BOAT: Beta Blocker Uptitration With OptiVol After CRT.

Condition(s) targeted: Congestive Heart Failure

Intervention: Beta blocker (carvedilol or metoprolol succinate) (Drug); CRT (cardiac resynchronization therapy) (Device)

Phase: Phase 4

Status: Recruiting

Sponsored by: St. Luke's-Roosevelt Hospital Center

Official(s) and/or principal investigator(s):
Marrick L Kukin, MD, Principal Investigator, Affiliation: St. Luke's Roosevelt Hospitals

Overall contact:
Marrick L Kukin, MD, Phone: 212 492-5546, Email: mkukin@chpnet.org

Many heart failure patients are unable to reach target beta blocker doses. This study will address whether cardiac resynchronization therapy (CRT) will enable uptitration of beta-blockers to target doses and whether it will favorably affect remodeling by reducing left ventricular end systolic volume (LVESV), with measurable clinical benefit, beyond CRT alone (without changes in beta-blocker dose).

Official title: Beta-Blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System

Study design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: LVESVI change in patients with CRT/ increased dose of beta-blockers vs CRT and no change in beta-blocker dose.

Secondary outcome:

Correlation of Optivol fluid measurement increases (decreased impedance) with symptomatic worsening of heart failure during beta blocker uptitration

Optivol measurements (decreased impedance, increase volume index) correlated with the need for adjusting diuretic therapy when uptitrating beta blocker dose

Functional improvements

Exercise - 6 minute walk

QOL - NYHA, Minnesota LWHFQ, Symptom Assessment Questionnaire

Ejection fraction

LVEDVI

Remodeling

HF Hospitalizations/ Mortality

Evaluation of LVESVI in patients who actually achieve target dose

Comparison of LVESVI changes based on initial beta-blocker dose

Plasma Brain natriuretic peptide (BNP) change

12 month comparison after Group 2 has been uptitrated.

Detailed description: Beta blockers have been proven to have benefit in heart failure (HF) patients with regard to morbidity and mortality. However, initiation and uptitration remains a challenge in many patients. Worsening of heart failure, symptomatic hypotension and symptomatic bradycardia all limit up-titration to the target doses that have been shown to have mortality benefits (carvedilol [Coreg] 25 mg bid, metoprolol succinate [Toprol-XL] 200 mg qd) in the large clinical trials (COPERNICUS, MERIT-HF).

It is debated whether the benefit of beta-blockade is solely due to heart rate reduction or more broadly from the cardiac, central and peripheral effects of blocking sympathetic activity. Clearly, there is a remodeling effect on the dilated ventricle. Furthermore, patients with heart rates of 64 bpm or less are rarely begun on beta-blocker therapy. It is not known whether these patients should be given a pacemaker in order to then safely initiate beta-blocker therapy.

It is also clear that isolated right ventricular pacing can have deleterious effects on ventricular dysynchrony and symptomatic heart failure despite medical therapy. Biventricular pacing (BIVPM), also known as cardiac resynchronization therapy (CRT), is the pacing mode of choice for patients with wide QRS complexes and symptomatic HF.

It is hypothesized that CRT therapy allows for increased Beta - blocker dose (or initiation of

beta-blocker in patients previously intolerant) with improved NYHA, ejection fraction, and remodeling effects. The synergy between two established heart failure therapies requires further evaluation in a prospective randomized trial.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- NYHA III-IV,

- QRS > 120 msec,

- On medical therapy, but beta blocker dose not @ target (carvedilol 25 bid, metoprolol

succinate 200 qd)

Exclusion Criteria:

- QRS< 120 msec,

- On target beta blocker dose

Marrick L Kukin, MD, Phone: 212 492-5546, Email: mkukin@chpnet.org

University of Rochester, Rochester, New York 14642, United States; Not yet recruiting
Thomas Rocco, MD, Phone: 585-341-6780, Email: thomas_rocco@urmc.rochester.edu
Janice Spence, Phone: (585) 275-1673, Email: janice_spence@URMC.rochester.edu
Thomas Rocco, MD, Principal Investigator

St. Lukes Roosevelt Hospital, New York, New York 10019, United States; Recruiting
Marrick L Kukin, MD, Phone: 212-492-5546, Email: mkukin@chpnet.org
Cathleen B Varley, NP, Phone: 212 492-5546, Email: cvarley@chpnet.org
Marrick L Kukin, MD, Principal Investigator

Jefferson Medical College, Philadelphia, Pennsylvania 19107, United States; Recruiting
David Whellan, MD, Phone: 215-955-2007, Email: david.whellan@jefferson.edu
Suzanne Adams, RN, MPH, Phone: 215 955 8848, Email: Suzanne.Adams@jefferson.edu
David Whellan, MD, Principal Investigator

Related publications:

Aranda JM Jr, Woo GW, Conti JB, Schofield RS, Conti CR, Hill JA. Use of cardiac resynchronization therapy to optimize beta-blocker therapy in patients with heart failure and prolonged QRS duration. Am J Cardiol. 2005 Apr 1;95(7):889-91.

[No authors listed] Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) Lancet. 1999 Jun 12;353(9169):2001-7.

Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL; Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8.

Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50.

Starting date: January 2007
Ending date: June 2013
Last updated: May 20, 2008