Effect of Targeting Left Ventricular Lead Position on the Rate of Response to Cardiac Resynchronization Therapy. (INCREMENTAL)

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Identifying & optimizing strategies to reduce the burden of heart failure is vital. Despite advances in pharmacotherapy, patients with heart failure are at high risk for death & hospitalization. Cardiac resynchronization therapy (CRT) synchronizes ventricular mechanical activity, improves cardiac output & reduces HF symptoms. However, ~50% of patients do not clearly respond to CRT. Sub-optimal placement of the LV pacing lead appears to be an important reason for non-response.

This study will assess whether targeted LV lead placement will result in an increased probability of CRT response at 52 weeks vs. usual (lateral wall) lead placement.

Condition or disease	Intervention/treatment	Phase
Heart Failure, Congestive; Cardiac Pacing, Artificial; Defibrillators	Procedure: A; Procedure: B	Phase 2; Phase 3

Detailed Description:

Background. Identifying & optimizing strategies to reduce the burden of heart failure (HF) is vital. Despite advances in pharmacotherapy, patients with HF are at high risk for death & hospitalization. Over 25% of patients with systolic HF have dyssynchronous ventricular contraction that results in paradoxical septal motion, further impairing left ventricular (LV) function & HF progression. Cardiac resynchronization therapy (CRT) synchronizes ventricular mechanical activity, improves cardiac output & reduces HF symptoms. However, ~50% of patients do not clearly respond to CRT. Sub-optimal placement of the LV pacing lead appears to be an important reason for non-response.

Screening. Mechanical synchrony is vitally important in optimizing CRT response. Patients will be pre-screened with echocardiograms (echo) & CRT provided to only those with dyssynchrony. The predicted rate of CRT response in patients pre-screened for dyssynchrony is estimated at 65%.

CRT response. The combined use of a valid & simple measure of functional capacity with a reproducible measure of LV volume is optimal in identifying CRT responders. These outcomes will be assessed using the Specific Activity Scale & radionuclide angiography (RNA), respectively.

Primary hypothesis. Targeted LV lead placement will result in an increased probability of CRT response at 52 weeks vs. usual (lateral wall) lead placement. CRT response will be defined as ≥ 10% relative reduction in LV end systolic volume & ≥ 1 Specific Activity Scale class improvement.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	96 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Investigating Non-response to Cardiac Resynchronization: Evaluation of Methods to Eliminate Non-response & Target Appropriate Lead Location (INCREMENTAL).
Study Start Date :	March 2011
Actual Primary Completion Date :	April 2014
Actual Study Completion Date :	November 2015

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: A; Targeted LV lead placement	Procedure: A; LV lead placement in region of latest mechanical velocity (tissue doppler)
Active Comparator: B; Usual LV lead placement	Procedure: B; LV lead placement in standard (lateral / posterolateral) position.

Outcome Measures

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Primary Outcome Measures :

1. Change in end systolic volume plus reduction in symptoms [ Time Frame: over 12 months ]

Secondary Outcome Measures :

1. Minnesota Living with Heart Failure score. [ Time Frame: Change over 12 months ]
2. Short form thirty six score. [ Time Frame: Change over 12 months ]
3. Specific Activity Scale score. [ Time Frame: Change over 12 months ]
4. New York Heart Association class. [ Time Frame: Change over 12 months ]
5. Six minute walk distance. [ Time Frame: Change over 12 months ]
6. LV volumes. [ Time Frame: Change over 12 months ]
7. N-terminal pro-B-type natriuretic peptide. [ Time Frame: Change over 12 months ]
8. Mortality [ Time Frame: Study duration ]
9. Hospitalization [ Time Frame: Study duration ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• LV EF ≤ 0.40 measured within 3 months of enrollment,
• SAS class 3 or 4 symptoms indicative of moderate to severe functional capacity limitation due to heart failure within 1 month of enrollment.
• Confirmed dyssynchrony on screening echo (1.1.9), &
• On stable doses of ACE inhibitor or angiotensin II blocker & a beta-blocker for ≥ 2 months unless medically contra-indicated.
• Controlled heart rate if in permanent AF (resting <70 & maximal <120).

Exclusion Criteria:

• Unable or unwilling to provide informed consent,
• Medical condition other than heart failure likely to cause death < 1 year,
• Cardiac transplant planned within 6 months,
• Known contra-indication to transvenous CRT device implant (e.g., active sepsis, artificial tricuspid valve, known vascular occlusion that will prevent delivery of leads transvenously),
• Clinically significant myocardial infarction within last 2 months, or
• Coronary bypass graft surgery ≤ 2 months or coronary angioplasty ≤ 1 month

Contacts and Locations

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Locations

Canada, Alberta
Foothills Hospital
Calgary, Alberta, Canada, T2N4N1
Canada, Ontario
London Health Sciences
London, Ontario, Canada
Canada, Quebec
Quebec Heart Institute
Ste-Foy, Quebec, Canada, G1V4G5

Sponsors and Collaborators

University of Calgary

Canadian Institutes of Health Research (CIHR)

Medtronic

Hoffmann-La Roche

Cambridge Heart Inc.

Investigators

Principal Investigator:	Derek V Exner, MD, MPH	Libin Cardiovascular Institute of Alberta, University of Calgary

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Dr. Derek Exner, Professor and Canada Research Chair in Cardiovascular Clinical Trials, University of Calgary
ClinicalTrials.gov Identifier:	NCT00399594 History of Changes
Other Study ID Numbers:	CAH 70-3402
First Posted:	November 15, 2006
Last Update Posted:	November 24, 2015
Last Verified:	November 2015

Keywords provided by Dr. Derek Exner, University of Calgary:

Mechanical dyssynchrony; Biventricular pacing; Cardiac resynchronization therapy

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases