LVAD Versus GDMT in Ambulatory Advanced Heart Failure Patients

NCT04768322 | Recruiting DMC

• 2 other identifiers: 69HCL20_0072ID-RCB
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 8

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.

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

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (97)

• 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

Study Arms (2)

Early Left Ventricular Assist Device and Guideline Directed Medical Therapy

EXPERIMENTAL

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; Other: Guideline Directed Medical Therapy

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.

Other: Guideline Directed Medical Therapy

Interventions

HeartMate 3 TM Left Ventricular Assist System DEVICE

The HeartMate 3 TM Left Ventricular Assist System will be implanted within 21 days of randomization.

Early Left Ventricular Assist Device and Guideline Directed Medical Therapy

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.

Early Left Ventricular Assist Device and Guideline Directed Medical Therapy; Guideline Directed Medical Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (8)

CHU Besançon

Besançon, France

RECRUITING

Hôpital Pneumologique et Cardiovasculaire Louis Pradel

Bron, France

RECRUITING

CHU Caen

Caen, France

RECRUITING

La Tronche Hospital / CHU Grenoble

La Tronche, France

RECRUITING

Arnaud de Villeneuve Hospital / CHU Montpellier

Montpellier, France

RECRUITING

CHU Rouen

Rouen, France

RECRUITING

CHU Tours

Tours, France

RECRUITING

CHRU, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu

Vandœuvre-lès-Nancy, France

RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Guillaume BAUDRY, Dr

  CHRU Nancy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillaume BAUDRY, Dr

CONTACT

383157331; g.baudry@chru-nancy.fr

Géraldine SAMSON

CONTACT

geraldine.samson@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 24, 2021
• Study Start: February 24, 2021
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)