Official Title: “Beta-Blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2012

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.

Intervention(s) in this Clinical Trial

• 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.
• Device: CRT (cardiac resynchronization therapy)
  • Both arms

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • CRT and b-blocker uptitration to target dose
• Active Comparator: 2
  • CRT and continutation of entry b-blocker dose to 6 month evaluation

Primary 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
    Safety Issue?: No

Secondary Measures

• Correlation of Optivol fluid measurement increases (decreased impedance) with symptomatic worsening of heart failure during beta blocker uptitration
  • Time Frame: 6 months
    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
    Safety Issue?: No
• Functional improvements
  • Time Frame: 6 months
    Safety Issue?: No
• Exercise - 6 minute walk
  • Time Frame: 6 months
    Safety Issue?: No
• QOL - NYHA, Minnesota LWHFQ, Symptom Assessment Questionnaire
  • Time Frame: 6 months
    Safety Issue?: No
• Ejection fraction
  • Time Frame: 6 months
    Safety Issue?: No
• LVEDVI
  • Time Frame: 6 months
    Safety Issue?: No
• Remodeling
  • Time Frame: 6 months
    Safety Issue?: No
• HF Hospitalizations/ Mortality
  • Time Frame: 6 months
    Safety Issue?: Yes
• Evaluation of LVESVI in patients who actually achieve target dose
  • Time Frame: 6 months
    Safety Issue?: No
• Comparison of LVESVI changes based on initial beta-blocker dose
  • Time Frame: 6 months
    Safety Issue?: No
• Plasma Brain natriuretic peptide (BNP) change
  • Time Frame: 6 months
    Safety Issue?: No
• 12 month comparison after Group 2 has been uptitrated.
  • Time Frame: 12 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: St. Luke's-Roosevelt Hospital Center

Overall Clinical Trial Officials and Contacts

Marrick L Kukin, MD Principal Investigator St. Luke's Roosevelt Hospitals  

Overall Contact: Marrick L Kukin, MD 212 492-5546 mkukin@chpnet.org

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00433043

Study ID Number: 06-107

ClinicalTrials.gov Identifier: NCT00433043

Health Authority: United States: Institutional Review Board