Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure

Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure

The purpose of TEAM-HF IDE clinical trial is to evaluate safety and effectiveness of the HeartMate 3 LVAS compared to guideline directed medical therapy (GDMT) in a population of ambulatory advanced heart failure patients who are not dependent on intravenous inotrope.

Patients with heart failure (HF) suffer from a high degree of morbidity and mortality. Left ventricular assist device (LVAD) therapy has become the standard of care for the treatment of advanced HF patients who are deemed to be dependent on continuous intravenous inotropes, extending life expectancy, enhancing overall quality of life, and improving functional capacity. However, use of LVADs in ambulatory, non-inotrope dependent advanced HF population is limited. Elevated mean pulmonary artery pressure (PAP) secondary to left ventricular failure has emerged as a potential predictor of increased mortality risk for patients refractory to maximally tolerated guideline directed medical therapy (GDMT). In these patients, left ventricular failure with elevated mean PAP may represent objective criteria to identify advanced HF patients requiring heart replacement therapies such as LVAD.

The TEAM-HF IDE trial will enroll approximately 850 subjects with New York Heart Association (NYHA) Class IIIB/IV HF who had a prior heart failure hospitalization and an elevated mean PAP secondary to left ventricular failure. Elevated mean PAP will be identified using an implanted PAP monitoring sensor, the CardioMEMS PA Sensor. All subjects enrolled can have a previously implanted CardioMEMS PA Sensor or, if not, will be implanted with the CardioMEMS PA Sensor after enrollment. The overall objectives of TEAM-HF trial are two-fold: 1) To determine whether PAP can objectively identify patients most at risk for worsening HF and therefore most likely to benefit from earlier intervention with LVAD therapy and 2) To determine the benefit of LVAD therapy in non-inotrope advanced HF patients with elevated mean PAP refractory to GDMT.

The trial will include approximately 75 global sites and consists of a Randomized Arm and a Single Arm Registry.

The TEAM-HF Randomized Arm is a prospective, randomized, open-label study of the HeartMate 3 (HM3) left ventricular assist system (LVAS) versus continued GDMT in non-inotrope dependent HF patients. The objectives of the Randomized Arm are 1) To establish an objective disease-state criteria to trigger referral for a HM3 LVAS and 2) Demonstrate improvement in survival when non-inotrope dependent advanced HF patients are treated with the HM3 LVAS compared to being managed on medical therapy alone.

The TEAM-HF Single Arm Registry is a prospective, single-arm, open-label study of non-inotrope dependent HF patients who do not meet a mean PAP threshold after GDMT optimization. The objective of the Single Arm Registry is to characterize the progression of patients with non-inotrope dependent HF without elevated PAP.

Inclusion Criteria:

1. Subject has provided written informed consent by signing the study Informed Consent Form (ICF) prior to any clinical investigation-related procedure
2. LVEF ≤30% and Cardiac Index ≤ 2.5 L/min/m²
3. Limited functional status as demonstrated by 6MWT ≤ 350 m due to HF related reasons OR peak VO2 ≤ 14 mL/kg/min (or <50% of predicted peak VO2 value)
4. NYHA Class IIIB or NYHA Class IV
5. Subject has ≥ 1 Heart Failure Hospitalization in the last 12 months
6. Subject is already implanted with a CardioMEMS PA Sensor OR willing to undergo a CardioMEMS PA Sensor implant
7. Subject is willing and able to be implanted with the HM3 LVAS if randomized to HM3 Group

Randomization Criteria:

1. Subject has been implanted with a CardioMEMS PA Sensor for at least 90 days.
2. Subject is receiving guideline directed medical therapy with optimal doses (or documented medication contraindication or intolerance) of betablockers, Angiotensin-Converting-Enzyme-inhibitors or Angiotensin II Receptor Blockers or angiotensin receptor neprilysin inhibitor (if eligible), Mineralocorticoid Receptor Antagonists, Sodium-Glucose co-Transporter-2 (SGLT2) inhibitors, and diuretics for at least 30 of the last 90 days.
3. mean PAP ≥ 30 mmHg.
4. The subject will not be randomized if they have any other factor that represents inordinate risk for either continued GDMT or LVAD implant.

Single Arm Registry Criteria:

1. Subject has received a CardioMEMS PA Sensor implant following enrollment in the trial.
2. Subject is receiving guideline directed medical therapy with optimal doses (or documented medication contraindication or intolerance) of betablockers, Angiotensin-Converting-Enzyme-inhibitors or Angiotensin II Receptor Blockers or angiotensin receptor neprilysin inhibitor (if eligible), Mineralocorticoid Receptor Antagonists, Sodium-Glucose co-Transporter-2 (SGLT2) inhibitors, and diuretics for at least 30 of the last 90 days.
3. mean PAP <30 mmHg

Exclusion Criteria:

1. Subject is < 18 years of age at the time of informed consent.

2. Dependent on IV inotrope in the last 30 days.

3. Contra-indications to HM3 LVAS or CardioMEMS HF system.

4. Etiology of HF due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis, or restrictive cardiomyopathy.

5. Technical obstacles to LVAD or CardioMEMS implantation which pose an inordinately high surgical risk, in the judgment of the implanter.

6. Existence of ongoing MCS.

7. Presence of mechanical aortic valve that will not be either converted to a bioprosthesis or oversewn at the time of LVAD implant.

8. History of any solid organ transplant.

9. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAS management.

10. Presence of an active, uncontrolled infection.

11. Complex congenital heart disease.

12. Currently Pregnant or capable of becoming Pregnant and Unwilling to Use Contraception with LVAD.

13. History of pulmonary embolism within 30 days prior to enrollment or history of recurrent (>1 episode) pulmonary embolism and/or deep vein thrombosis.

14. Planned VAD or Bi-VAD support prior to enrollment.

15. Presence of any one of the following risk factors for or indications of severe end organ dysfunction or failure:

    1. An INR ≥ 2.0 not due to anticoagulation therapy
    2. An eGFR < 30 mL/min/1.73 m2 and nonresponsive to diuretic therapy or receiving chronic dialysis.
    3. Biopsy proven liver cirrhosis.
    4. Need for chronic renal replacement therapy.
    5. History of severe chronic obstructive pulmonary disease (COPD) defined by Forced Expiratory Volume FEV1 < 30% predicted.
    6. History of cerebrovascular disease with significant (> 80%) uncorrected internal carotid stenosis.
    7. Significant peripheral vascular disease (PVD) accompanied by ischemic rest pain or extremity ulceration.

16. Any condition other than HF that could limit survival to less than 24 months.

17. Participation in any other clinical investigation with an active treatment arm that is likely to confound study results or affect the study outcome.