Heart Failure
Conditions
Keywords
Medical Device, Thoracic Surgical Procedure, Pumps Heart Assist, Ventricular Assist Device
Brief summary
The purpose of the study is to evaluate the safety and effectiveness of the HW005 System in patients listed for cardiac transplantation with refractory, advanced heart failure at risk of death.
Detailed description
The primary endpoint is success at 180 days which is expressed as a simple proportion and defined as alive on the originally implanted HW005 or transplanted or explanted for recovery. Patients must survive 60 days post-explant for recovery to be considered successful. The primary endpoint is not statistically powered. The six eligible implanted cases will be evaluated as a proportion of success accompanied by a 95% exact confidence interval and presented alongside the ADVANCE results for visual comparison.
Interventions
DEVICEImplant of the HW005 Ventricular Assist System.
The HW005 Pump is in implantable centrifugal pump that was designed to provide flows up to 10 L/min. It is a small device which is both lightweight and simple to use.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with irreversible end-stage heart failure of New York Heart Association (NYHA) class III or IV and a history of class IV who are eligible for heart transplantation. 2. Patients who are dependent on medication of inotropes or intra-aortic balloon pump (IABP). 3. Body Surface Area (BSA) ≥1.2 m2. In addition other factors may be taken into consideration, including chest size, abdominal fat (lack of abdominal fat may preclude a pump pocket) and any other physical characteristics that might be benefited by an intra-pericardial pump in a small person. 4. Patients who are aged less than 65 years of age. 5. Patients must be able to understand the limits and complications associated with the HW005 Ventricular Assist System. 6. Female patients of childbearing potential must agree on contraception for the duration of the study. 7. The patient or the legal representative has signed the informed consent form.
Exclusion criteria
1. Severe illness other than heart disease which would exclude cardiac transplantation. 2. Inadequate family/social support. 3. Active, uncontrolled infection despite appropriate antibiotic, antiviral or antifungal treatment. 4. Existence of any ongoing mechanical circulatory support (MCS) other than an IABP. 5. Prior cardiac transplant or cardiomyoplasty. 6. Acute myocardial infarction within 14 days of implant. 7. Uncorrected thrombocytopenia or generalized coagulopathy. 8. Intolerance to anticoagulant or antiplatelet therapies or any other peri- or postoperative therapy that the investigator may administer based upon the patient's health status. 9. Patients for whom the use of a left ventricular assist device (LVAD) is contraindicated due to an ongoing aortic/cardiac aneurysm, intraventricular septum rupture and/or use of a mechanical heart valve. 10. Etiology of heart failure is due to, or associated with, uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis, active myocarditis or restrictive cardiomyopathy. 11. Patients with irreversible hepatic dysfunction. 12. Patients with irreversible renal dysfunction. 13. Pregnancy. 14. Patients with serious chronic obstructive pulmonary disease (COPD) (Forced Expiratory Volume in the first second (FEV1) \< 50%). 15. Pulmonary vascular resistance is unresponsive (fixed) to pharmacologic manipulation as demonstrated by a pulmonary artery systolic pressure exceeding 60mmHg in conjunction with any one of the two following variables: * Pulmonary vascular resistance is greater than 6 Woods Units or * Transpulmonary gradient exceeds 15 mmHg 16. Cardiothoracic surgery within 14 days of implantation. 17. Peripheral vascular disease with rest pain or ischemic ulcers of the extremities. 18. Pulmonary embolus within three weeks of enrollment as documented by computed tomography (CT) scan or nuclear scan. 19. Patients have moderate to severe aortic insufficiency without plans for correction during pump implantation surgery. Correction may include aortic valve repair at the time of implant. 20. The patient who has advanced calcification in the ascending aorta and/or the descending aorta. 21. Serious right heart failure as defined by the anticipated need for right ventricular assist device (RVAD) support or extracorporeal membrane oxygenation (ECMO) at the time of screening. 22. Patients with severe central nervous system disorder or severe cerebral vascular disorder. 23. Patients with a history of drug intoxication, alcohol dependence. 24. Patients unwilling or unable to comply with study requirements. 25. Patients who refuse transfusion. 26. Patients who in the investigator judgement are deemed to be unsuitable as a subject. 27. Patients who are participating in another clinical trial involving investigational drugs or devices.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Alive on the Implanted HW005 Ventricular Assist System or Transplanted or Explanted for Recovery at 180 Days | 180 days | The primary endpoint is success at 180 days which is defined as alive on the originally implanted HW005 Ventricular Assist System or transplanted or explanted for recovery. Patients must survive 60 days post-explant for recovery to be considered successful. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of All Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) | Through study completion, an average of 44.5 months | SAEs are defined as events that result in death, are life-threatening, result in permanent disability, require medical treatment to prevent permanent disability or require surgical intervention or hospitalization. UADEs are defined as any serious adverse device effect which by its nature, incidence, severity or outcome has not been identified in the current version of the risk analysis report. Events were categorized using the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) definitions. |
| Incidence of All Device Failures and Device Malfunctions. | Through study completion, an average of 44.5 months | The device failures and malfunctions are the failures on pumping function due to thrombosis inside/outside of the implanted pump, the mechanical failures of the implanted components, the mechanical failures of the external components and the failures due to the user. Events were categorized using the J-MACS definitions. |
| Number of Participants Alive on the Implanted HW005 Ventricular Assist System at 180 Days | 180 days | — |
| Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Screening, Month 6 (180 days) and Month 24 (after FU completion) | The New York Heart Association (NYHA) Functional Classification places patients with heart failure in one of four categories based on how much they are limited during physical activity. Class I (best): No limitation of physical activity. Class II: Slight limitation of physical activity. Comfortable at rest. Class III: Marked limitation of physical activity. Comfortable at rest. Class IV (worst): Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. A shift from a higher class (e.g. Class IV) to a lower class (e.g. Class II) indicates an improvement in patient health and functional status. |
| Change in Patient 6-minute Walk Distance (Patient Functional Status) at 6 and 24 Months | Screening, Month 6 (180 days) and Month 24 (after FU completion) | For the 6-minute walk test, the patient is asked to walk for 6 minutes. The total distance walked is measured. Values in the table were calculated as the value at Month 6 (180 days) minus Screening and at Month 24 (after FU completion) minus Screening. A positive change in 6-minute walk distance indicates an improvement in health and functional status. |
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score at 6 and 24 Months | Screening, Month 6 (180 days) and Month 24 (after follow-up (FU) completion) | The KCCQ is a self-evaluation questionnaire for patients with heart failure to assess the severity of their symptoms how it may affect their lives. Scores range between 0 (worst) - 100 (best). Values in the table were calculated as the value at Month 6 (180 days) minus Screening and at Month 24 (after FU completion) minus Screening. The positive change in KCCQ score indicates an improvement in patient Quality of Life. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HW005 Ventricular Assist System Implant of the HW005 Ventricular Assist System.: The HW005 Pump is an implantable centrifugal pump that was designed to provide flows up to 10 L/min. It is a small device which is both lightweight and simple to use. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | HW005 Ventricular Assist System |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Clinical Summary Score | 56.4 units on a scale STANDARD_DEVIATION 33.89 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Overall Summary Score | 45.5 units on a scale STANDARD_DEVIATION 28.44 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Physical Limitation | 45.0 units on a scale STANDARD_DEVIATION 31.69 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Quality of Life | 31.9 units on a scale STANDARD_DEVIATION 27.09 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Self-Efficacy | 75.0 units on a scale STANDARD_DEVIATION 22.36 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Social Limitation | 9.4 units on a scale STANDARD_DEVIATION 13.26 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Symptom Burden | 69.4 units on a scale STANDARD_DEVIATION 38.97 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Symptom Frequency | 66.0 units on a scale STANDARD_DEVIATION 39.91 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Symptom Stability | 37.5 units on a scale STANDARD_DEVIATION 26.22 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) scores KCCQ Total Symptom Score | 67.7 units on a scale STANDARD_DEVIATION 39.32 |
| New York Heart Association (NYHA) Classification Class I | 0 Participants |
| New York Heart Association (NYHA) Classification Class II | 0 Participants |
| New York Heart Association (NYHA) Classification Class III | 3 Participants |
| New York Heart Association (NYHA) Classification Class IV | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
| Six-Minute Walk Test | 135.8 meters STANDARD_DEVIATION 160.12 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 5 / 6 |
Outcome results
Primary
Number of Participants Alive on the Implanted HW005 Ventricular Assist System or Transplanted or Explanted for Recovery at 180 Days
The primary endpoint is success at 180 days which is defined as alive on the originally implanted HW005 Ventricular Assist System or transplanted or explanted for recovery. Patients must survive 60 days post-explant for recovery to be considered successful.
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HW005 Ventricular Assist System | Number of Participants Alive on the Implanted HW005 Ventricular Assist System or Transplanted or Explanted for Recovery at 180 Days | 6 Participants |
Secondary
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score at 6 and 24 Months
The KCCQ is a self-evaluation questionnaire for patients with heart failure to assess the severity of their symptoms how it may affect their lives. Scores range between 0 (worst) - 100 (best). Values in the table were calculated as the value at Month 6 (180 days) minus Screening and at Month 24 (after FU completion) minus Screening. The positive change in KCCQ score indicates an improvement in patient Quality of Life.
Time frame: Screening, Month 6 (180 days) and Month 24 (after follow-up (FU) completion)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HW005 Ventricular Assist System | Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score at 6 and 24 Months | Month 6 | 22.2 score on a scale | Standard Deviation 12.55 |
| HW005 Ventricular Assist System | Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score at 6 and 24 Months | Month 24 | 19.4 score on a scale | Standard Deviation 11.39 |
95% CI: [7.5, 31.4]
Secondary
Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months
The New York Heart Association (NYHA) Functional Classification places patients with heart failure in one of four categories based on how much they are limited during physical activity. Class I (best): No limitation of physical activity. Class II: Slight limitation of physical activity. Comfortable at rest. Class III: Marked limitation of physical activity. Comfortable at rest. Class IV (worst): Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. A shift from a higher class (e.g. Class IV) to a lower class (e.g. Class II) indicates an improvement in patient health and functional status.
Time frame: Screening, Month 6 (180 days) and Month 24 (after FU completion)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Screening | Class I | 0 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Screening | Class II | 0 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Screening | Class III | 3 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Screening | Class IV | 3 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 6 | Class I | 1 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 6 | Class II | 5 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 6 | Class III | 0 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 6 | Class IV | 0 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 24 | Class I | 2 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 24 | Class II | 3 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 24 | Class III | 1 Participants |
| HW005 Ventricular Assist System | Change in NYHA Patient Classification (Patient Functional Status) at 6 and 24 Months | Month 24 | Class IV | 0 Participants |
Secondary
Change in Patient 6-minute Walk Distance (Patient Functional Status) at 6 and 24 Months
For the 6-minute walk test, the patient is asked to walk for 6 minutes. The total distance walked is measured. Values in the table were calculated as the value at Month 6 (180 days) minus Screening and at Month 24 (after FU completion) minus Screening. A positive change in 6-minute walk distance indicates an improvement in health and functional status.
Time frame: Screening, Month 6 (180 days) and Month 24 (after FU completion)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HW005 Ventricular Assist System | Change in Patient 6-minute Walk Distance (Patient Functional Status) at 6 and 24 Months | Month 6 | 198.2 Meters | Standard Deviation 217.01 |
| HW005 Ventricular Assist System | Change in Patient 6-minute Walk Distance (Patient Functional Status) at 6 and 24 Months | Month 24 | 130.0 Meters | Standard Deviation 275.32 |
95% CI: [-158.9, 418.9]
Secondary
Incidence of All Device Failures and Device Malfunctions.
The device failures and malfunctions are the failures on pumping function due to thrombosis inside/outside of the implanted pump, the mechanical failures of the implanted components, the mechanical failures of the external components and the failures due to the user. Events were categorized using the J-MACS definitions.
Time frame: Through study completion, an average of 44.5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HW005 Ventricular Assist System | Incidence of All Device Failures and Device Malfunctions. | 1.66 event rate per patient year |
Secondary
Incidence of All Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs)
SAEs are defined as events that result in death, are life-threatening, result in permanent disability, require medical treatment to prevent permanent disability or require surgical intervention or hospitalization. UADEs are defined as any serious adverse device effect which by its nature, incidence, severity or outcome has not been identified in the current version of the risk analysis report. Events were categorized using the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) definitions.
Time frame: Through study completion, an average of 44.5 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HW005 Ventricular Assist System | Incidence of All Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) | J-MACS SAEs | 1.24 event rate per patient year |
| HW005 Ventricular Assist System | Incidence of All Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) | UADEs | 0 event rate per patient year |
Secondary
Number of Participants Alive on the Implanted HW005 Ventricular Assist System at 180 Days
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HW005 Ventricular Assist System | Number of Participants Alive on the Implanted HW005 Ventricular Assist System at 180 Days | 6 Participants |