Ignite Creation Date:
2024-05-06 @ 1:39 AM
Last Modification Date:
2024-10-26 @ 11:07 AM
Study NCT ID:
NCT01868880
Status:
WITHDRAWN
Last Update Posted:
2020-03-13
First Post:
2013-05-09
Brief Title:
Effect of Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Right Ventricular Pacing
Sponsor:
Policlinico Casilino ASL RMB
Organization:
Policlinico Casilino ASL RMB
Study Overview
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
Status:
WITHDRAWN
Status Verified Date:
2020-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
difficulties in recruiting patients
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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-defibrillatorICD patients particularly in those with preexistent left ventricular dysfunction12 Cumulative RV pacing 2 and ejection fraction EF 40 are independent predictors for Ventricular TachycardiaVTVentricular Fibrillation VF occurrence in ICD patients3 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 contractility4 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-blockerbisoprolol 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 125 or 25 mg After four weeks of treatment ivabradine will be eventually lowered up to 25 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 125-25 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
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-defibrillatorICD patients particularly in those with preexistent left ventricular dysfunction12 Cumulative RV pacing 2 and ejection fraction EF 40 are independent predictors for Ventricular TachycardiaVTVentricular Fibrillation VF occurrence in ICD patients3 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 contractility4 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-blockerbisoprolol 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 125 or 25 mg After four weeks of treatment ivabradine will be eventually lowered up to 25 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 125-25 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| calo03 | OTHER | Policlinico Casilino | None |