Skip to main content
OpenTrials
Recruiting

NCT Number: NCT04768322

LVAD Versus GDMT in Ambulatory Advanced Heart Failure Patients

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

End-stage Heart Failure Cardiovascular Diseases Heart Diseases Heart Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU Besançon, Besançon, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • All patients ≥18 years,
  • 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,
  • Having a health coverage,
  • Signed written informed consent,
  • Patient without any legal protection measure.

Exclusion criteria

  • 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,
  • Irreversible end-organ dysfunction prior to LVAD implantation,
  • Contraindication to anti-coagulant or anti-platelet therapies,
  • History of any organ transplant prior to inclusion,
  • Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues likely to impair compliance,
  • Frailty according to heart team,
  • Platelet count < 100,000 x 103/liter (<100,000/ml)
  • Body Surface Area (BSA) < 1.2 m2,
  • Any condition other than heart failure that could limit survival to less than 24 months,
  • Chronic renal insufficiency (GFR definitely <30 ml/min) or hepatic cirrhosis,
  • Participation in any other interventional clinical investigation.

Treatment and study plan

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

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.

Primary outcomes

  1. All-cause mortality rate

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

  2. Number of urgent ECMO implantation

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

  3. Number of urgent heart transplantation

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

  4. Number of LVAD implantation

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

  5. Number of unplanned hospitalization for heart failure

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

  6. Quality of life assessed by KCCQ score

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

  7. Distance in meters at 6-min walking test

    Time frame: Through 24 months when the last subject completes 12 months of follow-up

    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.

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

  5. Number of adverse events (AEs)

    Time frame: at 18 months

  6. Number of adverse events (AEs)

    Time frame: at 24 months

  7. All-cause mortality rate

    Time frame: at 1 month

  8. All-cause mortality rate

    Time frame: at 3 months

  9. All-cause mortality rate

    Time frame: at 6 months

  10. All-cause mortality rate

    Time frame: at 12 months

  11. All-cause mortality rate

    Time frame: at 18 months

  12. All-cause mortality rate

    Time frame: at 24 months

  13. number of ECMO implantation

    Time frame: at 1 month

  14. number of ECMO implantation

    Time frame: at 3 months

  15. number of ECMO implantation

    Time frame: at 6 months

  16. number of ECMO implantation

    Time frame: at 12 months

  17. number of ECMO implantation

    Time frame: at 18 months

  18. number of ECMO implantation

    Time frame: at 24 months

  19. number of urgent heart transplantation

    Time frame: at 1 month

  20. number of urgent heart transplantation

    Time frame: at 3 months

  21. number of urgent heart transplantation

    Time frame: at 12 months

  22. number of urgent heart transplantation

    Time frame: at 18 months

  23. number of urgent heart transplantation

    Time frame: at 24 months

  24. VAD implantation rate

    Time frame: at 1 month

  25. VAD implantation rate

    Time frame: at 3 months

  26. VAD implantation rate

    Time frame: at 6 months

  27. VAD implantation rate

    Time frame: at 12 months

  28. VAD implantation rate

    Time frame: at 18 months

  29. VAD implantation rate

    Time frame: at 24 months

  30. Unplanned hospitalization for heart failure rate

    Time frame: at 1 month

  31. Unplanned hospitalization for heart failure rate

    Time frame: at 3 months

  32. Unplanned hospitalization for heart failure rate

    Time frame: at 6 months

  33. Unplanned hospitalization for heart failure rate

    Time frame: at 12 months

  34. Unplanned hospitalization for heart failure rate

    Time frame: at 18 months

  35. Unplanned hospitalization for heart failure rate

    Time frame: at 24 months

  36. Recurrent hospitalizations rate

    Time frame: at 1 month

    Defined as total number of hospitalizations

  37. Recurrent hospitalizations rate

    Time frame: at 3 months

    Defined as total number of hospitalizations

  38. Recurrent hospitalizations rate

    Time frame: at 6 months

    Defined as total number of hospitalizations

  39. Recurrent hospitalizations rate

    Time frame: at 12 months

    Defined as total number of hospitalizations

  40. Recurrent hospitalizations rate

    Time frame: at 18 months

    Defined as total number of hospitalizations

  41. Recurrent hospitalizations rate

    Time frame: at 24 months

    Defined as total number of hospitalizations

  42. Number of patients with a persistence of the eligibility to LVAD implantation

    Time frame: at 12 and 24 months

    In the GDMT group only

  43. Number of patients with a persistence of the eligibility to LVAD implantation

    Time frame: at 12 months

    In the GDMT group only

  44. Number of days alive out of hospital

    Time frame: at 24 months

  45. New York Heart Association (NYHA) status

    Time frame: at inclusion

  46. New York Heart Association (NYHA) status

    Time frame: at 1 month

  47. New York Heart Association (NYHA) status

    Time frame: at 3 months

  48. New York Heart Association (NYHA) status

    Time frame: at 6 months

  49. New York Heart Association (NYHA) status

    Time frame: at 12 months

  50. New York Heart Association (NYHA) status

    Time frame: at 18 months

  51. New York Heart Association (NYHA) status

    Time frame: at 24 months

  52. Distance in meters at 6-min walking test

    Time frame: at inclusion

  53. Distance in meters at 6-min walking test

    Time frame: at 3 months

  54. Distance in meters at 6-min walking test

    Time frame: at 6 months

  55. Distance in meters at 6-min walking test

    Time frame: at 12 months

  56. Distance in meters at 6-min walking test

    Time frame: at 18 months

  57. Distance in meters at 6-min walking test

    Time frame: at 24 months

  58. Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score

    Time frame: at inclusion

  59. Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score

    Time frame: at 3 months

  60. Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score

    Time frame: at 6 months

  61. Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score

    Time frame: at 12 months

  62. Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score

    Time frame: at 18 months

  63. Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score

    Time frame: at 24 months

  64. Quality of life assessed by KCCQ score

    Time frame: at inclusion

  65. Quality of life assessed by KCCQ score

    Time frame: at 3 months

  66. Quality of life assessed by KCCQ score

    Time frame: at 6 months

  67. Quality of life assessed by KCCQ score

    Time frame: at 12 months

  68. Quality of life assessed by KCCQ score

    Time frame: at 18 months

  69. Quality of life assessed by KCCQ score

    Time frame: at 24 months

  70. Right ventricular function assessed by echocardiographic parameters

    Time frame: at inclusion

  71. Right ventricular function assessed by echocardiographic parameters

    Time frame: at 3 months

  72. Right ventricular function assessed by echocardiographic parameters

    Time frame: at 6 months

  73. Right ventricular function assessed by echocardiographic parameters

    Time frame: at 12 months

  74. Right ventricular function assessed by echocardiographic parameters

    Time frame: at 18 months

  75. Right ventricular function assessed by echocardiographic parameters

    Time frame: at 24 months

  76. Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate

    Time frame: at inclusion

  77. Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate

    Time frame: at 3 months

  78. Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate

    Time frame: at 6 months

  79. Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate

    Time frame: at 12 months

  80. Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate

    Time frame: at 18 months

  81. Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate

    Time frame: at 24 months

  82. Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)

    Time frame: at inclusion

  83. Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)

    Time frame: at 1 month

  84. Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)

    Time frame: at 6 months

  85. Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)

    Time frame: at 12 months

  86. Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)

    Time frame: at 24 months

  87. Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)

    Time frame: at inclusion

  88. Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)

    Time frame: at 1 month

  89. Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)

    Time frame: at 6 months

  90. Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)

    Time frame: at 12 months

  91. Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)

    Time frame: at 24 months

  92. Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)

    Time frame: at inclusion

  93. Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)

    Time frame: at 1 month

  94. Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)

    Time frame: at 3 months

  95. Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)

    Time frame: at 12 months

  96. Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)

    Time frame: at 18 months

  97. Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)

    Time frame: at 24 months

Study contacts

Contact information is provided by the study sponsor or research team.

Guillaume BAUDRY, Dr

CONTACT

[email protected]

383157331 ext. +33

Géraldine SAMSON

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

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

Acronym: AMBU-VAD

Important dates

Study start
2021
Primary completion
2029
Study completion
2029
First posted
Feb 24, 2021
Registry last updated
May 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.