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

Heart Failure, Congestive Clinical Trial

— INCREMENTAL  

Official title:

Investigating Non-response to Cardiac Resynchronization: Evaluation of Methods to Eliminate Non-response & Target Appropriate Lead Location (INCREMENTAL).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00399594
• Other study ID #: CAH 70-3402
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 13, 2006
• Last updated: November 20, 2015
• Start date: March 2011
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: November 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Pacing, Artificial
• Defibrillators
• Heart Failure
• Heart Failure, Congestive

Intervention

Procedure:
• A
LV lead placement in region of latest mechanical velocity (tissue doppler)
• B
LV lead placement in standard (lateral / posterolateral) position.

Locations

Country	Name	City	State
Canada	Foothills Hospital	Calgary	Alberta
Canada	London Health Sciences	London	Ontario
Canada	Quebec Heart Institute	Ste-Foy	Quebec

Sponsors (5)

Lead Sponsor	Collaborator
University of Calgary	Cambridge Heart Inc., Canadian Institutes of Health Research (CIHR), Hoffmann-La Roche, Medtronic

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in end systolic volume plus reduction in symptoms		over 12 months	No
Secondary	Minnesota Living with Heart Failure score.		Change over 12 months	No
Secondary	Short form thirty six score.		Change over 12 months	No
Secondary	Specific Activity Scale score.		Change over 12 months	No
Secondary	New York Heart Association class.		Change over 12 months	No
Secondary	Six minute walk distance.		Change over 12 months	No
Secondary	LV volumes.		Change over 12 months	No
Secondary	N-terminal pro-B-type natriuretic peptide.		Change over 12 months	No
Secondary	Mortality		Study duration	Yes
Secondary	Hospitalization		Study duration	Yes