About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

All patients ≥18 years,

Left ventricular ejection fraction ≤ 35% within 1 week prior to randomization and

Cardiac Index < 2.2 L/min/m² by hemodynamic use within 1 month prior to randomization or VO2 max < 14 ml/kg/min (or <50% of predicted VO2max) within 1 month prior to randomization OR low 6-min walking test (< 420 m) within 1 month prior to randomization or ≥ 2 hospitalizations for heart failure in the past year and

NYHA III-IV (INTERMACS profile 4-6) and and

Disqualifiers

Inotrope dependent patients or existence of ongoing mechanical circulatory support (MCS) in the last 30 days,

Right ventricular dysfunction (heart team consensus) with the expected need of Bi-VAD support,

Female patients currently pregnant or women of childbearing age who were not using contraception,

Active infection,

Trial design

Design model

Parallel

Treatments tested in this trial

HeartMate 3 TM Left Ventricular Assist System
Device
The HeartMate 3 TM Left Ventricular Assist System will be implanted within 21 days of randomization.
Guideline Directed Medical Therapy
Other intervention
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.

Treatment groups

92 Participants

are divided into 2 treatment groups

Group A: Early Left Ventricular Assist Device and Guideline Directed Medical TherapyExperimental treatment 2 interventions

Group B: Guideline Directed Medical TherapyOther 1 intervention

Trial outcomes

Primary outcomes

1

All-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

2

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

3

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

4

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

Secondary outcomes

1

Number of adverse events (AEs)

Time frame

at 1 month

2

Number of adverse events (AEs)

Time frame

at 3 months

3

Number of adverse events (AEs)

Time frame

at 6 months

4

Number of adverse events (AEs)

Time frame

at 12 months

LVAD Versus GDMT in Ambulatory Advanced Heart Failure Patients

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts