DANISH-CRT - Does Electric Targeted LV Lead Positioning Improve Outcome in Patients With Heart Failure and Prolonged QRS

NCT03280862 | Active Not Recruiting

• 1 other identifier: 1-10-72-330-16
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 5

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.

Conditions

Heart Failure; Branch Block, Bundle

Keywords

Heart Failure; Branch Block; Cardiac Resynchronization Therapy

Outcome Measures

Primary Outcomes (1)

• Death or first non-planned hospitalisation for heart failure

  Time to death or first non-planned hospitalisation for heart failure

  All patients will be followed until the last included patient has been followed for two years

Secondary Outcomes (30)

• Death

  All patients will be followed until the last included patient has been followed for two years

• Non-planned hospitalisation for heart failure

  All patients will be followed until the last included patient has been followed for two years

• Sudden death

  All patients will be followed until the last included patient has been followed for two years

• Cardiac death

  All patients will be followed until the last included patient has been followed for two years

• Clinical response

  Follow-up at 3, 6, 12, 24 and 48 months

Study Arms (2)

Control

ACTIVE COMPARATOR

Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator with the LV lead positioned preferentially in a posterolateral, non-apical position

Device: Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator

Intervention

EXPERIMENTAL

Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator with the LV lead positioned according to the latest electrical activation in the CS

Device: Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator

Interventions

Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator DEVICE

Implantation of CRT-P/-D device

Control; Intervention

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Aalborg University Hospital: collaborator
• Odense University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Gentofte University Hospital: collaborator

Study Sites (5)

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Gentofte University Hospital

Gentofte Municipality, 2900, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (1)

• Kronborg MB, Frausing MHJP, Svendsen JH, Johansen JB, Riahi S, Haarbo J, Poulsen SH, Eiskjaer H, Kober L, Ovrehus K, Sommer AM, Schou M, Norgaard BL, Risum N, Poulsen MK, Sogaard P, Sandgaard N, Kofoed KF, Hansen TF, Graff C, Pedersen SS, Skals RG, Nielsen JC. Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure? Am Heart J. 2023 Sep;263:112-122. doi: 10.1016/j.ahj.2023.05.011. Epub 2023 May 21.

  PMID: 37220821 DERIVED

MeSH Terms

Conditions

Heart Failure; Bundle-Branch Block

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Heart Block; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jens C Nielsen

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients are unaware of treatment arm. All patients undergo the same pre-implant program and follow-up. Healthcare personel performing follow-up are blinded for treatment arm. Outcome events are evaluated by a committee blinded for treatment arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, DMSc, PhD, FESC, FEHRA

Model Details: 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)

Study Record Dates

• First Submitted: June 8, 2017
• First Posted: September 13, 2017
• Study Start: March 20, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (5)