The Left Ventricular Assist Device (LVAD) Off or On Pump Implantation Study (LVAD-ON-OFF)

The Left Ventricular Assist Device Off or On Pump Implantation Study: A Single-center Randomized Trial (LVAD-ON-OFF)

The purpose of this study is to compare adverse events after off-pump LVAD surgery or on-pump LVAD surgery.

Study Overview

• Status: Terminated
• Conditions: Heart Failure; LVAD
• Intervention / Treatment: Device: Off-Pump; Device: On-Pump

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

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:

• The patient has had a diagnosis of end stage heart failure, New York Heart association (NYHA) class III or IV HF for a minimum of 90 days prior to screening.
• The patient has guideline-directed medical therapy according to American College of Cardiology(ACC)/American Heart Association (AHA)/European Society of Cardiology(ESC) heart failure(HF) guidelines
• The patient has an Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score of 1-3.
• Left ventricular assist device (LVAD) placement is intended as a bridge to transplant (BTT) or destination therapy (DT) with either HeartWare Ventricular Assist Device (HVAD) or HeartMate III LVAD.
• The patient is able to sign informed consent form and Release of Medical Information Form.
• The patients is willing and able to participate in scheduled follow-up appointments.

Exclusion Criteria:

• The patient requires concomitant surgery for left ventricular or atrial appendage closure or the patient has severe aortic insufficiency, mitral stenosis, or severe tricuspid regurgitation.
• The patient has an intracardiac thrombus or other mass diagnosed by echocardiography, left ventriculogram, or other imaging.
• Planned insertion of right ventricular(RV) support device (either temporary or permanent).
• The patient has suffered an acute cardiovascular event such as acute coronary syndrome (ST elevation myocardial infarction (STEMI) or Non-ST elevation myocardial infarction (NSTEMI), or unstable angina, or underwent any cardiac surgery or interventional cardiac or peripheral vascular procedure within 30 days prior to LVAD implantation.
• The patient has had ischemic or hemorrhagic stroke as diagnosed by CT or MRI within 90 days prior to study enrollment.
• The patient had prior heart or other organ transplantation, or surgically implanted LVAD or cardiac shunt.
• The patient will likely need an immediate heart transplant due to hemodynamic instability.
• The patient has had a known active malignancy or treatment for cancer within the past year except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer that has been definitively treated.
• The patient has history of any malignancy where expected survival is less than two years. Past medical history of cancer is not exclusionary as long as subject has been disease-free for at least one years since the time of diagnosis and treatment.
• Patient has a severe co-morbidity (current need for hemodialysis or current glomerular filtration rate(GFR) ≤20 mL/minute/1.73 m2 estimated by Modification of Diet in Renal Disease( MDRD)calculation; hepatic impairment defined as liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)] >3x Upper Limit of Normal within 30 days prior to LVAD implantation or known objectively confirmed intrinsic liver disease (e.g., cirrhosis, chronic hepatitis B or hepatitis C virus infection)).
• The patient has a known bleeding diathesis or thrombocytopenia defined as platelet count <50,000 platelets/μL.
• The patient has peri/postpartum cardiomyopathy, or is a pregnant or lactating woman, or a woman of child-bearing age not using a suitable method of contraception.
• The patient, who in the absence of an Implantable Cardioverter Defibrillator (ICD) (or any implanted device capable of defibrillation), has a history of malignant ventricular arrhythmia or sustained ventricular tachycardia (VT), with sustained VT demonstrated by Q wave R wave S wave (QRS) complexes wider than 120 milliseconds, lasting more than 30 seconds, and with a rate of more than 100 beats per minute on screening ECG or other data supporting this diagnosis.
• Recent history of psychiatric disease, including drug or alcohol abuse, that is likely to impair, in the opinion of the investigator, the subject's ability to comply with protocol-mandated procedures.
• Participation in any other clinical investigation that is likely to confound study results or affect study outcome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Off-Pump	Device: Off-Pump; After a standard median sternotomy, pericardium will be divided to expose the heart and major vessels, and the aortic cannulation sutures will be placed. Pyramid positioner will be applied to the apex of the heart, and the heart will be manually elevated upward. The inflow cannula placement location and placement of the sewing ring will be done with pledged sutures. The LV diaphragmatic site coring will be completed, and immediate LV digital exploration will be accomplished. The LVAD inflow cannula will be inserted through the sewing ring into the LV cavity. Upon completing proper LVAD inflow cannula placement into the LV and securing it in position, the heart will be dropped into the pericardial cavity with the outflow graft elevated for LVAD and outflow graft de-airing and to prevent potential later air embolization. A partial occlusion clamp will be placed on the ascending aorta and appropriately trimmed outflow graft will be sewn to the aorta.
ACTIVE_COMPARATOR: On-Pump	Device: On-Pump; A standard median sternotomy incision will be performed and pericardium divided to expose the heart and major vessels. Cannulation will be done through the aorta and the right atrium and the patient will be put on cardiopulmonary bypass (CPB). The patient's heart will be freed from the surrounding tissues. With a cylindrical blade, the surgeon will excise a core of myocardium from the apex. The LVAD sewing ring will then be sutured to the margins of the apical hole. The LVAD will be inserted into the LV cavity through the sewing ring. The outflow graft will be measured for the anastomosis into the aortic root. Partial occlusion clamp will be placed on the aortic root and the anastomosis will be performed. De-airing will be performed and the LVAD will be started. The patient will then be weaned from CPB and decannulated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With the Composite Outcome of Moderate or Severe Right Ventricular (RV) Dysfunction (Perioperative Right Heart Failure), Severe Renal Dysfunction Requiring Renal Replacement Therapy, Thrombotic Complications, or Death From Any Cause	Perioperative right ventricular (RV) failure is defined by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scoring as the need for intravenous inotropes for >14 days post-operatively or a right ventricular assist device (RVAD). RV function will be measured by tricuspid annular plane systolic excursion (TAPSE) values assessed using echocardiography. Additionally, hemodynamic evidence of RV dysfunction will also be collected with: a right-atrial pressure (RAP): pulmonary capillary wedge pressure (PCWP) ratio of ≥ 0.67. A thrombotic complication is defined as any thromboembolic event (transient ischemic attack or stroke objectively confirmed with computed tomography) or confirmed pump thrombus.	from time of implantation to 30 days post-implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Need for Blood Product Transfusion Within 48-hours Post-implantation		from time of implantation to 48 hours post-implantation
Operative Safety as Indicated by the Number of Participants Who Died Within 30 Days Post-implantation		from time of implantation to 30 days post-implantation
Operative Safety as Indicated by Chest Tube Output Within 24 Hours of Implantation		from time of implantation to 24 hours post-implantation
Operative Safety as Indicated by Number of Participants Who Underwent Post-operative Re-exploration for Bleeding		from time of implantation to 30 days post-implantation
Number of Participants With Allosensitization	Allosensitization is defined as calculated panel reactive antibody (cPRA) greater than 10%.	30 days post-implantation
Number of Participants With Allosensitization	Allosensitization is defined as calculated panel reactive antibody (cPRA) greater than 10%.	6 months post-implantation
Number of Participants With Allosensitization	Allosensitization is defined as calculated panel reactive antibody (cPRA) greater than 10%.	12 months post-implantation
Number of Readmissions for Heart Failure		from time of implantation to 1 year post-implantation
Overall Hemostatic Potential		Baseline
Overall Coagulation Potential		Baseline
Overall Fibrinolytic Potential		Baseline
Overall Hemostatic Potential		48 hours post-implantation
Overall Coagulation Potential		48 hours post-implantation
Overall Fibrinolytic Potential		48 hours post-implantation
Number of Participants With Major Bleeding	Major bleeding is defined as an episode of suspected internal or external bleeding that results in one or more of the following: death, re-operation, hospitalization, transfusion of red blood cells according to INTERMACS definition.	30 days post-implantation
Number of Participants With Major Bleeding	Major bleeding is defined as an episode of suspected internal or external bleeding that results in one or more of the following: death, re-operation, hospitalization, transfusion of red blood cells according to INTERMACS definition.	6 months post-implantation
Number of Participants With Major Bleeding	Major bleeding is defined as an episode of suspected internal or external bleeding that results in one or more of the following: death, re-operation, hospitalization, transfusion of red blood cells according to INTERMACS definition.	12 months post-implantation

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Igor D Gregoric, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2020
• Primary Completion (ACTUAL): May 25, 2021
• Study Completion (ACTUAL): March 31, 2022

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (ACTUAL): January 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 27, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: LVAD
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: HSC-MS-19-0926

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No