Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study
- Conditions
- Heart Failure With Preserved Ejection Fraction (HFpEF)Heart Failure With Reduced Ejection Fraction (HFrEF)
- Interventions
- Device: Atrial Flow RegulatorDevice: Sham Comparator
- Registration Number
- NCT05136820
- Lead Sponsor
- Occlutech International AB
- Brief Summary
The purpose of this clinical study is to assess the safety and effectiveness of the Atrial Flow Regulator in the treatment of subjects, 18 years of age or older, who have symptomatic heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) while on stable guideline directed medical therapy (GDMT) as outlined in the Guidelines for the Management of Heart Failure.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 698
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Aged ≥18 years
-
Presence of chronic symptomatic HF (NYHA ≥class 2) and at least one of the following:
-
Previous heart failure hospitalization within 6 months of informed consent or
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Elevated NT-proBNP (or BNP):
- If in Sinus Rhythm, must have a corrected elevated Brain Natriuretic Peptide (BNP) level of at least 300 pg/mL or an N-terminal pro-BNP (NT-proBNP) level of at least 900 pg/mL, according to local measurement, within 2 months of the Screening Visit during a clinically stable period*.
- If in Atrial Fibrillation or Atrial Flutter, must have a corrected elevated BNP level of at least 400 pg/mL or an NT-proBNP level of at least 1200 pg/mL within 2 months of the Screening Visit during a clinically stable period*.
-
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If LVEF documented at screening is >55%, then must have one of either:
- Left atrial enlargement (LA diameter >2.3 cm/m2 or LA volume index >28 mL/m2), or
- PCWP ≥ 15 mmHg at rest within previous 12 months, or
- LVEDP ≥15 mmHg at rest within previous 12 months
-
6 MWT distance 100-450 meters
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Treated with maximally tolerated doses of class I GDMT and class electrical therapies (CRT and ICD) according to latest applicable guidelines (e.g., AHA or ESC) for at least 2 months prior to informed consent, and a stable dose diuretic for at least 1 month prior to informed consent.
General
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Myocardial infarction and/or revascularization with percutaneous intervention (PCI) or coronary artery bypass grafting (CABG) within 3 months prior to informed consent
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Surgical or transcatheter valve (aortic, mitral, or tricuspid) repair or replacement within 2 months prior to informed consent
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Automated implantable cardioverter defibrillator (AICD) placement within 2 months prior to informed consent
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Resynchronization therapy started within 3 months prior to informed consent
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Major surgery within 3 months prior to informed consent
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History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within 6 months prior to informed consent, or any prior stroke with persistent neurologic deficit, or any prior intracranial bleed, or known intracerebral aneurysm, AV malformation or other intracranial pathology increasing the risk of bleeding
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Uncontrolled atrial fibrillation with resting heart rate >110 beats per minute despite medical therapy
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Documented history of non-dilated cardiomyopathy (obstructive hypertrophic, restrictive, infiltrative) or pericardial disease
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Clinically significant valvular heart disease:
- regurgitation grade ≥3+ or
- severe stenosis of mitral or tricuspid valves, or
- moderate or greater stenosis of aortic valves
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Prior diagnosis of pulmonary hypertension with current treatment with one or more pulmonary hypertension specific drugs (e.g. endothelin receptor antagonists (ERAs), phosphodiesterase inhibitors (PDE 5 Inhibitors) or prostacyclin analogues)
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Uncontrolled hypertension, Systolic Blood Pressure (SBP) ≥160 or Diastolic Blood Pressure (DBP) ≥100 mmHg despite medical therapy at the time of screening visit
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Previous interventional or surgical atrial septal defect (ASD) or patent foramen ovale (PFO) closure
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Inadequate vascular access for implantation of shunt, e.g., suboptimal femoral venous access for transseptal catheterization or inferior vena cava (IVC) is not patent
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Chronic kidney disease currently requiring dialysis
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Allergy or contraindication to aspirin, or clopidogrel and prasugrel and ticagrelor, or heparin and bivalirudin
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Bleeding disorders (international normalized ratio [INR] >2.0, platelet count <100,000 x 109/L, hemoglobin <10.0 g/dL)
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Known clinically significant untreated carotid artery stenosis likely to require intervention, at discretion of investigator
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Current untreated coronary artery disease with indication for revascularization
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Significant Right Ventricular dysfunction demonstrated by:
- Tricuspid Annular Plane Systolic Excursion (TAPSE) <16mm or
- Right Ventricular Fractional Area Change (RVFAC) ≤30%
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Right Atrial Volume Index (RAVI) > 31ml/m2
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Left Ventricular End-Diastolic Diameter (LVEDD) > 8.0 cm as assessed by echocardiography
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Severe COPD requiring oral steroid therapy or daytime oxygen
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Echocardiographic evidence of intra-cardiac mass, thrombus, or vegetation
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On current immunosuppression or systemic oral steroid treatment
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Any condition that limits exercise tolerance other than heart failure (e.g., peripheral vascular disease, orthopedic issues, angina, other), at the discretion of the Investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Roll-in Arm Atrial Flow Regulator Patients in the Roll-in Arm will receive the AFR device Randomization to sham procedure Sham Comparator Sham procedure to AFR device (6mm or 8mm) Randomization to 8mm AFR device Atrial Flow Regulator AFR device 8mm vs Sham procedure Randomization to 6mm AFR device Atrial Flow Regulator AFR Device 6mm vs Sham procedure
- Primary Outcome Measures
Name Time Method Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months Baseline through 12 months The Primary Safety Endpoint is defined as Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months of randomization. MACNE includes all-cause mortality, stroke, systemic thromboembolism, open cardiac surgery or major endovascular repair, and major bleeding (BARC 3-5).
Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. Incidence of and time to cardiovascular mortality through 12-24 months
Composite Primary Efficacy Endpoint - Total rate of Heart Failure Treatment Intensification Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. Total rate (first plus recurrent) per patient year of heart failure treatment intensification event and time-to-first heart failure treatment intensification event through 12-24 months
Composite Primary Efficacy Endpoint - Frequency of heart transplant or Left Ventricular Assist Device (LVAD) Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. Incidence of and time to heart transplant or LVAD
Composite Primary Efficacy Endpoint - Total rate of Heart Failure Hospitalizations Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. Total rate (first plus recurrent) per patient year of heart failure hospitalization admissions and time to first heart failure hospitalizations through 12-24 months
Composite Primary Efficacy Endpoint - KCCQ Score Baseline through 6 months. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. Change in baseline KCCQ total summary score at 6-months
- Secondary Outcome Measures
Name Time Method Clinical performance - change from baseline using EQ-5D Baseline through end of study, approximately 5 years Clinical performance assessed by the change from baseline using EQ-5D
Components of Device Performance - Patency: Evidence of left to right shunt through AFR device Implant through end of study, approximately 5 years Analysis on components of device performance- Patency: Evidence of left to right shunt through AFR device as assessed by core lab
Clinical performance - change from baseline using KCCQ Baseline through end of study, approximately 5 years Clinical performance assessed by the change from baseline using KCCQ
Clinical performance - change from baseline using the 6 Minute Walk Test (MWT) Baseline through end of study, approximately 5 years Clinical performance assessed by the change from baseline using the 6 Minute Walk Test (MWT)
Clinical performance - change from baseline in NYHA Classification Baseline through end of study, approximately 5 years Clinical performance assessed by the change from baseline in NYHA Classification
Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement). Baseline through 24 Months Analysis on components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).
Components of Device Performance- Device placed in-situ as assessed by Investigator Implant through end of study, approximately 5 years Analysis on components of device performance (Device placed in-situ as assessed by Investigator)
Components of Device Performance- Implant embolization and clinically significant device migration Implant through end of study, approximately 5 years Analysis on components of device performance- Implant embolization and clinically significant device migration (i.e. SAEs probably related to device).
Trial Locations
- Locations (25)
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Stony Brook Medicine
🇺🇸Stony Brook, New York, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Arizona Heart Rhythm Center
🇺🇸Phoenix, Arizona, United States
Oklahoma Heart Hospital
🇺🇸Oklahoma City, Oklahoma, United States
Prisma Health
🇺🇸Columbia, South Carolina, United States
Ascension St. Vincent's
🇺🇸Birmingham, Alabama, United States
University of Colorado Health Memorial Hospital
🇺🇸Colorado Springs, Colorado, United States
Memorial Heart Institute Long Beach
🇺🇸Long Beach, California, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
ChristianaCare Christiana Hospital
🇺🇸Newark, Delaware, United States
Colorado Heart & Vascular
🇺🇸Lakewood, Colorado, United States
Baptist Health Research Institute
🇺🇸Jacksonville, Florida, United States
Community Health Network, Inc
🇺🇸Indianapolis, Indiana, United States
Essentia Health
🇺🇸Duluth, Minnesota, United States
Northside Hospital Cardiovascular Institute
🇺🇸Dahlonega, Georgia, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
North Shore Northwell University Hospital Lenox Hill
🇺🇸New York, New York, United States
Hackensack Meridian Health JFK University Medical Center
🇺🇸Edison, New Jersey, United States
Erlanger Institute for Clinical Research
🇺🇸Chattanooga, Tennessee, United States
The University Health Science Center at Houston
🇺🇸Houston, Texas, United States
Kootenai Health
🇺🇸Coeur d'Alene, Idaho, United States
University of Arizona College of Medicine
🇺🇸Tucson, Arizona, United States