Clinical trial NCT06526195: Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure
Official title: Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Heart Diseases
Cardiovascular Diseases
Pulmonary Hypertension
Keywords: Heart Failure
Left Ventricular Assist Device (LVAD)
Guideline Directed Medical Therapy (GDMT)
Non-inotrope Dependent
Pulmonary Artery Pressure
Hemodynamic Monitoring
Medical Management
CardioMEMS
HeartMate 3 (HM3)
Ambulatory Advanced Heart Failure
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2024-07-29
Enrollment: 850
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: 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.

Detailed description: 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) Demonstrate improvement in survival when non-inotrope dependent advanced HF patients with elevated mean PAP are treated with the HM3 compared to being managed on medical therapy alone; and 2) To establish an objective disease-state criteria to trigger referral for a HM3 LVAS.

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 follow patients with lower mean PAP to evaluate how their HF progresses and if a delayed HM3 implantation would be beneficial for these patients.

Eligibility criteria: 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 \< 2.2 L/min/m².
3. Limited functional status as demonstrated by 6MWT \< 300 m due to HF related reasons.
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 patient 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. mean PAP \<30 mmHg

Exclusion Criteria:

1. Subject is \< 18 years of age at the time of informed consent.
2. Any use of inotrope therapy 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, severe valvular heart disease, 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 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.

Primary outcomes:
measure: Survival at 2 years free of disabling stroke, reoperation to replace the device, or worsening HF requiring listing for urgent heart transplantation or mechanical circulatory support, enrollment into hospice, or dependence on IV inotropes
timeFrame: 2 years
Secondary outcomes:
measure: Freedom from major adverse events (MAE) in the HM3 group
timeFrame: 1 year
measure: Survival at 2 years
timeFrame: 2 years
measure: Quality of life score assessed with the Kansas City Cardiomyopathy Questionnaire
timeFrame: 2 years
measure: Six-minute walk distance
timeFrame: 2 years
measure: Hospitalizations for HF and/or Urgent HF Visit
timeFrame: 2 years
measure: Days alive and outside of the hospital
timeFrame: 2 years
measure: All-cause hospitalizations
timeFrame: 2 years
Other outcomes:
measure: Finkelstein-Schoenfeld Win Ratio
timeFrame: 5 years
measure: Survival free of urgent LVAD or transplant
timeFrame: 5 years
Locations:
city: Little Rock
country: United States
facility: Baptist Health Medical Center
state: Arkansas
city: Sacramento
country: United States
facility: Sutter Medical Center
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Indianapolis
country: United States
facility: St. Vincent Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Butterworth Hospital
state: Michigan
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: New York-Presbyterian/Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health Midlands
state: South Carolina
city: Memphis
country: United States
facility: The Stern Cardiovascular Foundation
state: Tennessee
city: Austin
country: United States
facility: Ascension Texas Cardiovascular
state: Texas
city: Dallas
country: United States
facility: Baylor University Hospital
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Saxon
city: Berlin
country: Germany
facility: Deutsches Herzzentrum der Charité
city: Riyadh
country: Saudi Arabia
facility: King Fahad Medical City
Study officials:
affiliation: Abbott
name: Kelly O'Connell, PhD
role: STUDY_DIRECTOR
References: