ALternate Site Cardiac ReSYNChronization (ALSYNC) Study (ALSYNC)

ALternate Site Cardiac ReSYNChronization Study

The ALternate site cardiac reSYNChronization (ALSYNC) study, a non-comparative, prospective, non-randomized, multi-national clinical investigation.

The purpose of this clinical investigation is to evaluate the safety and performance of the investigational atrial transseptal endocardial LV lead delivery system and the implant procedure for delivering the SelectSecure® Model 3830 lead into the Left Ventricle via a superior approach, and to evaluate the performance of the SelectSecure® Model 3830 lead in the Left Ventricle.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Device: Endocardial Left Ventricular pacing

Detailed Description

Cardiac resynchronization therapy (CRT) reduces mortality and the risk of heart failure decompensation and improves quality of life in indicated patients. However, many do not benefit due to failure to deliver the left ventricular (LV) lead via coronary sinus (5-10%) or lack of symptomatic improvement (30-40%).

The purpose of the ALSYNC Study was to evaluate the feasibility and safety of LV endocardial (LVE) pacing using a Model 3830 lead implanted by a novel pectoral atrial transseptal lead delivery system.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium
    • AZ Sint-Jan - campus Sint-Jan
  • Liège, Belgium
    • Centre Hospitalier Regional de la Citadelle
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Saint Paul's Hospital
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Centre - University Campus
• France
  • Bordeaux, France
    • Hôpital Haut-Lévêque - CHU de Bordeaux
  • Grenoble, France
    • CHU Grenoble Hôpital Michalon
  • Lyon, France
    • Infirmerie Protestante de Lyon
  • Nantes, France
    • Nouvelles Cliniques Nantaises
  • Rennes, France
    • Hopital Pontchaillou - CHU de Rennes
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem AOK
• Italy
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola - Malpighi
  • Lecco, Italy
    • Presidio Ospedaliero Alessandro Manzoni
  • Roma, Italy
    • Azienda Complesso Ospedaliero San Filippo Neri Ospedale San Filippo Neri
• Netherlands
  • Maastricht, Netherlands
    • Academisch Ziekenhuis Maastricht (AZM)
• United Kingdom
  • Belfast, United Kingdom
    • Royal Victoria Hospital
  • Glasgow, United Kingdom
    • Golden Jubilee National Hospital
  • London, United Kingdom
    • University College London Hospitals NHS Foundation Trust - The Heart Hospital
  • Southhampton, United Kingdom
    • Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cardiac Resynchronization Therapy candidate/recipient with:
• Failed Cardiac Resynchronization Therapy implant or required CRT replacement without viable access to Coronary sinus or,
• Sub-optimal Coronary sinus anatomy per investigator discretion or,
• Worsened or unchanged clinical status after Cardiac Resynchronization Therapy implant
• Patients able and willing to take optimal Vitamin K antagonist therapy (International Normalized Ratio (INR) of 2-4)
• Patients willing to sign and date the Patient Informed Consent form
• Patients 18 years of age or older
• Patients able and willing to comply with the protocol, and is expected to remain available for follow-up visits

Exclusion Criteria:

• Patients having contraindications to Vitamin K antagonist therapy
• Patients contraindicated for < 100 micrograms beclomethasone dipropionate
• Patients unable to tolerate an urgent thoracotomy
• Documented (previous) ischemic or hemorrhagic stroke
• Patients with known previous atrial septal defect closure, or history of mural thrombus that has not been resolved
• Patients with documented atrial fibrillation AND increased stroke risk as determined by the Congestive Heart Failure, Hypertension, Age(2), Diabetes, Stroke(2), Vascular disease, Age, and Sex Category (CHA2DS2-VASc) Score of equal to or greater than 5
• Patients with unstable angina pectoris or who have had an acute myocardial infarct within the past 30 days
• Patients with known atrial septum defect (ASD) and/or left superior vena cava
• Patient with known internal carotid artery stenosis of greater than 50%
• Patients diagnosed with peripheral artery disease that are expected to undergo stenting within the next three months
• Patients who have had a Coronary artery bypass graft or stent within the past three months
• Patients with history of mitral or aortic valve repair or replacement
• Post heart transplant patients (patients waiting for heart transplant are allowed in the study)
• Patients currently undergoing dialysis treatment
• Patients with ongoing chemotherapy and radiation therapy that may have an effect on cardiac function
• Patients with ongoing Adverse Events from a previous Left Ventricle lead implant attempt
• Patients enrolled in any concurrent drug and/or device study that may confound the results of this study
• Patients who are not expected to survive more than twelve months
• Patients with exclusion criteria required by local law

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endocardial Left Ventricular pacing; All patients will undergo the intervention, and are followed at 1, 3, 6, and 12 months (minimum) and biannually thereafter until 1 year after enrollment of the last patient.	Device: Endocardial Left Ventricular pacing; Subjects receive an endocardial LV lead placement via superior approach using Medtronic Model 3830 lead and Medtronic Model 6227ATS deflectable delivery catheter and Medtronic Model 6248HS, 6248JL, or 6248JS delivery catheter, using trans esophageal echo (TEE) or intra-cardiac echo (ICE) to guide the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Free From Lead, Delivery System and Implant Related Complications.	Adverse events were reviewed by an independent Adverse Event Adjudication Committee. Events classified as complication related to the LV endocardial lead, the investigational delivery system or the implant procedure contribute to the outcome. The percentage of patients free from such complication at 6 months after the procedure was estimated using the Kaplan-Meier method and is reported with the corresponding 95% confidence interval.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implant Success	Number of participants with a successful implant of Model 3830 lead.	Implant
Number of Questionnaires Reporting None of the Handling and Implant Characteristics as Poor	Questionaires were collected for each LV lead implant attempt, reattempt, and LV lead modification. To evaluate the ease of positioning of the Model 3830 lead and the Models 6227ATS and 6248HS, JS, JL catheters, a rating scale of Poor, Fair, Good, Very good, and Excellent was used for each of the ten questions on the questionnaire. Outcome reports the number of questionnaires where no single question was answered with Poor.	Implant
Bipolar Sensing Amplitude of the Model 3830 Lead in the LV at 12 Months	Sensing amplitude measurement was taken with the implanted device at the 12 month follow-up visit.	12 months
Bipolar Pacing Threshold of the Model 3830 Lead in the LV at 12 Months	Bipolar measurement of Model 3830 lead voltage threshold at 0.4ms pulse width using the implanted device at the 12 month visit	12 months
Bipolar Pacing Impedance of the Model 3830 Lead in the LV at 12 Months	Measurement of Impedance of the Model 3830 Lead in the LV using the implanted device at the 12 month visit	12 months
Subjects With 1 Class of NYHA Improvement From Baseline to 6 Months	NYHA Class change was evaluated between baseline and the 6 months visit. Reported are the subjects with at least 1 class improvement from baseline to 6 months	baseline and 6 months
Distance Walked at 6 Minute Hall Walk at the 12 Month Visit	Distance walked at the 6 minute hall walk test at the 12 month visit	12 months
Percent Change in Left Ventricular Ejection Fraction From Baseline to 6 Months	Percent change in Left Ventricular Ejection Fraction (LVEF) was measured from baseline to 6 months	baseline and 6 months
Milliliters Change in Left Ventricular End-Systolic Volume at 6 Months	Milliliters change in Left Ventricular End-Systolic Volume (LVESV) from baseline to 6 months	6 months
Millimeters Change in Left Ventricular End-Diastolic Diameter From Baseline to 6 Months	Millimeters change in Left Ventricular End-Diastolic Diameter (LVEDD) from baseline to 6 months	baseline and 6 months
Number of Subjects With Mitral Regurgitation Improvement of at Least One Class From Baseline to 6 Months	Reported is the number of patients with at least one class improvement from baseline to 6 months	baseline and 6 months
Change in (NT-pro)BNP Levels From Baseline to 6 Months	Change in either Brain Natriuretic Peptide (BNP) or N-Terminal-prohormone BNP (NT-proBNP) levels from baseline to 6 months	baseline and 6 months

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Principal Investigator: Professor John Morgan, MD, Spire Southampton Hospital

Publications and helpful links

General Publications

• Biffi M, Defaye P, Jais P, Ruffa F, Leclercq C, Gras D, Yang Z, Gerritse B, Ziacchi M, Morgan JM; ALSYNC Investigators. Benefits of left ventricular endocardial pacing comparing failed implants and prior non-responders to conventional cardiac resynchronization therapy: A subanalysis from the ALSYNC study. Int J Cardiol. 2018 May 15;259:88-93. doi: 10.1016/j.ijcard.2018.01.030.
• Morgan JM, Biffi M, Geller L, Leclercq C, Ruffa F, Tung S, Defaye P, Yang Z, Gerritse B, van Ginneken M, Yee R, Jais P; ALSYNC Investigators. ALternate Site Cardiac ResYNChronization (ALSYNC): a prospective and multicentre study of left ventricular endocardial pacing for cardiac resynchronization therapy. Eur Heart J. 2016 Jul 14;37(27):2118-27. doi: 10.1093/eurheartj/ehv723. Epub 2016 Jan 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: January 11, 2011
• First Submitted That Met QC Criteria: January 14, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Actual): June 20, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ALSYNC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO