Hemodynamic-GUIDEd Management of Heart Failure

Study Overview
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Brief Summary
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The GUIDE-HF IDE clinical trial is intended to demonstrate the effectiveness of the CardioMEMS™ HF System in an expanded patient population including heart failure (HF) patients outside of the present indication, but at risk for future HF events or mortality.

Detailed Description
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The GUIDE-HF IDE clinical trial is intended to demonstrate the effectiveness of the CardioMEMS™ HF System in an expanded patient population including HF patients outside of the present indication, but at risk for future HF events or mortality. The trial includes patients with New York Heart Association (NYHA) Class II, III, or IV HF who have an elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or an elevated Brain Natriuretic Peptide (BNP)) and/or a prior HF hospitalization (HFH). The GUIDE-HF IDE trial will include approximately 3600 subjects at approximately 140 North American sites and consists of two arms: a Randomized Arm and a Single Arm.

Official Title
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Hemodynamic-GUIDEd Management of Heart Failure

Conditions
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Heart Failure, Heart Failure, Systolic, Heart Failure, Diastolic, Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure NYHA Class IV, Heart Failure，Congestive, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection Fraction, Heart Failure; With Decompensation

Intervention / Treatment
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* Device: CardioMEMS™ HF System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis and treatment for heart failure (HF) (regardless of left ventricular ejection fraction (LVEF)) for > 90 days prior to the date of consent: a. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines as standard-of-care for HF therapy in the United States, with any intolerance documented. GUIDE-HF Randomized Arm Only: NYHA Class II, III or IV HF symptoms documented within 30 days prior to consent. GUIDE-HF Single Arm Only: NYHA Class III HF symptoms documented within 30 days prior to consent. HF hospitalization (HFH) within 12 months prior to consent and/or elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or Brain Natriuretic Peptide (BNP)) within 30 days prior to consent defined as: Subjects with LVEF ≤ 40%: NT-proBNP ≥ 1000 pg/mL (or BNP ≥ 250 pg/mL). Subjects with LVEF > 40%: NT-proBNP ≥ 700 pg/mL (or BNP ≥ 175 pg/mL). Thresholds for NT-proBNP and BNP (for both LVEF ≤ 40% and LVEF > 40%) will be corrected for body mass index (BMI) using a 4% reduction per BMI unit over 25 kg/m2 ≥ 18 years of age Chest circumference of < 65 inches, if BMI is > 35 kg/m2 Written informed consent obtained from subject Willing and able to upload pulmonary artery (PA) pressure information and comply with the follow-up requirements Exclusion Criteria: Intolerance to all neuro-hormonal antagonists (i.e., intolerance to angiotensin converting enzyme-inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin-neprilysin inhibitors (ARNi), hydralazine/isosorbide dinitrate and beta-blockers) ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes) Received or are likely to receive an advanced therapy (e.g., mechanical circulatory support or cardiac transplant) in the next 12 months NYHA Class IV HF patients with: Continuous or chronic use of scheduled intermittent inotropic therapy for HF and an INTERMACS level of ≤ 4, OR Persistence of fluid overload with maximum (or dose equivalent) diuretic intervention Glomerular Filtration Rate (eGFR) < 25 mL/min and non-responsive to diuretic therapy, or receiving chronic dialysis Inability to tolerate or receive dual antiplatelet therapy or anticoagulation therapy for one month post-implantation Significant congenital heart disease that has not been repaired and would prevent implantation of the CardioMEMS™ PA Sensor Implanted with mechanical right heart valve(s) Unrepaired severe valvular disease Pregnant or planning to become pregnant in the next 12 months An active, ongoing infection, defined as being febrile, an elevated white blood cell count, on intravenous antibiotics, and/or positive cultures (blood, sputum or urine). History of current or recurrent (≥ 2 episodes within 5 years prior to consent) pulmonary emboli and/or deep vein thrombosis Major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary intervention, open heart surgery, or stroke, etc.) within 90 days prior to consent Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to consent Enrollment into another trial with an active treatment arm Anticipated life expectancy of < 12 months Any condition that, in the opinion of the Investigator, would not allow for utilization of the CardioMEMS™ HF System to manage the subject using information gained from hemodynamic measurements to adjust medications, including the presence of unexpectedly severe pulmonary hypertension (e.g., trans-pulmonary gradient >15) at implant right heart catheterization (RHC), a history of non-compliance, or any condition that would preclude CardioMEMS™ PA Sensor implantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Arm - Treatment Group<br>Management of subjects based on pulmonary artery (PA) pressure information derived from the CardioMEMS™ HF System. All subjects will receive a CardioMEMS™ HF System. | Device: CardioMEMS™ HF System<br>* The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF.<br>* Other names: CardioMEMS HF System;|
| Experimental: Randomized Arm - Control Group<br>Management of subjects per standard of care (signs, symptoms, weight etc.) without knowledge of PA pressure information derived from the CardioMEMS™ HF System. All subjects will receive a CardioMEMS™ HF System. | Device: CardioMEMS™ HF System<br>* The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF.<br>* Other names: CardioMEMS HF System;|
| Experimental: Single Arm<br>Management of subjects based on PA pressure information derived from the CardioMEMS™ HF System. All subjects will receive a CardioMEMS™ HF System. | Device: CardioMEMS™ HF System<br>* The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF.<br>* Other names: CardioMEMS HF System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Randomized Arm) Composite outcome of (1) HFHs, (2) intravenous diuretic visits, and (3) all-cause mortality | The composite of: The number of recurrent HFHs The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy The number of deaths of any cause added together with equal weighting into a total number of events | 12 months post-implantation | 
| (Single Arm) Composite outcome of (1) HFHs, (2) intravenous diuretic visits, and (3) all-cause mortality | The composite outcome of: The number of recurrent HFHs The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy The number of deaths of any cause added together with equal weighting into a total number of events | 12 months post-implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Randomized Arm) Composite outcome of (1) HFHs and (2) intravenous diuretic visits | The composite outcome of: The number of recurrent HFHs The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events | 12 months post-implantation | 
| (Randomized Arm) EQ-5D-5L | Health status as assessed by the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire | Baseline, 6, and 12 months post-implantation | 
| (Randomized Arm) KCCQ-12 | Health status as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) | Baseline, 6, and 12 months post-implantation | 
| (Randomized Arm) 6MHW Test | Six Minute Hall Walk (6MHW) Test Distance | Baseline, 6, and 12 months post-implantation | 
| (Randomized Arm) HFHs | The number of recurrent HFHs | 12 months post-implantation | 
| (Randomized Arm) Intravenous diuretic visits | The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy | 12 months post-implantation | 
| (Randomized Arm) All-cause mortality | The number of deaths of any cause | 12 months post-implantation | 
| (Randomized Arm) Safety: Freedom from DSRCs | Freedom from device/system related complications (DSRCs) | 12 months post-implantation | 
| (Single Arm) Composite outcome of (1) HFHs and (2) intravenous diuretic visits | The composite outcome of: The number of recurrent HFHs The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events | 12 months post-implantation | 
| (Single Arm) HFHs post- vs. pre-implantation | The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation | 12 months post-implantation | 
| (Single Arm) HFHs | The number of HFHs | 12 months post-implantation | 
| (Single Arm) Intravenous diuretic visits | The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy | 12 months post-implantation | 
| (Single Arm) All-cause mortality | The number of deaths of any cause | 12 months post-implantation | 
| (Single Arm) Safety: Freedom from DSRCs | Freedom from DSRCs | 12 months post-implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Hemodynamic Monitoring, CardioMEMS, Pulmonary Artery Pressure