Clinical trial NCT03280862: DANISH-CRT - Does Electric Targeted LV Lead Positioning Improve Outcome in Patients With Heart Failure and Prolonged QRS
Official title: Does Targeted LV Lead Positioning Towards Latest Local Electric Activation at CRT Implantation Reduce Incidence of the Combined Endpoint "Death or Non-planned Hospitalisation for Heart Failure (HF)" in Patients With HF and Prolonged QRS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Branch Block, Bundle
Keywords: Heart Failure
Branch Block
Cardiac Resynchronization Therapy
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: Aalborg University Hospital
name: Odense University Hospital
name: Rigshospitalet, Denmark
name: Gentofte University Hospital
First posted: 2017-09-13
Enrollment: 1000
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind randomised controlled trial. Patients are included and randomised 1:1 into two groups for implantation of either

1. a CRT-D/P device with the LV lead positioned according to the latest electrical activation in the CS (intervention group) or
2. a CRT-D/P device with the LV lead positioned preferentially in a posterolateral, non-apical position (control group)
Primary purpose: TREATMENT

Brief summary: Heart failure is a leading cause of morbidity and mortality. Cardiac resynchronization therapy (CRT) is a well-established treatment for patients with symptomatic heart failure in spite of optimised medical treatment (OMT), reduced left ventricular pump function with left ventricular ejection fraction (LVEF) ≤ 35% and prolonged activation of the ventricles (bundle branch block: BBB). CRT is established by implanting an advanced pacemaker system with three leads in the right atrium, right ventricle, and in the coronary sinus (CS) for pacing the left ventricle (LV), and often is combined with an implantable defibrillator (ICD) function. On average, CRT treatment improves longevity, quality of life and functional class, and reduces heart failure symptoms. Thus, at present, CRT is indicated for heart failure patients on OMT with BBB or chronic right ventricular (RV) pacing.

It is, however, a significant problem that 30-40% of CRT patients do not benefit measurably - showing symptomatic improvement or improved cardiac pump function - from this therapy (socalled non-responders). LV lead placement is one of the major determinants of beneficial effect from CRT.

Observational studies and three randomised trials with small sample sizes indicate that targeted placement of the LV lead towards a late activated segment of the LV may be associated with improved outcome. Based on this literature, some physicians already search for late activation when positioning the LV lead. However, such a strategy was never tested in a controlled trial with a sample size sufficient to investigate important clinical outcomes. Detailed mapping for a late activation may increase operating times and infection risk, result in use of more electrodes and wires, thereby increasing costs, and increase radiation exposure for patient and staff. Placement of the LV lead in late activated areas close to myocardial scar may even result in higher risk of arrhythmia and death.

At present, it is completely unsettled whether targeted positioning of the LV lead to the latest electrically activated area of LV is superior to contemporary standard CRT with regard to improving prognosis for patients with heart failure and BBB.

The present study aims to test whether targeting the placement of the LV lead towards the latest electrically activated segment in the coronary sinus branches improves outcome as compared with standard LV lead implant in a patient population with heart failure and CRT indication.


Eligibility criteria: Inclusion Criteria:

* Heart Failure, NYHA II, III, outpatient IV
* LVEF ≤35% measured by echocardiography
* Optimal medical treatment for heart failure
* Bundle Branch Block
* Indication for primary CRT-D or CRT-P implantation or upgrade from RV pacing (pacemaker or ICD) to CRT-D or CRT-P
* Ischemic heart disease (IHD) or non-IHD
* Sinus rhythm or atrial fibrillation
* Life expectancy \>2 years
* Signed informed consent

Exclusion Criteria:

* NYHA class I
* Acute mycardial infarction (AMI) within the latest 3 months
* Coronary artery bypass graft (CABG) within the latest 3 months
* Life expectancy \<2 years
* Participation in another clinical trial of experimental treatment
* Contraindication for establishing implantable device treatment
* Previously implanted CRT system
* Does not wish to participate

Primary outcomes:
measure: Death or first non-planned hospitalisation for heart failure
timeFrame: All patients will be followed until the last included patient has been followed for two years
Secondary outcomes:
measure: Death
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Non-planned hospitalisation for heart failure
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Sudden death
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Cardiac death
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Clinical response
timeFrame: Follow-up at 3, 6, 12, 24 and 48 months
measure: Quality of Life (QoL)
timeFrame: Follow-up at 6, 12, 24 and 48 months
measure: Patient Reported Outcomes (PROs)
timeFrame: Follow-up at 6, 12, 24 and 48 months
measure: Echocardiographic measures of LV function
timeFrame: Follow-up at 6, 12, 24 and 48 months
measure: Time to first appropriate ICD Therapy
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Time to first inappropriate ICD Therapy
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Numbers of appropriate ICD Therapies
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Numbers of inappropriate ICD Therapies
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Ventricular tachycardia (VT)/ventricular fibrillation (VF)
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Persistent atrial fibrillation
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Any atrial fibrillation
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Implantation time
timeFrame: 0-6 hours, assessed at completion of implantation procedure
measure: Fluoroscopy time
timeFrame: 0-120 minutes, assessed at completion of implantation procedure
measure: Fluoroscopy dose
timeFrame: Assessed <24 hours after implantation initiation
measure: Equipment used at implantation
timeFrame: Assessed <24 hours after implantation initiation
measure: Device-related outcomes
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Battery replacements
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Battery longevity estimate
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: QRS complex width
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: QRS complex morphology
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Predictive value of P-wave
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Predictive value of QRS complex width
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Predictive value of QRS complex morphology
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Changes in cardiac chamber dimensions
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Changes in left ventricular ejection fraction LVEF
timeFrame: All patients will be followed until the last included patient has been followed for two years
measure: Changes in right ventricular ejection fraction RVEF
timeFrame: All patients will be followed until the last included patient has been followed for two years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Gentofte
country: Denmark
facility: Gentofte University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Jens C Nielsen
role: PRINCIPAL_INVESTIGATOR
References: