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)

Overview

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.

Interventions

• 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.

Primary outcome measures

• All-cause mortality rate [Time frame: Through 24 months when the last subject completes 12 months of follow-up]
• Number of urgent ECMO implantation [Time frame: Through 24 months when the last subject completes 12 months of follow-up]
• Number of urgent heart transplantation [Time frame: Through 24 months when the last subject completes 12 months of follow-up]
• Number of LVAD implantation [Time frame: Through 24 months when the last subject completes 12 months of follow-up]
• Number of unplanned hospitalization for heart failure [Time frame: Through 24 months when the last subject completes 12 months of follow-up]
• Quality of life assessed by KCCQ score [Time frame: Through 24 months when the last subject completes 12 months of follow-up]
• Distance in meters at 6-min walking test [Time frame: Through 24 months when the last subject completes 12 months of follow-up]

Secondary outcome measures (12)

• 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 8 centers

• CHU Besançon — Besançon
• Hôpital Pneumologique et Cardiovasculaire Louis Pradel — Bron
• CHU Caen — Caen
• La Tronche Hospital / CHU Grenoble — La Tronche
• Arnaud de Villeneuve Hospital / CHU Montpellier — Montpellier
• CHU Rouen — Rouen
• CHU Tours — Tours
• CHRU, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu — Vandœuvre-lès-Nancy

Identifiers

NCT: NCT04768322 · 69HCL20_0072 · ID-RCB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗