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

This study has been terminated.
(Insufficient enrollment)
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
St. Luke's-Roosevelt Hospital Center
ClinicalTrials.gov Identifier:
NCT00433043
First received: February 8, 2007
Last updated: April 9, 2014
Last verified: February 2014
  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 4

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:


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 ]

Enrollment: 2
Study Start Date: January 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (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:
Responsible Party: St. Luke's-Roosevelt Hospital Center
ClinicalTrials.gov Identifier: NCT00433043     History of Changes
Other Study ID Numbers: 06-107
Study First Received: February 8, 2007
Last Updated: April 9, 2014
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 April 17, 2014