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

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03280862
• Other study ID #: 1-10-72-330-16
• Status: Recruiting
• Phase: N/A
• Start date: March 20, 2018
• Est. completion date: June 30, 2026

Study information

• Verified date: January 2024
• Source: Aarhus University Hospital
• Contact: Jens C Nielsen
• Phone: +45 40188448
• Email: jenniels[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Branch Block, Bundle
• Bundle-Branch Block
• Heart Failure

Intervention

Device:
• Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator
Implantation of CRT-P/-D device

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Gentofte University Hospital	Gentofte
Denmark	Odense University Hospital	Odense

Sponsors (5)

Lead Sponsor	Collaborator
Aarhus University Hospital	Aalborg University Hospital, Gentofte University Hospital, Odense University Hospital, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Death	Time to death	All patients will be followed until the last included patient has been followed for two years
Secondary	Non-planned hospitalisation for heart failure	Time to first non-planned hospitalisation for heart failure	All patients will be followed until the last included patient has been followed for two years
Secondary	Sudden death	Time to sudden death	All patients will be followed until the last included patient has been followed for two years
Secondary	Cardiac death	Time to cardiac death	All patients will be followed until the last included patient has been followed for two years
Secondary	Clinical response	Increase in New York Heart Association (NYHA) class (=1 class from baseline) or improved walking distance by six-minute walk test (6MWT) (=10% from baseline)	Follow-up at 3, 6, 12, 24 and 48 months
Secondary	Quality of Life (QoL)	Changes in score from baseline to follow-up	Follow-up at 6, 12, 24 and 48 months
Secondary	Patient Reported Outcomes (PROs)	Changes in score from baseline to follow-up	Follow-up at 6, 12, 24 and 48 months
Secondary	Echocardiographic measures of LV function	Changes from baseline to follow-up in left ventricular ejection fraction (%)	Follow-up at 6, 12, 24 and 48 months
Secondary	Time to first appropriate ICD Therapy	Time to first appropriate ICD therapy (antitachycardia pacing (ATP) or shock therapy)	All patients will be followed until the last included patient has been followed for two years
Secondary	Time to first inappropriate ICD Therapy	Time to first inappropriate ICD therapy (antitachycardia pacing (ATP) or shock therapy)	All patients will be followed until the last included patient has been followed for two years
Secondary	Numbers of appropriate ICD Therapies	Numbers of appropriate ICD therapies (antitachycardia pacing (ATP) or shock therapy)	All patients will be followed until the last included patient has been followed for two years
Secondary	Numbers of inappropriate ICD Therapies	Numbers of inappropriate ICD therapies (antitachycardia pacing (ATP) or shock therapy)	All patients will be followed until the last included patient has been followed for two years
Secondary	Ventricular tachycardia (VT)/ventricular fibrillation (VF)	Time to first episode of VT/VF	All patients will be followed until the last included patient has been followed for two years
Secondary	Persistent atrial fibrillation	Recorded by the implanted device	All patients will be followed until the last included patient has been followed for two years
Secondary	Any atrial fibrillation	>30 seconds recorded by the implanted device	All patients will be followed until the last included patient has been followed for two years
Secondary	Implantation time	Procedure time at implantation	0-6 hours, assessed at completion of implantation procedure
Secondary	Fluoroscopy time	Fluoroscopy time at implantation in minutes	0-120 minutes, assessed at completion of implantation procedure
Secondary	Fluoroscopy dose	Fluoroscopy dose at implantation in mGy	Assessed <24 hours after implantation initiation
Secondary	Equipment used at implantation	Number of LV leads (0-5) used at implantation	Assessed <24 hours after implantation initiation
Secondary	Device-related outcomes	Periprocedural: lead re-operation, pneumothorax, hemothorax, pericardial bleeding/tamponade and later (30 days post implantation): LV lead re-operation, device replacement due to battery depletion, and infection requiring extraction	All patients will be followed until the last included patient has been followed for two years
Secondary	Battery replacements	Number of device replacements during the study period due to battery depletion	All patients will be followed until the last included patient has been followed for two years
Secondary	Battery longevity estimate	Measured by actual device battery longevity + estimated remaining device battery longevity as reported by the device at last study follow-up	All patients will be followed until the last included patient has been followed for two years
Secondary	QRS complex width	Changes in the ECG parameter QRS complex width during follow-up	All patients will be followed until the last included patient has been followed for two years
Secondary	QRS complex morphology	Changes in the ECG parameter QRS complex morphology during follow-up	All patients will be followed until the last included patient has been followed for two years
Secondary	Predictive value of P-wave	Predictive value of the baseline ECG parameter P-wave on clinical outcome measures in the entire cohort and between the two treatment groups	All patients will be followed until the last included patient has been followed for two years
Secondary	Predictive value of QRS complex width	Predictive value of the baseline ECG parameter QRS complex width on clinical outcome measures in the entire cohort and between the two treatment groups	All patients will be followed until the last included patient has been followed for two years
Secondary	Predictive value of QRS complex morphology	Predictive value of the baseline ECG parameter QRS complex morphology on clinical outcome measures in the entire cohort and between the two treatment groups	All patients will be followed until the last included patient has been followed for two years
Secondary	Changes in cardiac chamber dimensions	Volumes of cardiac chambers (left ventricle, left atrium, right ventricle, right atrium) measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups	All patients will be followed until the last included patient has been followed for two years
Secondary	Changes in left ventricular ejection fraction LVEF	Changes in cardiac chamber function measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups	All patients will be followed until the last included patient has been followed for two years
Secondary	Changes in right ventricular ejection fraction RVEF	Changes in cardiac chamber function measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups	All patients will be followed until the last included patient has been followed for two years