BOAT: Beta Blocker Uptitration With OptiVol After Cardiac Resynchronization Therapy (CRT)

Congestive Heart Failure Clinical Trial

Official title:

Beta-blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00433043
• Other study ID #: 06-107
• Status: Terminated
• Phase: Phase 4
• First received: February 8, 2007
• Last updated: October 28, 2015
• Start date: January 2007
• Est. completion date: May 2009

Study information

• Verified date: January 2014
• Source: St. Luke's-Roosevelt Hospital Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Beta blocker (carvedilol or metoprolol succinate)
Both groups get CRT. Group 1 is uptitrated to target dose beta blocker after CRT. Group 2 maintains their b-blocker dose from study entry.

Procedure:
• CRT (cardiac resynchronization therapy)
Both arms

Locations

Country	Name	City	State
United States	St. Lukes Roosevelt Hospital	New York	New York
United States	Jefferson Medical College	Philadelphia	Pennsylvania
United States	University of Rochester	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
St. Luke's-Roosevelt Hospital Center	Medtronic

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LVESVI change in patients with CRT/ increased dose of beta-blockers vs CRT and no change in beta-blocker dose.		6 months	No
Secondary	Correlation of Optivol fluid measurement increases (decreased impedance) with symptomatic worsening of heart failure during beta blocker uptitration		6 months	No
Secondary	Optivol measurements (decreased impedance, increase volume index) correlated with the need for adjusting diuretic therapy when uptitrating beta blocker dose		12 months	No
Secondary	Functional improvements		6 months	No
Secondary	Exercise - 6 minute walk		6 months	No
Secondary	QOL - NYHA, Minnesota LWHFQ, Symptom Assessment Questionnaire		6 months	No
Secondary	Ejection fraction		6 months	No
Secondary	LVEDVI		6 months	No
Secondary	Remodeling		6 months	No
Secondary	HF Hospitalizations/ Mortality		6 months	Yes
Secondary	Evaluation of LVESVI in patients who actually achieve target dose		6 months	No
Secondary	Comparison of LVESVI changes based on initial beta-blocker dose		6 months	No
Secondary	Plasma Brain natriuretic peptide (BNP) change		6 months	No
Secondary	12 month comparison after Group 2 has been uptitrated.		12 months	No