Lavare Cycle in Patients Receiving HeartWare Left Ventricular Assist Device

Study Overview
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Brief Summary
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Left ventricular assist device (LVAD) patients remain at risk for pump thrombus and thromboembolic events through multiple mechanisms. The HeartWare® Ventricular Assist System (HVAD®, HeartWare Inc., Framingham, MA, USA) includes a novel speed modulation feature called Lavare™ cycle. The Lavare™ Cycle is aimed to promote washing of left ventricle to decrease blood stasis and subsequent risk of thrombus formation, ingestion and/or expulsion. No prior study has prospectively evaluated the impact of Lavare™ cycle on patient outcomes in a randomized fashion. We intend to assess effects of Lavare™ Cycle among patients receiving HVAD LVAD in this randomized controlled pilot project.

Detailed Description
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Left ventricular assist device (LVAD) patients remain at risk for pump thrombus and thromboembolic events through multiple mechanisms. The HeartWare® Ventricular Assist System (HVAD®, HeartWare Inc., Framingham, MA, USA) includes a novel speed modulation feature called Lavare™ cycle. It consists of 3 phases: phase 1 - a 200 rpm decrease from baseline speed for 2 seconds, phase 2 - a 100 rpm increase from baseline for 1 second and phase 3 - return of speed to baseline; this cycle repeats itself once every minute. The LavareTM Cycle is aimed to promote washing of left ventricle to decrease blood stasis and subsequent risk of thrombus formation, ingestion and/or expulsion. In a post-hoc analysis of ReVOLVE registry, which includes 248 patients implanted with the HVAD following Conformité Européenne Mark in nine centers in Europe and Australia, no adverse impact on survival was observed with Lavare™ cycle. Additionally, lower risk of stroke, sepsis and right heart failure was observed among those with Lavare™ cycle in the above-mentioned study. However, no prior study has prospectively evaluated the impact of Lavare™ cycle on patient outcomes in a randomized fashion. In this prospective randomized controlled trial, we intend to assess the role of Lavare™ cycle in pump related complications.

Official Title
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Assessment of Lavare Cycle Implementation Among Patients Following HeartWare Left Ventricular Assist Device Implantation: A Prospective Randomized Controlled Pilot Study

Conditions
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Thromboembolism, Hemolysis, Stroke

Intervention / Treatment
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* Device: Lavare On
* Device: Lavare Off


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Approved for or supported with HeartWare durable LVAD Capable of giving informed consent Exclusion Criteria: For those undergoing new device implantation: Age <18 years Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 at the time of implantation Presence of intra-cardiac thrombus History of thromboembolic event within previous 3 months of enrollment For those with prior LVAD implantation with on-going support: Support duration <3 months History of prior LVAD pump exchange History of LVAD pump hemolysis or thrombosis as defined by INTERMACS criteria History of stroke or transient ischemic event within previous 3 months of enrollment History of post-LVAD severe right ventricular failure as defined by INTERMACS criteria within previous 3 months of enrollment History of pump-related infection treated within previous 3 months of enrollment or those on chronic antibiotics suppressive therapy for pump related infection History of post-LVAD intra-cardiac or arterial thrombus or thromboembolic event within previous 3 months of enrollment International Normalized Ratio (INR) <2 within previous 30-days from the date of enrollment Aspirin dose <325 mg/day Lactate Dehydrogenase (LDH) levels ≥ 3 times the upper normal limit in previous 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lavare Cycle On<br>For the patients randomized to Lavare On group, the Lavare™ cycle will be turned on upon device interrogation after patients return to intensive care unit from the operating room. | Device: Lavare On<br>* For the patients randomized to Lavare On group, the Lavare™ cycle will be turned on upon device interrogation after patients return to intensive care unit from the operating room.<br>|
| Active Comparator: Lavare Cycle Off<br>For the patients randomized to Lavare Off group, the Lavare™ cycle will be turned off upon device interrogation after patients return to intensive care unit from the operating room. | Device: Lavare Off<br>* For the patients randomized to Lavare Off group, the Lavare™ cycle will be turned off upon device interrogation after patients return to intensive care unit from the operating room.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint of Total Ischemic Events, Thromboembolic Events, Pump Hemolysis or Thrombosis, Pump Exchange | INTERMACS definitions of cerebrovascular events, pump hemolysis/ thrombosis will be used. Pump malfunction needing device exchange or emergent transplant will also be included in the main composite event | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | death from any cause | 6 months | 
| Survival to Transplantation | Number of days supported on LVAD until transplant | 6 months | 
| Rehospitalizations | Any cardiac and non-cardiac re-hospitalizations since trial enrollment | 6 months | 
| Mucosal Bleeding | Epistaxis, gastrointestinal bleeding, urological bleeding events will be analyzed | 6 months | 
| Right Ventricular Failure | INTERMACS definitions for Right ventricular failure will be analyzed | 6 months | 
| Device Related Infection | LVAD device systems related infections will be analyzed | 6 months | 
| Aortic Insufficiency | Echocardiographic evidence will be used to define severity of aortic insufficiency | 6 months | 
| Change in 6 Minute Walk Test | The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. | Baseline to 6 months | 
| Changes in New York Heart Association Class | Functional class will be assessed at baseline and during follow up to assess improvement in functional status | Baseline to 6 months | 
| Quality of Life Measured by The Kansas City Cardiomyopathy Questionnaire | Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The score can range from 0-100, in which higher scores reflect better health status. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lavare Cycle, HeartWare LVAD, Thromboembolic events