LVAD Versus GDMT in Ambulatory Advanced Heart Failure Patients (AMBU-VAD)

Left Ventricular Assist Device (LVAD) Versus Guideline Recommended Medical Therapy in Ambulatory Advanced Heart Failure Patients (GDMT)

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 Overview

• Status: Recruiting
• Conditions: End-stage Heart Failure
• Intervention / Treatment: Device: HeartMate 3 TM Left Ventricular Assist System; Other: Guideline Directed Medical Therapy

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume BAUDRY, Dr; Phone Number: +33 383157331; Email: g.baudry@chru-nancy.fr
• Study Contact Backup: Name: Géraldine SAMSON; Email: geraldine.samson@chu-lyon.fr

Study Locations

• France
  • Besançon, France
    • Recruiting
    • CHU Besançon
    • Contact: MARIE FRANCE SERONDE, Pr
    • Principal Investigator: MARIE FRANCE SERONDE, Pr
  • Bron, France
    • Recruiting
    • Hôpital Pneumologique et Cardiovasculaire Louis Pradel
    • Contact: MATTEO POZZI, Dr; Phone Number: +33 4 72 35 71 49; Email: matteo.pozzi@chu-lyon.fr
  • Caen, France
    • Recruiting
    • CHU Caen
    • Contact: KATRIEN DR BLANCHART, Dr
    • Principal Investigator: KATRIEN DR BLANCHART, Dr
  • La Tronche, France
    • Recruiting
    • La Tronche Hospital / CHU Grenoble
    • Contact: AUDE BOIGNARD; Email: aboignard@chu-grenoble.fr
    • Principal Investigator: AUDE BOIGNARD, Dr
  • Montpellier, France
    • Recruiting
    • Arnaud de Villeneuve Hospital / CHU Montpellier
    • Principal Investigator: PASCAL BAPTISTELLA, Dr
    • Contact: Valentin DUPASQUIER; Email: valentin.dupasquier@chu-montpellier.fr
  • Rouen, France
    • Recruiting
    • CHU Rouen
    • Principal Investigator: FABRICE BAUER
    • Contact: FABRICE BAUER
  • Tours, France
    • Recruiting
    • CHU Tours
    • Contact: Thierry BOURGUIGNON, Dr
    • Principal Investigator: Thierry BOURGUIGNON
  • Vandœuvre-lès-Nancy, France
    • Recruiting
    • CHRU, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu
    • Contact: GUILLAUME BAUDRY; Phone Number: 33 3 83 15 73 31; Email: g.baudry@chru-nancy.fr
    • Principal Investigator: GUILLAUME BAUDRY, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All patients ≥18 years,

2. End-stage heart failure, evaluated by the local Heart Team, defined as:

   • 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
   • Receiving medical management with optimal doses of betablockers, Angiotensin-Converting-Enzyme-inhibitors or Angiotensin II Receptor Blockers or angiotensin receptor neprilysin inhibitor (if eligible) and Mineralocorticoid Receptor Antagonists and Sodium-GLucose co-Transporter-2 (SGLT2) inhibitors for at least 45 days if tolerated according to guideline at maximal tolerated dose (if maximal HF drug dosage is not reached the investigators will have to explain reason behind not maximal dosage).
   • Receiving Cardiac Resynchronization Therapy and or Implantable Cardioverter Defibrillators if indicated for at least 45 days and
   • No mechanical circulatory support or inotrope therapy since > 30 days,
3. Having a health coverage,
4. Signed written informed consent,
5. Patient without any legal protection measure.

Exclusion Criteria:

1. Inotrope dependent patients or existence of ongoing mechanical circulatory support (MCS) in the last 30 days,
2. Right ventricular dysfunction (heart team consensus) with the expected need of Bi-VAD support,
3. Female patients currently pregnant or women of childbearing age who were not using contraception,
4. Active infection,
5. Irreversible end-organ dysfunction prior to LVAD implantation,
6. Contraindication to anti-coagulant or anti-platelet therapies,
7. History of any organ transplant prior to inclusion,
8. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues likely to impair compliance,
9. Frailty according to heart team,
10. Platelet count < 100,000 x 103/liter (<100,000/ml)
11. Body Surface Area (BSA) < 1.2 m2,
12. Any condition other than heart failure that could limit survival to less than 24 months,
13. Chronic renal insufficiency (GFR definitely <30 ml/min) or hepatic cirrhosis,
14. Participation in any other interventional clinical investigation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Left Ventricular Assist Device and Guideline Directed Medical Therapy; The intervention group will receive an early left ventricular assist device implantation (bridge to transplantation, bridge to candidacy or destination therapy) in addition to guideline directed medical therapy within 21 days of randomization.	Device: HeartMate 3 TM Left Ventricular Assist System; The HeartMate 3 TM Left Ventricular Assist System will be implanted within 21 days of randomization.; Other: Guideline Directed Medical Therapy; 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.
Other: Guideline Directed Medical Therapy; 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.	Other: Guideline Directed Medical Therapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	Through 24 months when the last subject completes 12 months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AEs)		at 1 month
Number of adverse events (AEs)		at 3 months
Number of adverse events (AEs)		at 6 months
Number of adverse events (AEs)		at 12 months
Number of adverse events (AEs)		at 18 months
Number of adverse events (AEs)		at 24 months
All-cause mortality rate		at 1 month
All-cause mortality rate		at 3 months
All-cause mortality rate		at 6 months
All-cause mortality rate		at 12 months
All-cause mortality rate		at 18 months
All-cause mortality rate		at 24 months
number of ECMO implantation		at 1 month
number of ECMO implantation		at 3 months
number of ECMO implantation		at 6 months
number of ECMO implantation		at 12 months
number of ECMO implantation		at 18 months
number of ECMO implantation		at 24 months
number of urgent heart transplantation		at 1 month
number of urgent heart transplantation		at 3 months
number of urgent heart transplantation		at 12 months
number of urgent heart transplantation		at 18 months
number of urgent heart transplantation		at 24 months
VAD implantation rate		at 1 month
VAD implantation rate		at 3 months
VAD implantation rate		at 6 months
VAD implantation rate		at 12 months
VAD implantation rate		at 18 months
VAD implantation rate		at 24 months
Unplanned hospitalization for heart failure rate		at 1 month
Unplanned hospitalization for heart failure rate		at 3 months
Unplanned hospitalization for heart failure rate		at 6 months
Unplanned hospitalization for heart failure rate		at 12 months
Unplanned hospitalization for heart failure rate		at 18 months
Unplanned hospitalization for heart failure rate		at 24 months
Recurrent hospitalizations rate	Defined as total number of hospitalizations	at 1 month
Recurrent hospitalizations rate	Defined as total number of hospitalizations	at 3 months
Recurrent hospitalizations rate	Defined as total number of hospitalizations	at 6 months
Recurrent hospitalizations rate	Defined as total number of hospitalizations	at 12 months
Recurrent hospitalizations rate	Defined as total number of hospitalizations	at 18 months
Recurrent hospitalizations rate	Defined as total number of hospitalizations	at 24 months
Number of patients with a persistence of the eligibility to LVAD implantation	In the GDMT group only	at 12 and 24 months
Number of patients with a persistence of the eligibility to LVAD implantation	In the GDMT group only	at 12 months
Number of days alive out of hospital		at 24 months
New York Heart Association (NYHA) status		at inclusion
New York Heart Association (NYHA) status		at 1 month
New York Heart Association (NYHA) status		at 3 months
New York Heart Association (NYHA) status		at 6 months
New York Heart Association (NYHA) status		at 12 months
New York Heart Association (NYHA) status		at 18 months
New York Heart Association (NYHA) status		at 24 months
Distance in meters at 6-min walking test		at inclusion
Distance in meters at 6-min walking test		at 3 months
Distance in meters at 6-min walking test		at 6 months
Distance in meters at 6-min walking test		at 12 months
Distance in meters at 6-min walking test		at 18 months
Distance in meters at 6-min walking test		at 24 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score		at inclusion
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score		at 3 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score		at 6 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score		at 12 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score		at 18 months
Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score		at 24 months
Quality of life assessed by KCCQ score		at inclusion
Quality of life assessed by KCCQ score		at 3 months
Quality of life assessed by KCCQ score		at 6 months
Quality of life assessed by KCCQ score		at 12 months
Quality of life assessed by KCCQ score		at 18 months
Quality of life assessed by KCCQ score		at 24 months
Right ventricular function assessed by echocardiographic parameters		at inclusion
Right ventricular function assessed by echocardiographic parameters		at 3 months
Right ventricular function assessed by echocardiographic parameters		at 6 months
Right ventricular function assessed by echocardiographic parameters		at 12 months
Right ventricular function assessed by echocardiographic parameters		at 18 months
Right ventricular function assessed by echocardiographic parameters		at 24 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate		at inclusion
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate		at 3 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate		at 6 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate		at 12 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate		at 18 months
Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate		at 24 months
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)		at inclusion
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)		at 1 month
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)		at 6 months
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)		at 12 months
Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)		at 24 months
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)		at inclusion
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)		at 1 month
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)		at 6 months
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)		at 12 months
Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)		at 24 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)		at inclusion
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)		at 1 month
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)		at 3 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)		at 12 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)		at 18 months
Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)		at 24 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Guillaume BAUDRY, Dr, CHRU Nancy

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Left Ventricular Assist Device; Heart Surgery; Guideline Directed Medical Therapy; End-stage; Not inotrope-dependent; HeartMate 3 system
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 69HCL20_0072; ID-RCB (Other Identifier: 2025-A02239-40)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No