Hemolysis, Stroke, Thromboembolism
Conditions
Keywords
Lavare Cycle, HeartWare LVAD, Thromboembolic events
Brief summary
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
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.
Interventions
DEVICELavare On
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.
DEVICELavare Off
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.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Approved for or supported with HeartWare durable LVAD 3. Capable of giving informed consent
Exclusion criteria
1. For those undergoing new device implantation: 1. Age \<18 years 2. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 at the time of implantation 3. Presence of intra-cardiac thrombus 4. History of thromboembolic event within previous 3 months of enrollment 2. For those with prior LVAD implantation with on-going support: 1. Support duration \<3 months 2. History of prior LVAD pump exchange 3. History of LVAD pump hemolysis or thrombosis as defined by INTERMACS criteria 4. History of stroke or transient ischemic event within previous 3 months of enrollment 5. History of post-LVAD severe right ventricular failure as defined by INTERMACS criteria within previous 3 months of enrollment 6. History of pump-related infection treated within previous 3 months of enrollment or those on chronic antibiotics suppressive therapy for pump related infection 7. History of post-LVAD intra-cardiac or arterial thrombus or thromboembolic event within previous 3 months of enrollment 8. International Normalized Ratio (INR) \<2 within previous 30-days from the date of enrollment 9. Aspirin dose \<325 mg/day 10. Lactate Dehydrogenase (LDH) levels ≥ 3 times the upper normal limit in previous 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint of Total Ischemic Events, Thromboembolic Events, Pump Hemolysis or Thrombosis, Pump Exchange | 6 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival to Transplantation | 6 months | Number of days supported on LVAD until transplant |
| Rehospitalizations | 6 months | Any cardiac and non-cardiac re-hospitalizations since trial enrollment |
| Mucosal Bleeding | 6 months | Epistaxis, gastrointestinal bleeding, urological bleeding events will be analyzed |
| Right Ventricular Failure | 6 months | INTERMACS definitions for Right ventricular failure will be analyzed |
| All-cause Mortality | 6 months | death from any cause |
| Aortic Insufficiency | 6 months | Echocardiographic evidence will be used to define severity of aortic insufficiency |
| Change in 6 Minute Walk Test | Baseline to 6 months | 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. |
| Changes in New York Heart Association Class | Baseline to 6 months | Functional class will be assessed at baseline and during follow up to assess improvement in functional status |
| Quality of Life Measured by The Kansas City Cardiomyopathy Questionnaire | 6 months | 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. |
| Device Related Infection | 6 months | LVAD device systems related infections will be analyzed |
Countries
United States
Participant flow
Pre-assignment details
9 participants signed informed consent. One patient was not randomized due to improved health. Total of 8 patients were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Lavare Cycle On 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.
Lavare On: 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. | 4 |
| Lavare Cycle Off 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.
Lavare Off: 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. | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Sponsor Withdrew the device off market; study stopped | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Lavare Cycle On | Total | Lavare Cycle Off |
|---|---|---|---|
| Age, Continuous | 55 years | 54.5 years | 54.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 2 Participants |
| Region of Enrollment United States | 4 participants | 8 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 2 / 4 | 4 / 4 |
Outcome results
Primary
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
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
All-cause Mortality
death from any cause
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Aortic Insufficiency
Echocardiographic evidence will be used to define severity of aortic insufficiency
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
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.
Time frame: Baseline to 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Changes in New York Heart Association Class
Functional class will be assessed at baseline and during follow up to assess improvement in functional status
Time frame: Baseline to 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Device Related Infection
LVAD device systems related infections will be analyzed
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Mucosal Bleeding
Epistaxis, gastrointestinal bleeding, urological bleeding events will be analyzed
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
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.
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Rehospitalizations
Any cardiac and non-cardiac re-hospitalizations since trial enrollment
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Right Ventricular Failure
INTERMACS definitions for Right ventricular failure will be analyzed
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.
Secondary
Survival to Transplantation
Number of days supported on LVAD until transplant
Time frame: 6 months
Population: Data analysis was not completed because only one participant completed each arm and showing data could violate privacy interests. The department also did not allocate resources for further analysis as the trial was terminated early and was missing sufficient samples and data points for the prespecified analysis.