Heart failure is a severe disease affecting approximately 1-2% of the adult population in developed countries and around 26 million people worldwide. Up to 10% of these patients are in advanced stage heart failure, which is defined by a significant morbimortality and considerable medical expenses. Despite advances in its medical management, advanced (or end stage) heart failure is characterized by refractoriness to conventional therapies including guideline-directed pharmacological and non-surgical device treatments. These patients remain severely symptomatic (NYHA IV) and have objective signs of congestion or low cardiac output. Left ventricular assist devices (LVADs) have been used in patients with heart failure with reduced ejection fraction for almost 20 years either as an alternative or a bridge to heart transplantation. LVADs improve heart failure symptoms and survival at the cost of increased rates of infection, stroke and bleeding. Despite the lack of evidence, LVAD implantation in ambulatory patients is not rare, with INTERMACS profiles ≥4 patients representing 15.7% of the overall population implanted between 2012 and 2016. The aim of this study is to investigate the efficacy and safety of left ventricular assist devices compared to traditional HF medical treatment alone in a population of ambulatory advanced heart failure patients. Secondary objectives are to better identify subgroups of patients that would benefit the most from the implantation of an LVAD as well as to assess the optimal timing of intervention.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
The HeartMate 3 TM Left Ventricular Assist System will be implanted within 21 days of randomization.
Patients randomized in the control group will continue their guideline directed medical therapy which comprises the following stable combination at the maximal tolerated dose of betablockers, Angiotensin-Converting-Enzyme-inhibitors or Angiotensin II Receptor Blockers or Angiotensin receptor Neprilysin inhibitor and Mineralocorticoid Receptor Antagonists and Sodium-GLucose co-Transporter-2 (SGLT2) inhibitors if tolerated.
CHU Besançon
Besançon, France
RECRUITINGHôpital Pneumologique et Cardiovasculaire Louis Pradel
Bron, France
RECRUITINGCHU Caen
Caen, France
RECRUITINGLa Tronche Hospital / CHU Grenoble
La Tronche, France
RECRUITINGArnaud de Villeneuve Hospital / CHU Montpellier
Montpellier, France
RECRUITINGCHU Rouen
Rouen, France
RECRUITINGCHU Tours
Tours, France
RECRUITINGCHRU, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu
Vandœuvre-lès-Nancy, France
RECRUITINGAll-cause mortality rate
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Number of urgent ECMO implantation
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Number of urgent heart transplantation
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Number of LVAD implantation
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Number of unplanned hospitalization for heart failure
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Quality of life assessed by KCCQ score
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Distance in meters at 6-min walking test
The composite of 5 clinical endpoints is using a win ratio concept. Mortality has higher priority than Urgent ECMO implantation, urgent heart transplantation or LVAD implantation, unplanned hospitalization for heart failure, improvement of KCCQ by at least 5points, improvement of 6-minute walk test distance by at least 75 meters. Our main approach uses matched pairs of patients. Each pair is 'untied' first on the basis of the most important event (death) and secondly (if necessary) on the lesser event. The numbers of pairs in which the patient on new treatment 'won' and 'lost' are compared to produce the 'win ratio'. The 95% CI and P-value for the win ratio are readily obtained.
Time frame: Through 24 months when the last subject completes 12 months of follow-up
Number of adverse events (AEs)
Time frame: at 1 month
Number of adverse events (AEs)
Time frame: at 3 months
Number of adverse events (AEs)
Time frame: at 6 months
Number of adverse events (AEs)
Time frame: at 12 months
Number of adverse events (AEs)
Time frame: at 18 months
Number of adverse events (AEs)
Time frame: at 24 months
All-cause mortality rate
Time frame: at 1 month
All-cause mortality rate
Time frame: at 3 months
All-cause mortality rate
Time frame: at 6 months
All-cause mortality rate
Time frame: at 12 months
All-cause mortality rate
Time frame: at 18 months
All-cause mortality rate
Time frame: at 24 months
number of ECMO implantation
Time frame: at 1 month
number of ECMO implantation
Time frame: at 3 months
number of ECMO implantation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: at 6 months
number of ECMO implantation
Time frame: at 12 months
number of ECMO implantation
Time frame: at 18 months
number of ECMO implantation
Time frame: at 24 months
number of urgent heart transplantation
Time frame: at 1 month
number of urgent heart transplantation
Time frame: at 3 months
number of urgent heart transplantation
Time frame: at 12 months
number of urgent heart transplantation
Time frame: at 18 months
number of urgent heart transplantation
Time frame: at 24 months
VAD implantation rate
Time frame: at 1 month
VAD implantation rate
Time frame: at 3 months
VAD implantation rate
Time frame: at 6 months
VAD implantation rate
Time frame: at 12 months
VAD implantation rate
Time frame: at 18 months
VAD implantation rate
Time frame: at 24 months
Unplanned hospitalization for heart failure rate
Time frame: at 1 month
Unplanned hospitalization for heart failure rate
Time frame: at 3 months
Unplanned hospitalization for heart failure rate
Time frame: at 6 months
Unplanned hospitalization for heart failure rate
Time frame: at 12 months
Unplanned hospitalization for heart failure rate
Time frame: at 18 months
Unplanned hospitalization for heart failure rate
Time frame: at 24 months
Recurrent hospitalizations rate
Defined as total number of hospitalizations
Time frame: at 1 month
Recurrent hospitalizations rate
Defined as total number of hospitalizations
Time frame: at 3 months
Recurrent hospitalizations rate
Defined as total number of hospitalizations
Time frame: at 6 months
Recurrent hospitalizations rate
Defined as total number of hospitalizations
Time frame: at 12 months
Recurrent hospitalizations rate
Defined as total number of hospitalizations
Time frame: at 18 months
Recurrent hospitalizations rate
Defined as total number of hospitalizations
Time frame: at 24 months
Number of patients with a persistence of the eligibility to LVAD implantation
In the GDMT group only
Time frame: at 12 and 24 months
Number of patients with a persistence of the eligibility to LVAD implantation
In the GDMT group only
Time frame: at 12 months
Number of days alive out of hospital
Time frame: at 24 months
New York Heart Association (NYHA) status
Time frame: at inclusion
New York Heart Association (NYHA) status
Time frame: at 1 month
New York Heart Association (NYHA) status
Time frame: at 3 months
New York Heart Association (NYHA) status
Time frame: at 6 months
New York Heart Association (NYHA) status
Time frame: at 12 months
New York Heart Association (NYHA) status
Time frame: at 18 months
New York Heart Association (NYHA) status
Time frame: at 24 months
Distance in meters at 6-min walking test
Time frame: at inclusion
Distance in meters at 6-min walking test
Time frame: at 3 months
Distance in meters at 6-min walking test
Time frame: at 6 months
Distance in meters at 6-min walking test
Time frame: at 12 months
Distance in meters at 6-min walking test
Time frame: at 18 months
Distance in meters at 6-min walking test
Time frame: at 24 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
Time frame: at inclusion
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
Time frame: at 3 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
Time frame: at 6 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
Time frame: at 12 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
Time frame: at 18 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
Time frame: at 24 months
Quality of life assessed by KCCQ score
Time frame: at inclusion
Quality of life assessed by KCCQ score
Time frame: at 3 months
Quality of life assessed by KCCQ score
Time frame: at 6 months
Quality of life assessed by KCCQ score
Time frame: at 12 months
Quality of life assessed by KCCQ score
Time frame: at 18 months
Quality of life assessed by KCCQ score
Time frame: at 24 months
Right ventricular function assessed by echocardiographic parameters
Time frame: at inclusion
Right ventricular function assessed by echocardiographic parameters
Time frame: at 3 months
Right ventricular function assessed by echocardiographic parameters
Time frame: at 6 months
Right ventricular function assessed by echocardiographic parameters
Time frame: at 12 months
Right ventricular function assessed by echocardiographic parameters
Time frame: at 18 months
Right ventricular function assessed by echocardiographic parameters
Time frame: at 24 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
Time frame: at inclusion
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
Time frame: at 3 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
Time frame: at 6 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
Time frame: at 12 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
Time frame: at 18 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
Time frame: at 24 months
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
Time frame: at inclusion
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
Time frame: at 1 month
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
Time frame: at 6 months
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
Time frame: at 12 months
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
Time frame: at 24 months
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
Time frame: at inclusion
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
Time frame: at 1 month
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
Time frame: at 6 months
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
Time frame: at 12 months
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
Time frame: at 24 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
Time frame: at inclusion
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
Time frame: at 1 month
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
Time frame: at 3 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
Time frame: at 12 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
Time frame: at 18 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
Time frame: at 24 months