Clinical trial NCT04768322: LVAD Versus GDMT in Ambulatory Advanced Heart Failure Patients
Official title: Left Ventricular Assist Device (LVAD) Versus Guideline Recommended Medical Therapy in Ambulatory Advanced Heart Failure Patients (GDMT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: End-stage Heart Failure
Keywords: Heart Failure
End-stage
Not inotrope-dependent
Left Ventricular Assist Device
HeartMate 3 system
Heart Surgery
Guideline Directed Medical Therapy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2021-02-24
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Primary outcomes:
measure: All-cause mortality rate
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
measure: Number of urgent ECMO implantation
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
measure: Number of urgent heart transplantation
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
measure: Number of LVAD implantation
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
measure: Number of unplanned hospitalization for heart failure
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
measure: Quality of life assessed by KCCQ score
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
measure: Distance in meters at 6-min walking test
timeFrame: Through 24 months when the last subject completes 12 months of follow-up
Secondary outcomes:
measure: Number of adverse events (AEs)
timeFrame: at 1 month
measure: Number of adverse events (AEs)
timeFrame: at 3 months
measure: Number of adverse events (AEs)
timeFrame: at 6 months
measure: Number of adverse events (AEs)
timeFrame: at 12 months
measure: Number of adverse events (AEs)
timeFrame: at 18 months
measure: Number of adverse events (AEs)
timeFrame: at 24 months
measure: All-cause mortality rate
timeFrame: at 1 month
measure: All-cause mortality rate
timeFrame: at 3 months
measure: All-cause mortality rate
timeFrame: at 6 months
measure: All-cause mortality rate
timeFrame: at 12 months
measure: All-cause mortality rate
timeFrame: at 18 months
measure: All-cause mortality rate
timeFrame: at 24 months
measure: number of ECMO implantation
timeFrame: at 1 month
measure: number of ECMO implantation
timeFrame: at 3 months
measure: number of ECMO implantation
timeFrame: at 6 months
measure: number of ECMO implantation
timeFrame: at 12 months
measure: number of ECMO implantation
timeFrame: at 18 months
measure: number of ECMO implantation
timeFrame: at 24 months
measure: number of urgent heart transplantation
timeFrame: at 1 month
measure: number of urgent heart transplantation
timeFrame: at 3 months
measure: number of urgent heart transplantation
timeFrame: at 12 months
measure: number of urgent heart transplantation
timeFrame: at 18 months
measure: number of urgent heart transplantation
timeFrame: at 24 months
measure: VAD implantation rate
timeFrame: at 1 month
measure: VAD implantation rate
timeFrame: at 3 months
measure: VAD implantation rate
timeFrame: at 6 months
measure: VAD implantation rate
timeFrame: at 12 months
measure: VAD implantation rate
timeFrame: at 18 months
measure: VAD implantation rate
timeFrame: at 24 months
measure: Unplanned hospitalization for heart failure rate
timeFrame: at 1 month
measure: Unplanned hospitalization for heart failure rate
timeFrame: at 3 months
measure: Unplanned hospitalization for heart failure rate
timeFrame: at 6 months
measure: Unplanned hospitalization for heart failure rate
timeFrame: at 12 months
measure: Unplanned hospitalization for heart failure rate
timeFrame: at 18 months
measure: Unplanned hospitalization for heart failure rate
timeFrame: at 24 months
measure: Recurrent hospitalizations rate
timeFrame: at 1 month
measure: Recurrent hospitalizations rate
timeFrame: at 3 months
measure: Recurrent hospitalizations rate
timeFrame: at 6 months
measure: Recurrent hospitalizations rate
timeFrame: at 12 months
measure: Recurrent hospitalizations rate
timeFrame: at 18 months
measure: Recurrent hospitalizations rate
timeFrame: at 24 months
measure: Number of patients with a persistence of the eligibility to LVAD implantation
timeFrame: at 12 and 24 months
measure: Number of patients with a persistence of the eligibility to LVAD implantation
timeFrame: at 12 months
measure: Number of days alive out of hospital
timeFrame: at 24 months
measure: New York Heart Association (NYHA) status
timeFrame: at inclusion
measure: New York Heart Association (NYHA) status
timeFrame: at 1 month
measure: New York Heart Association (NYHA) status
timeFrame: at 3 months
measure: New York Heart Association (NYHA) status
timeFrame: at 6 months
measure: New York Heart Association (NYHA) status
timeFrame: at 12 months
measure: New York Heart Association (NYHA) status
timeFrame: at 18 months
measure: New York Heart Association (NYHA) status
timeFrame: at 24 months
measure: Distance in meters at 6-min walking test
timeFrame: at inclusion
measure: Distance in meters at 6-min walking test
timeFrame: at 3 months
measure: Distance in meters at 6-min walking test
timeFrame: at 6 months
measure: Distance in meters at 6-min walking test
timeFrame: at 12 months
measure: Distance in meters at 6-min walking test
timeFrame: at 18 months
measure: Distance in meters at 6-min walking test
timeFrame: at 24 months
measure: Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
timeFrame: at inclusion
measure: Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
timeFrame: at 3 months
measure: Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
timeFrame: at 6 months
measure: Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
timeFrame: at 12 months
measure: Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
timeFrame: at 18 months
measure: Quality of life assessed by European Quality of Life-5 Dimensions (EQ-5D) questionnaire score
timeFrame: at 24 months
measure: Quality of life assessed by KCCQ score
timeFrame: at inclusion
measure: Quality of life assessed by KCCQ score
timeFrame: at 3 months
measure: Quality of life assessed by KCCQ score
timeFrame: at 6 months
measure: Quality of life assessed by KCCQ score
timeFrame: at 12 months
measure: Quality of life assessed by KCCQ score
timeFrame: at 18 months
measure: Quality of life assessed by KCCQ score
timeFrame: at 24 months
measure: Right ventricular function assessed by echocardiographic parameters
timeFrame: at inclusion
measure: Right ventricular function assessed by echocardiographic parameters
timeFrame: at 3 months
measure: Right ventricular function assessed by echocardiographic parameters
timeFrame: at 6 months
measure: Right ventricular function assessed by echocardiographic parameters
timeFrame: at 12 months
measure: Right ventricular function assessed by echocardiographic parameters
timeFrame: at 18 months
measure: Right ventricular function assessed by echocardiographic parameters
timeFrame: at 24 months
measure: Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
timeFrame: at inclusion
measure: Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
timeFrame: at 3 months
measure: Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
timeFrame: at 6 months
measure: Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
timeFrame: at 12 months
measure: Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
timeFrame: at 18 months
measure: Heart failure assessed by N Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) rate
timeFrame: at 24 months
measure: Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
timeFrame: at inclusion
measure: Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
timeFrame: at 1 month
measure: Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
timeFrame: at 6 months
measure: Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
timeFrame: at 12 months
measure: Cardio-renal syndrome assessed by rates of Soluble urokinase-type Plasminogen Activator Receptor (SuPAR)
timeFrame: at 24 months
measure: Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
timeFrame: at inclusion
measure: Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
timeFrame: at 1 month
measure: Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
timeFrame: at 6 months
measure: Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
timeFrame: at 12 months
measure: Cardio-renal syndrome assessed by rates of Interleukin-6 (IL-6)
timeFrame: at 24 months
measure: Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
timeFrame: at inclusion
measure: Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
timeFrame: at 1 month
measure: Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
timeFrame: at 3 months
measure: Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
timeFrame: at 12 months
measure: Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
timeFrame: at 18 months
measure: Cardio-renal syndrome assessed by rates of Kidney Injury Molecule-1 (KIM1)
timeFrame: at 24 months
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU Besançon
city: Bron
country: France
facility: Hôpital Pneumologique et Cardiovasculaire Louis Pradel
city: Caen
country: France
facility: CHU Caen
city: La Tronche
country: France
facility: La Tronche Hospital / CHU Grenoble
city: Montpellier
country: France
facility: Arnaud de Villeneuve Hospital / CHU Montpellier
city: Rouen
country: France
facility: CHU Rouen
city: Tours
country: France
facility: CHU Tours
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu
Study officials:
affiliation: CHRU Nancy
name: Guillaume BAUDRY, Dr
role: PRINCIPAL_INVESTIGATOR
References: