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Effect of Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Right Ventricular Pacing

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ClinicalTrials.gov Identifier: NCT01868880
Recruitment Status : Suspended (difficulties in recruiting patients)
First Posted : June 5, 2013
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Leonardo Calo, Policlinico Casilino ASL RMB

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.


Condition or disease Intervention/treatment Phase
Heart Rate Control in ICD Patients With Heart Failure Drug: Ivabradine plus beta-blocker (bisoprolol) Drug: betablocker titration Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : February 2016
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: 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)
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).

Active Comparator: beta-blocker (bisoprolol) titration
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.
Drug: betablocker titration
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.




Primary Outcome Measures :
  1. Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Number of episodes of non-sustained and sustained ventricular tachycardia and ventricular fibrillation [ Time Frame: 12 months ]
  2. Number of ICD shock-delivery for ventricular fibrillation and sustained ventricular tachycardia [ Time Frame: 12 months ]
  3. Ejection fraction decrease < 5% from baseline value [ Time Frame: 12 months ]
  4. Left Ventricular End-Systolic Volume decrease <15% from baseline value [ Time Frame: 12 months ]
  5. Heart rate variability increase (> 10%) from baseline value [ Time Frame: 12 months ]
  6. reduction of at least one NYHA Class from baseline value [ Time Frame: 12 months ]
  7. Change in Minnesota Living Heart Failure Questionnaire scores (>5) from the baseline score. [ Time Frame: 12 months ]
  8. Right ventricular pacing percentage reduction (> 10%) from baseline value [ Time Frame: 12 months ]
  9. Composite endpoint: number of cardiovascular death and hospitalization due to worsening heart failure. [ Time Frame: 12 months ]
  10. Crossover rate due to worsening heart failure [ Time Frame: 12 months ]


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Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01868880


Locations
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Italy
Polinico Casilino
Rome, Italy, 00169
Sponsors and Collaborators
Policlinico Casilino ASL RMB

Publications:
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Responsible Party: Leonardo Calo, MD, FESC, Policlinico Casilino ASL RMB
ClinicalTrials.gov Identifier: NCT01868880     History of Changes
Other Study ID Numbers: calo03
calo03 ( Other Identifier: Policlinico Casilino )
First Posted: June 5, 2013    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Adrenergic beta-Antagonists
Bisoprolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists