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.
Brief Title
Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure
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) 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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
925-989-5982
Central Contact Email
nourdine.chakouri@abbott.com
Completion Date
Completion Date Type
Estimated
Conditions
Heart Failure
Heart Diseases
Cardiovascular Diseases
Pulmonary Hypertension
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 ≤ 2.5 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.
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.
Inclusion 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 ≤ 2.5 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
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
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06526195
Org Class
Industry
Org Full Name
Abbott Medical Devices
Org Study Id
ABT- CIP-10521
Overall Status
Recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure
Primary Outcomes
Outcome Description
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 Intention-to-treat (ITT) population.
Outcome 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
Outcome Time Frame
2 years
Secondary Outcomes
Outcome Description
The powered secondary endpoint of Rate of Safety Outcomes at 1-year will be evaluated within the Intention-to-treat (ITT) population against a pre-specified performance goal.
Components consist of the following:
1. Heart failure hospitalization
2. Major Adverse Event (MAE) including:
* Stroke
* Non-surgical bleeding (\>14 days post implant) requiring hospitalization
* Renal failure requiring hospitalization
* Driveline infection requiring hospitalization
Components consist of the following:
1. Heart failure hospitalization
2. Major Adverse Event (MAE) including:
* Stroke
* Non-surgical bleeding (\>14 days post implant) requiring hospitalization
* Renal failure requiring hospitalization
* Driveline infection requiring hospitalization
Outcome Time Frame
1 year
Outcome Measure
Rate of Safety Outcomes at 1-year
Outcome Description
The powered secondary endpoint of survival at 2-years will be compared between the HM3 Group and the Control Group within the Intention-to-treat (ITT) population.
Outcome Time Frame
2 years
Outcome Measure
Survival at 2 years
Outcome Description
The secondary endpoint of Quality-of-life score at 2-years will be compared between the HM3 Group and the Control Group within the Intention-to-treat (ITT) 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.
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.
Outcome Time Frame
2 years
Outcome Measure
Quality of life score assessed with the Kansas City Cardiomyopathy Questionnaire
Outcome Description
The secondary endpoint of six-minute walk distance at 2-years will be compared between the HM3 Group and the Control Group within the Intention-to-treat (ITT) 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.
Outcome Time Frame
2 years
Outcome Measure
Six-minute walk distance
Outcome Description
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 Intention-to-treat (ITT) 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.
Outcome Time Frame
2 years
Outcome Measure
Hospitalizations for HF and/or Urgent HF Visit
Outcome Description
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 Intention-to-treat (ITT) 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.
Outcome Time Frame
2 years
Outcome Measure
Days alive and outside of the hospital
Outcome Description
The secondary endpoint of all-cause hospitalizations at 2-years will be compared between the HM3 Group and the Control Group within the Intention-to-treat (ITT) 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.
Outcome Time Frame
2 years
Outcome Measure
All-cause hospitalizations
Outcome Description
The secondary endpoint of all adverse events (including all strokes) regardless of severity at 2-years will be compared between the HM3 Group and the Control Group within the Intention-to-treat (ITT) population. Additionally, the secondary endpoint of all adverse events (including all strokes) regardless of severity 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.
Outcome Time Frame
2 years
Outcome Measure
All adverse events (including all strokes) regardless of severity
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Yogita Rochlani
Investigator Email
yrochlani@montefiore.org
Investigator Department
Medicine
Investigator Division
Cardiology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Cardiology
Categories Mesh Debug
Heart/Cardiovascular --- HEART FAILURE
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Heart/Cardiovascular --- HYPERTENSION
Blood & Bone Marrow Cancers --- VASCULAR DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
MeSH Terms
HEART FAILURE
HEART DISEASES
CARDIOVASCULAR DISEASES
HYPERTENSION, PULMONARY
LUNG DISEASES
RESPIRATORY TRACT DISEASES
HYPERTENSION
VASCULAR DISEASES