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

NCT01868880 | Withdrawn Phase 4

• 1 other identifier: calo03
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Rate Control in ICD Patients With Heart Failure

Outcome Measures

Primary Outcomes (1)

• Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.

  12 months

Secondary Outcomes (10)

• Number of episodes of non-sustained and sustained ventricular tachycardia and ventricular fibrillation

  12 months

• Number of ICD shock-delivery for ventricular fibrillation and sustained ventricular tachycardia

  12 months

• Ejection fraction decrease < 5% from baseline value

  12 months

• Left Ventricular End-Systolic Volume decrease <15% from baseline value

  12 months

• Heart rate variability increase (> 10%) from baseline value

  12 months

Study Arms (2)

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).

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.

Drug: betablocker titration

Interventions

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).

ivabradine plus beta-blocker(bisoprolol)

betablocker titration DRUG

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.

beta-blocker (bisoprolol) titration

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Policlinico Casilino ASL RMB: lead

Study Sites (1)

Polinico Casilino

Rome, 00169, Italy

Location

Related Publications (3)

• 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.

  PMID: 16051118 BACKGROUND

• Smit 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.

  PMID: 17161779 BACKGROUND

• Borer 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.

  PMID: 18806523 BACKGROUND

MeSH Terms

Interventions

Ivabradine; Adrenergic beta-Antagonists; Bisoprolol

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FESC

Study Record Dates

• First Submitted: May 9, 2013
• First Posted: June 5, 2013
• Study Start: February 1, 2016
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: March 13, 2020

Record last verified: 2020-03

Locations

IT (1)