Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy. (OPTIMISE-CRT)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy.|
- Clinical benefit (reduction in SAS of at least 1 class or a 25% or larger improvement in 6 minute hall walk distance) plus structural remodeling (15% or greater reduction in left LV end systolic volume or ≥ 5% absolute improvement in echo-derived LV EF) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Rate of late (12-month) versus early (3 month) response to CRT [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
- Changes in BNP [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
- Inter-/intra-ventricular dysynchrony [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Active Comparator: A
QuickOpt intra-cardiac electrogram optimization
Placebo Comparator: B
Single optimization in initial month post-implant
Cardiac resynchronization therapy (CRT) is primarily designed to synchronize the mechanical activity of the heart. While CRT is beneficial in average, a sizable proportion of patients do not clearly benefit from (respond to) CRT. Whether routinely optimizing the timing between the atria and ventricles (AV timing) and the timing between the left and right ventricles (VV timing) will significantly increase the likelihood of patients benefiting from (responding to) CRT is unknown.
The combination of simple and reliable measures of functional capacity (specific activity score [SAS] and 6-minute walk distance) with echocardiographic measures of left ventricular (LV) volume and ejection fraction (EF) is a practical way of defining response to CRT.
Based on surveys, most patients receiving CRT devices do not have formal optimization of AV and VV timing. This is largely because the usefulness of this is questionable and significant resources are required to perform detailed echo measurements.
A method for estimating optimal sensed AV (sAV), paced AV (pAV), and VV timing using intra-cardiac electrograms (I-EGM) has been developed (QuickOptTM) and offers a quick, simple and inexpensive means to optimize both CRT timing. However, the utility of QuickOptTM optimization is unproven.
Primary hypothesis. QuickOpt facilitated serial optimization of sAV, pAV, and VV timing in the initial 9 months following successful CRT will increase the rate of clinical response and structural remodeling at 12 months compared to usual care. Clinical response will be defined as a reduction in SAS of > 1 class or a 25% or larger improvement in 6 minute hall walk distance at 12 months versus baseline. Structural remodeling will be defined as a 15% or greater reduction in left LV end systolic volume or ≥ 5% absolute improvement in echo-derived LV EF at 12 months versus baseline.
Methods. Initially a sub-study of FREEDOM (NCT00418314). Now an independent trial. Double-blind randomized comparison of serial QuickOpt optimization of sAV, pAV, and VV timing (QuickOpt) versus usual care (Usual) in patients with highly symptomatic heart failure undergoing CRT implantation. Stratification by etiology of LV dysfunction will be undertaken. Serial optimization of sAV, pAV, and VV timing will be performed in the QuickOptTM group immediately post-randomization, and at 3, 6, and 9 months post-randomization. Final outcome will be assessed at 12 months post-randomization.
Statistical aspects. 450 patients (225 / group) will provide 85% power to detect a 15% absolute improvement in the rate of response to CRT with QuickOptTM versus usual care. The proportion of responders will be compared using a Mantel-Haenszel stratified analysis adjusted for lead position (anterior versus non-anterior) and using an intention-to-treat analysis.
Overview. Up to 50 sites in Canada, Europe, Asia and the United States will enroll patients over 36 months. Countries presently enrolling patients include: Canada, the United States, Switzerland, Italy, Belgium, Denmark, Austria, France, Spain, the United Kingdom, the Netherlands, China, Hong Kong and Japan.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00489177
|University of Calgary|
|Calgary, Alberta, Canada, T2N 4N1|
|Principal Investigator:||Derek V Exner, MD, MPH||University of Calgary|