Heart Failure
Conditions
Brief summary
This is a prospective, multi-center, randomized, sham-controlled, double-blinded (participant and outcomes assessor) clinical trial.
Detailed description
The objectives of this trial are to assess the safety, performance, and effectiveness of the Edwards APTURE transcatheter shunt system when used for the treatment of patients with heart failure with preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction (LVEF \>40%) who remain symptomatic despite guideline-directed medical therapy (GDMT)
Interventions
DEVICEEdwards APTURE transcatheter shunt system
Treatment with APTURE shunt
DIAGNOSTIC_TESTSham procedure
CS angiography
Sponsors
Edwards Lifesciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: • Symptomatic heart failure 1. A primary diagnosis of HFmrEF or HFpEF (LVEF \> 40%), and 2. NYHA class II to ambulatory NYHA class IV (IVa), and 3. Documentation of at least one of the following from the date of initial informed consent or date of enrollment: i. Within the prior 12 months, EITHER: * HF hospital admission (with HF as the primary or secondary diagnosis) * Treatment with intravenous (IV) or intensification of oral diuretics for HF ii. Within the prior 6 months, EITHER: * BNP value \> 35 pg/ml in normal sinus rhythm (NSR) or paroxysmal atrial fibrillation (AF) * BNP \> 125 pg/ml for permanent or long-term persistent AF * NT-proBNP \> 125 pg/ml in NSR or paroxysmal AF * NT-proBNP \> 375 pg/ml for permanent or long-term persistent AF d. There is objective evidence of cardiogenic pulmonary congestion based on hemodynamic criteria obtained by right heart catheterization (RHC) at exercise, and confirmed by hemodynamics core lab as: As measured at end-expiration, pulmonary capillary wedge pressure (PCWP) at ≥ 20 Watts exercise (PCWP ≥ 20W) is elevated to ≥ 25 mmHg and exceeds \[the corresponding\] right atrial pressure (RAP) by ≥ 8 mmHg • In the judgment of the treating physician and the Central Screening Committee the patient is on GDMT for HFpEF/HFmrEF for \>30 days prior to screening and baseline assessments, that is expected to be maintained without change for 6 months. Key
Exclusion criteria
* Severe heart failure defined as one or more of the below: 1. ACC/AHA/ESC Stage D HF, non-ambulatory NYHA Class IV HF 2. If Body Mass Index (BMI) \< 30, cardiac index \< 2.0 L/min/m2 3. If BMI ≥ 30, cardiac index \< 1.8 L/min/m2 4. Inotropic infusion (continuous or intermittent) within the past 6 months 5. Patient is on the cardiac transplant waiting list 6. Prior diagnosis of HF with reduced ejection fraction (HFrEF), including patients with improvement in LVEF to \> 40% * Valve disease: 1. Degenerative mitral regurgitation \> moderate 2. Functional or secondary mitral valve regurgitation defined as grade \> moderate 3. Mitral stenosis \> mild 4. Primary or secondary tricuspid valve regurgitation defined as grade \> moderate 5. Aortic valve disease defined as aortic regurgitation grade \> moderate or aortic stenosis \> moderate * More than mild right ventricular (RV) dysfunction as determined by the echo core lab, taking into account the following available parameters: 1. Tricuspid annular plane systolic excursion (TAPSE) \<1.4 cm, or 2. RV size ≥ LV size 3. Right ventricular ejection fraction (RVEF) \< 35%; or 4. Imaging or clinical evidence of congestive hepatopathy * Mean right atrial pressure (mRAP) \> 15 mmHg at rest * Pulmonary vascular resistance (PVR) ≥ 5.0 WU * BMI ≥ 45 * Myocardial infarction (MI) and/or any therapeutic invasive, non-valvular cardiovascular procedure within past 3 months or current indication for coronary revascularization * Stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT) or pulmonary embolus within the past 6 months * Renal insufficiency as determined by creatinine (sCr) level \> 2.5 mg/dL or estimated glomerular filtration rate (eGFR) \< 25ml/min/1.73 m2 by CKD-Epi equation; or currently requiring dialysis * Performance of the six-minute walk test (6MWT) with a distance \< 50m OR \> 450m * Active endocarditis or infection requiring intravenous antibiotics within 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Device + Medical Therapy: Subjects with Early Major Adverse Events | 30 days | Shunt implant safety: proportion of patients in the APTURE shunt group without any serious device or procedure-related (CEC adjudicated) complications (i.e., Major Adverse Cardiovascular, Cerebrovascular, and Renal Events \[MACCRE\]; at 30 days post index procedure or hospital discharge, whichever is later. |
| Mean change in PCWL from baseline at 6 months | 6-months | Hemodynamic Effectiveness: change in pulmonary capillary wedge during load (PCWL, mmHg/W/kg) from baseline at 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KCCQ-OSS change from baseline at 6-month follow-up | 6-months | Change in Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OSS) from baseline at 6-month follow-up. |
| Proportion of individual patient success defined as being free from death, disabling stroke, and HF hospitalization with at least (≥) a 15-point improvement from baseline KCCQ-OSS or at least (≥) a 25m improvement from baseline 6MWT. | 6-months | — |
| 6MWT change from baseline at 6-month follow-up | 6-months | Chang in 6-Minute Walk Test (6MWT) from baseline at 6-month follow-up |
Countries
Brazil, Canada, Germany, Switzerland, United States
Outcome results
None listed