Clinical trial NCT00433043: BOAT: Beta Blocker Uptitration With OptiVol After Cardiac Resynchronization Therapy (CRT)
Official title: Beta-blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Congestive Heart Failure
Keywords: Heart Failure
Beta blockers
Resynchronization
Congestive Heart Failure, NYHA III-IV
Candidate for BIVPM
Not on Target Dose (Coreg 25 Bid or Toprol XL 200 qd)
Lead sponsor: St. Luke's-Roosevelt Hospital Center
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2007-02-09
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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 dyssynchrony 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.

Eligibility 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

Primary outcomes:
measure: LVESVI change in patients with CRT/ increased dose of beta-blockers vs CRT and no change in beta-blocker dose.
timeFrame: 6 months
Secondary outcomes:
measure: Correlation of Optivol fluid measurement increases (decreased impedance) with symptomatic worsening of heart failure during beta blocker uptitration
timeFrame: 6 months
measure: Optivol measurements (decreased impedance, increase volume index) correlated with the need for adjusting diuretic therapy when uptitrating beta blocker dose
timeFrame: 12 months
measure: Functional improvements
timeFrame: 6 months
measure: Exercise - 6 minute walk
timeFrame: 6 months
measure: QOL - NYHA, Minnesota LWHFQ, Symptom Assessment Questionnaire
timeFrame: 6 months
measure: Ejection fraction
timeFrame: 6 months
measure: LVEDVI
timeFrame: 6 months
measure: Remodeling
timeFrame: 6 months
measure: HF Hospitalizations/ Mortality
timeFrame: 6 months
measure: Evaluation of LVESVI in patients who actually achieve target dose
timeFrame: 6 months
measure: Comparison of LVESVI changes based on initial beta-blocker dose
timeFrame: 6 months
measure: Plasma Brain natriuretic peptide (BNP) change
timeFrame: 6 months
measure: 12 month comparison after Group 2 has been uptitrated.
timeFrame: 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: St. Lukes Roosevelt Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Philadelphia
country: United States
facility: Jefferson Medical College
state: Pennsylvania
Study officials:
affiliation: St. Luke's Roosevelt Hospitals
name: Marrick L Kukin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/j.amjcard.2004.12.023.
citation: 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.
citation: 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. doi: 10.1056/NEJM200105313442201.
citation: 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. doi: 10.1056/NEJMoa032423.