Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy. (OPTIMISE-CRT)

This study has been completed.
Sponsor:
Collaborator:
St. Jude Medical
Information provided by (Responsible Party):
Dr. Derek Exner, University of Calgary
ClinicalTrials.gov Identifier:
NCT00489177
First received: June 20, 2007
Last updated: November 12, 2012
Last verified: November 2012
  Purpose

This international study is assessing if repeat adjustment of the timing between the three leads in a cardiac resynchronization therapy (CRT) defibrillator will increase the likelihood of benefit (symptoms and heart function) compared to usual device programming. The hypothesis is that QuickOpt facilitated serial optimization of sensed atrioventricular (sAV), paced atrioventricular (pAV), and inter-ventricular (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.


Condition Intervention Phase
Heart Failure
Device: A
Device: B
Phase 4

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 461
Study Start Date: June 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
QuickOpt
Device: A
QuickOpt intra-cardiac electrogram optimization
Placebo Comparator: B
Usual care
Device: B
Single optimization in initial month post-implant

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CRT-D indications and be implanted with an SJM CRT-D device with VV timing and a compatible lead system.
  2. Able to complete a 6-minute hall walk with the only limiting factor to be fatigue or shortness of breath.
  3. Geographically stable and willing to comply with follow-up.
  4. Adequate echocardiographic images to measure LV end systolic volume.

Exclusion Criteria:

  1. Epicardial ventricular lead system.
  2. Ability to walk ≥ 450 meters in 6 minutes
  3. Limited intrinsic atrial activity (≤ 40 bpm).
  4. Persistent or permanent AF.
  5. 2° or 3° heart block.
  6. Life expectancy is less than 1 year.
  7. Patient is pregnant.
  8. Receiving IV inotropic agents.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489177

Locations
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4N1
Sponsors and Collaborators
University of Calgary
St. Jude Medical
Investigators
Principal Investigator: Derek V Exner, MD, MPH University of Calgary
  More Information

No publications provided

Responsible Party: Dr. Derek Exner, Professor, University of Calgary
ClinicalTrials.gov Identifier: NCT00489177     History of Changes
Other Study ID Numbers: 73-1726
Study First Received: June 20, 2007
Last Updated: November 12, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by University of Calgary:
cardiac resynchronization therapy
response
Defibrillators

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2014