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

Not Applicable

Recruiting

• Conditions: Heart Diseases; Pulmonary Hypertension; Heart Failure; Cardiovascular Diseases
• Interventions: Device: CardioMEMS HF System; Device: HeartMate 3 Left Ventricular Assist System; Other: Guideline Medical Directed Therapy

• Registration Number: NCT06526195
• Lead Sponsor: Abbott Medical Devices

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.

Study Timeline

• Study First Submitted: 2024-07-24
• Study First Submitted QC: 2024-07-24
• Study First Posted: 2024-07-29
• Study Start: 2024-12-13
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-22
• Primary Completion: 2029-09
• Study Completion: 2032-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 850

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Randomized Arm - HM3 Group	CardioMEMS HF System	Patients with elevated mean PAP (mean PAP ≥ 30 mmHg) and randomized to the HM3 group will receive the device within 14 days of randomization.
Single Arm Registry	CardioMEMS HF System	Patients who do not meet the mean PAP threshold (mean PAP \<30 mmHg) and are enrolled in the single arm will continue their medical therapy per established heart failure guidelines.
Randomized Arm - HM3 Group	Guideline Medical Directed Therapy	Patients with elevated mean PAP (mean PAP ≥ 30 mmHg) and randomized to the HM3 group will receive the device within 14 days of randomization.
Single Arm Registry	Guideline Medical Directed Therapy	Patients who do not meet the mean PAP threshold (mean PAP \<30 mmHg) and are enrolled in the single arm will continue their medical therapy per established heart failure guidelines.
Randomized Arm - HM3 Group	HeartMate 3 Left Ventricular Assist System	Patients with elevated mean PAP (mean PAP ≥ 30 mmHg) and randomized to the HM3 group will receive the device within 14 days of randomization.
Randomized Arm - Control Group	Guideline Medical Directed Therapy	Patients with elevated mean PAP (mean PAP ≥ 30 mmHg) and randomized to the control group will continue their medical therapy per established heart failure guidelines.
Randomized Arm - Control Group	CardioMEMS HF System	Patients with elevated mean PAP (mean PAP ≥ 30 mmHg) and randomized to the control group will continue their medical therapy per established heart failure guidelines.

Primary Outcome Measures

Name	Time	Method
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	2 years	The powered primary endpoint will be analyzed at 2 years following the Com-Nougue method and will be compared between the HM3 Group (HM3 LVAD) and the Control Group (GDMT) within the Randomized population.; Primary Endpoint definitions: * Disabling stroke: Modified Rankin Score ≥ 2 at 60 days post-stroke with an increase of at least 1 point compared to the pre-stroke baseline.; * Urgent heart transplantation: United Network for Organ Sharing (UNOS) listing status 1-3 or equivalent; * Enrollment into hospice: admission requiring palliative care for cardiovascular reasons.; * Temporary mechanical circulatory support: short-term univentricular or biventricular support, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), Impella, Percutaneous VAD, etc.; * Dependence on intravenous inotropes: patients are considered inotrope-dependent when attempts to wean result in deteriorating hemodynamics, exacerbation of HF symptoms, or progressive organ dysfunction.

Secondary Outcome Measures

Name	Time	Method
Freedom from major adverse events (MAE) in the HM3 group	1 year	The powered secondary endpoint of freedom from MAE at 1-year will be evaluated in the As-Treated HM3 group against a pre-specified performance goal.; Components of MAE consist of the following: * Disabling stroke (Modified Rankin Score ≥ 2 at 60 days post-stroke with an increase of at least 1 point compared to the pre-stroke baseline); * Non-surgical bleeding (\>14 days post implant) requiring hospitalization; * Driveline infection requiring hospitalization
Survival at 2 years	2 years	The powered secondary endpoint of survival at 2-years will be compared between the HM3 Group and the Control Group within the Randomized population.
Quality of life score assessed with the Kansas City Cardiomyopathy Questionnaire	2 years	The secondary endpoint of Quality of life score at 2-years will be compared between the HM3 Group and the Control Group within the Randomized population. Additionally, the secondary endpoint of Quality of life at 2-years will be descriptively compared between the Single Arm Registry and both the HM3 Group and Control Group of the Randomized Arm separately.; The KCCQ scores are represented on a 0-to-100-point scale, where lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life. Improvement of KCCQ by at least 10 points is considered clinically significant.
Six-minute walk distance	2 years	The secondary endpoint of six-minute walk distance at 2-years will be compared between the HM3 Group and the Control Group within the Randomized population. Additionally, the secondary endpoint of six-minute walk distance at 2-years will be descriptively compared between the Single Arm Registry and both the HM3 Group and Control Group of the Randomized Arm separately.
Hospitalizations for HF and/or Urgent HF Visit	2 years	The secondary endpoint of Hospitalizations for HF and/or Urgent HF Visit at 2-years will be compared between the HM3 Group and the Control Group within the Randomized population. Additionally, the secondary endpoint of Hospitalizations for HF and/or Urgent HF Visit at 2-years will be descriptively compared between the Single Arm Registry and both the HM3 Group and Control Group of the Randomized Arm separately.
Days alive and outside of the hospital	2 years	The secondary endpoint of days alive and outside of the hospital at 2-years will be compared between the HM3 Group and the Control Group within the Randomized population. Additionally, the secondary endpoint of days alive and outside of the hospital at 2-years will be descriptively compared between the Single Arm Registry and both the HM3 Group and Control Group of the Randomized Arm separately.
All-cause hospitalizations	2 years	The secondary endpoint of all-cause hospitalizations at 2-years will be compared between the HM3 Group and the Control Group within the Randomized population. Additionally, the secondary endpoint of all-cause hospitalizations at 2-years will be descriptively compared between the Single Arm Registry and both the HM3 Group and Control Group of the Randomized Arm separately.

Trial Locations

Locations (26)

Baptist Health Medical Center; 🇺🇸 Little Rock, Arkansas, United States

Sutter Medical Center; 🇺🇸 Sacramento, California, United States

Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

St. Vincent Hospital; 🇺🇸 Indianapolis, Indiana, United States

Kansas University Medical Center; 🇺🇸 Kansas City, Kansas, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Spectrum Health Butterworth Hospital; 🇺🇸 Grand Rapids, Michigan, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

North Shore University Hospital; 🇺🇸 Manhasset, New York, United States

New York-Presbyterian/Columbia University Medical Center; 🇺🇸 New York, New York, United States

Carolinas Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Prisma Health Midlands; 🇺🇸 Columbia, South Carolina, United States

The Stern Cardiovascular Foundation; 🇺🇸 Memphis, Tennessee, United States

Ascension Texas Cardiovascular; 🇺🇸 Austin, Texas, United States

Baylor University Hospital; 🇺🇸 Dallas, Texas, United States

The Heart Hospital Baylor Plano; 🇺🇸 Plano, Texas, United States

Scott & White Memorial Hospital; 🇺🇸 Temple, Texas, United States

University of Utah Hospital; 🇺🇸 Salt Lake City, Utah, United States

Deutsches Herzzentrum der Charité; 🇩🇪 Berlin, Germany

King Fahad Medical City; 🇸🇦 Riyadh, Saudi Arabia