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

NCT ID: NCT00433043

Last Updated: 2015-10-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2009-05-31

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.

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

CRT and b-blocker uptitration to target dose

Group Type: ACTIVE_COMPARATOR

Beta blocker (carvedilol or metoprolol succinate)

Intervention Type: DRUG

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.

CRT (cardiac resynchronization therapy)

Intervention Type: PROCEDURE

Both arms

2

CRT and continuation of entry b-blocker dose to 6 month evaluation

Group Type: ACTIVE_COMPARATOR

Beta blocker (carvedilol or metoprolol succinate)

Intervention Type: DRUG

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.

CRT (cardiac resynchronization therapy)

Intervention Type: PROCEDURE

Both arms

Interventions

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.

Intervention Type: DRUG

CRT (cardiac resynchronization therapy)

Both arms

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

St. Luke's-Roosevelt Hospital Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marrick L Kukin, MD

Role: PRINCIPAL_INVESTIGATOR

St. Luke's Roosevelt Hospitals

Locations

St. Lukes Roosevelt Hospital

New York, New York, United States

University of Rochester

Rochester, New York, United States

Jefferson Medical College

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15781026 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10376614 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11386263 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15152059 (View on PubMed)

Other Identifiers

06-107

Identifier Type: -

Identifier Source: org_study_id