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

Phase 4

Terminated

• Conditions: Congestive Heart Failure
• Interventions: Drug: Beta blocker (carvedilol or metoprolol succinate); Procedure: CRT (cardiac resynchronization therapy)

• Registration Number: NCT00433043
• Lead Sponsor: St. Luke's-Roosevelt Hospital Center

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.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2007-02-08
• Study First Submitted QC: 2007-02-08
• Study First Posted: 2007-02-09
• Primary Completion: 2009-05
• Study Completion: 2009-05
• Status Verified: 2014-01
• Last Update Submitted: 2015-10-28
• Last Update Posted: 2015-10-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• NYHA III-IV
• QRS > 120 msec
• On medical therapy, but beta blocker dose not @ target (carvedilol 25 bid, metoprolol succinate 200 qd)

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Exclusion Criteria

• QRS < 120 msec
• On target beta blocker dose

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	CRT (cardiac resynchronization therapy)	CRT and b-blocker uptitration to target dose
1	Beta blocker (carvedilol or metoprolol succinate)	CRT and b-blocker uptitration to target dose
2	CRT (cardiac resynchronization therapy)	CRT and continuation of entry b-blocker dose to 6 month evaluation
2	Beta blocker (carvedilol or metoprolol succinate)	CRT and continuation of entry b-blocker dose to 6 month evaluation

Primary Outcome Measures

Name	Time	Method
LVESVI change in patients with CRT/ increased dose of beta-blockers vs CRT and no change in beta-blocker dose.	6 months

Secondary Outcome Measures

Name	Time	Method
Correlation of Optivol fluid measurement increases (decreased impedance) with symptomatic worsening of heart failure during beta blocker uptitration	6 months
Exercise - 6 minute walk	6 months
Ejection fraction	6 months
Remodeling	6 months
Plasma Brain natriuretic peptide (BNP) change	6 months
Optivol measurements (decreased impedance, increase volume index) correlated with the need for adjusting diuretic therapy when uptitrating beta blocker dose	12 months
QOL - NYHA, Minnesota LWHFQ, Symptom Assessment Questionnaire	6 months
LVEDVI	6 months
HF Hospitalizations/ Mortality	6 months
Comparison of LVESVI changes based on initial beta-blocker dose	6 months
12 month comparison after Group 2 has been uptitrated.	12 months
Evaluation of LVESVI in patients who actually achieve target dose	6 months
Functional improvements	6 months

Trial Locations

Locations (3)

St. Lukes Roosevelt Hospital; 🇺🇸 New York, New York, United States

Jefferson Medical College; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Rochester; 🇺🇸 Rochester, New York, United States