BOAT: Beta Blocker Uptitration With OptiVol After Cardiac Resynchronization Therapy (CRT) - Full Text View

Sponsor:	St. Luke's-Roosevelt Hospital Center
Collaborator:	Medtronic
Information provided by:	St. Luke's-Roosevelt Hospital Center
ClinicalTrials.gov Identifier:	NCT00433043

Purpose

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).

Condition	Intervention	Phase
Congestive Heart Failure	Drug: Beta blocker (carvedilol or metoprolol succinate) Procedure: CRT (cardiac resynchronization therapy)	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Beta-Blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure

Drug Information available for: Metoprolol Metoprolol Tartrate Carvedilol Succinic acid Metoprolol succinate Metoprolol fumarate

U.S. FDA Resources

Further study details as provided by St. Luke's-Roosevelt Hospital Center:

Primary Outcome Measures:

LVESVI change in patients with CRT/ increased dose of beta-blockers vs CRT and no change in beta-blocker dose. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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

Estimated Enrollment:	60
Study Start Date:	January 2007
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 CRT and b-blocker uptitration to target dose	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
Active Comparator: 2 CRT and continuation of entry b-blocker dose to 6 month evaluation	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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433043

Locations

United States, New York
St. Lukes Roosevelt Hospital
New York, New York, United States, 10019
University of Rochester
Rochester, New York, United States, 14642
United States, Pennsylvania
Jefferson Medical College
Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

St. Luke's-Roosevelt Hospital Center

Medtronic

Investigators

Principal Investigator:

Marrick L Kukin, MD

St. Luke's Roosevelt Hospitals

More Information

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.

Responsible Party:	Marrick Kukin, MD, St. Luke's Roosevelt Hospital
ClinicalTrials.gov Identifier:	NCT00433043 History of Changes
Other Study ID Numbers:	06-107
Study First Received:	February 8, 2007
Last Updated:	May 5, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by St. Luke's-Roosevelt Hospital Center:

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)

Additional relevant MeSH terms:

Heart Failure
Heart Diseases
Cardiovascular Diseases
Adrenergic beta-Antagonists
Metoprolol
Metoprolol succinate
Carvedilol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists

ClinicalTrials.gov processed this record on February 09, 2012