ, Van Gelder IC. Right ventricular pacing and the risk of heart failure in implantable cardioverter-defibrillator patients. Heart Rhythm. 2006 Dec;3(12):1397-403. doi: 10.1016/j.hrthm.2006.08.006. Epub 2006 Aug 10.
PubMed 17161779Borer JS, Le Heuzey JY. Characterization of the heart rate-lowering action of ivabradine, a selective I(f) current inhibitor. Am J Ther. 2008 Sep-Oct;15(5):461-73. doi: 10.1097/MJT.0b013e3181758855.
PubMed 18806523
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
- Effect of Heart Rate Control Using Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Ventricular Pacing in Heart Failure Patients With an Implanted Cardioverter Defibrillator.
- ClinicalTrials.gov ID
- NCT01868880
- Acronym / sponsor ID
- calo03
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: difficulties in recruiting patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Policlinico Casilino ASL RMBUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 5 Jun 2013 (estimated)
- 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.
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD recipients HF patients with moderate to severe left ventricular dysfunction (FE ≤ 40%) and an heart rate ≥ 70 bpm in sinus rhythm over a 12-months follow up.
Besides the investigators want to assess if the combination of ivabradine to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) may determine a lower degree of left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart failure patients.
Detailed description
Background
High heart rate (HR) represent per se a risk factor for cardiovascular mortality and heart failure (HF) progression, despite optimal HF therapy. Beta-blockers remain the therapy of choice in all patients with systolic HF, but they may worsen atrioventricular (AV) conduction and increase right ventricular (RV) pacing percentage. Several studies have demonstrated detrimental effects of RV pacing on cardiac function. Percent RV pacing > 40-50% is an independent predictor of death and hospitalization for HF in implantable cardioverter-defibrillator(ICD) patients, particularly in those with preexistent left ventricular dysfunction.1,2 Cumulative RV pacing > 2% and ejection fraction (EF) < 40% are independent predictors for Ventricular Tachycardia(VT)/Ventricular Fibrillation (VF) occurrence in ICD patients.3 Therefore reduction of cumulative RV pacing as far as possible should be achieved in ICD patients. Ivabradine is a specific inhibitor of the If current of the sinus node, that induces a selective and dose dependent HR reduction; it is a pure HR lowering agent without effects on AV conduction or contractility.4 In HF patients implanted with an ICD ivabradine could act as an heart rate control drug in combination with a beta-blocker without increase right ventricular (RV) pacing percentage and may be an option to reduce left-ventricular dysfunction progression and ventricular arrhythmias burden and appropriate ICD therapy.
Aim
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD recipients HF patients with moderate to severe left ventricular dysfunction (FE ≤ 40%) and an heart rate ≥70 bpm in sinus rhythm over a 12-months follow up.
Besides we want to assess if the combination of ivabradine to a low-dose of beta-blocker (bisoprolol) versus titration of beta-blocker (bisoprolol) may determine a lower degree of left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart failure patients.
Endpoints of the study
Primary endpoints:
Right ventricular pacing percentage increase > 50% or Cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.
Secondary endpoints:
Ejection fraction decrease < 5% and Left Ventricular End-Systolic Volume decrease <15%.
Ventricular arrhythmias and ICD appropriate therapy reduction. Heart rate variability improvement NYHA Classification improvement Minnesota Living With Heart Failure Questionnaire (MLHFQ) total score reduction.
Right ventricular pacing percentage. Composite endpoint: cardiovascular death and hospitalization due to worsening heart failure.
Crossover rate due to worsening heart failure
Study protocol:
Baseline assessment:
Clinical visit: demographic data, risk factors for cardiovascular disease, primary cause of heart failure, NYHA class, comorbidities, echocardiographic parameters, drug therapy, cardiovascular hospitalizations in the last year.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Blood pressure measurement; Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data); Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); MLHFQ
Assignment of consecutive patients to treatment with ivabradine plus beta-blocker(bisoprolol) or beta-blocker (bisoprolol) titration. Mean Heart Rate Target is 55-70 bpm for both groups.
Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness).
Beta blocker Bisoprolol will be up-titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose.
Patients are controlled in office follow-up visits after 3, 6 and 12 months, in addition to a Remote Monitoring program for clinical data and trend reviewing at least every 15 days or as soon as possible whenever a Remote Monitoring alert notification is received. Besides every 15 days patients will receive a telephone contact in order to evaluate their clinical state and to uptitrate the beta blocker therapy based on mean heart rate detected trough remote control of the ICD.
Three months in-office follow-up:
Clinical visit: symptoms, NYHA class, drug therapy, cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Blood pressure measurement; Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data) .
Six months in office follow-up:
Clinical visit: NYHA class, comorbidities, echocardiographic parameters, drug therapy, cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data).
MLHFQ
One year in office follow-up:
Clinical visit: NYHA class, comorbidities, echocardiographic parameters, drug therapy, cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced rhythm, QRS duration); Electronic device control (for assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic data).
Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction); MLHFQ
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ivabradine plus beta-blocker(bisoprolol) | Experimental | Drug: Ivabradine plus beta-blocker (bisoprolol)Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness). |
| beta-blocker (bisoprolol) titration | Active comparator | Drug: betablocker titrationBeta blocker Bisoprolol will be titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose. |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years.
- Patients with stable chronic heart failure implanted with mono-cameral or bicameral ICD with a home monitoring remote control.
- Moderate to severe left ventricular dysfunction (FE ≤ 40%).
- Any cause of heart failure was allowed apart congenital heart disease.
- Bicameral ICD programmed in DDD or AAI/DDD with AV interval < 300 msec.
Key exclusion criteria (8 listed)
- Inability of providing informed consent;
- Age < 18 years.
- State of pregnancy or lactation.
- Recent (<2 months) myocardial infarction;
- Contraindications to beta-blockers and ivabradine;
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 plus beta-blocker (bisoprolol)Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness). | Drug | ivabradine plus beta-blocker(bisoprolol) |
| betablocker titrationBeta blocker Bisoprolol will be up-titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose. | Drug | beta-blocker (bisoprolol) titration |
Primary outcome
Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.
Time frame: 12 months
10 secondary outcomes
Number of episodes of non-sustained and sustained ventricular tachycardia and ventricular fibrillation
Time frame: 12 months
Number of ICD shock-delivery for ventricular fibrillation and sustained ventricular tachycardia
Time frame: 12 months
Ejection fraction decrease < 5% from baseline value
Time frame: 12 months
Left Ventricular End-Systolic Volume decrease <15% from baseline value
Time frame: 12 months
Heart rate variability increase (> 10%) from baseline value
Time frame: 12 months
reduction of at least one NYHA Class from baseline value
Time frame: 12 months
Change in Minnesota Living Heart Failure Questionnaire scores (>5) from the baseline score.
Time frame: 12 months
Right ventricular pacing percentage reduction (> 10%) from baseline value
Time frame: 12 months
Composite endpoint: number of cardiovascular death and hospitalization due to worsening heart failure.
Time frame: 12 months
Crossover rate due to worsening heart failure
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2020.
- Background: PubMed 16051118Sharma AD, Rizo-Patron C, Hallstrom AP, O'Neill GP, Rothbart S, Martins JB, Roelke M, Steinberg JS, Greene HL; DAVID Investigators. Percent right ventricular pacing predicts outcomes in the DAVID trial. Heart Rhythm. 2005 Aug;2(8):830-4. doi: 10.1016/j.hrthm.2005.05.015.
- Background: PubMed 17161779Smit MD, Van Dessel PF, Nieuwland W, Wiesfeld AC, Tan ES, Anthonio RL, Van Erven L, Van Veldhuisen DJ, Van Gelder IC. Right ventricular pacing and the risk of heart failure in implantable cardioverter-defibrillator patients. Heart Rhythm. 2006 Dec;3(12):1397-403. doi: 10.1016/j.hrthm.2006.08.006. Epub 2006 Aug 10.
- Background: PubMed 18806523Borer JS, Le Heuzey JY. Characterization of the heart rate-lowering action of ivabradine, a selective I(f) current inhibitor. Am J Ther. 2008 Sep-Oct;15(5):461-73. doi: 10.1097/MJT.0b013e3181758855.
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 4 study testing Ivabradine plus beta-blocker (bisoprolol) and betablocker titration in people with Heart Rate Control in ICD Patients With Heart Failure, run by Policlinico Casilino ASL RMB at 1 site in Italy.
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 8 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: withdrawn, 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 Italy. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure. (time frame: 12 months). 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 NCT01868880, which also lists 3 linked publications.
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.