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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05136820
Other study ID # G210281
Secondary ID
Status Active, not recruiting
Phase N/A
First received
Last updated
Start date March 9, 2023
Est. completion date February 2029

Study information

Verified date October 2023
Source Occlutech International AB
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 698
Est. completion date February 2029
Est. primary completion date February 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility General Inclusion Criteria: - Aged =18 years - Presence of chronic symptomatic HF (NYHA =class 2) and at least one of the following: 1. Previous heart failure hospitalization within 6 months of informed consent or 2. Elevated NT-proBNP (or BNP): 1. 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*. 2. 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*. - If LVEF documented at screening is >55%, then must have one of either: 1. Left atrial enlargement (LA diameter >2.3 cm/m2 or LA volume index >28 mL/m2), or 2. PCWP = 15 mmHg at rest within previous 12 months, or 3. LVEDP =15 mmHg at rest within previous 12 months - 6 MWT distance 100-450 meters - 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 Exclusion Criteria: - Myocardial infarction and/or revascularization with percutaneous intervention (PCI) or coronary artery bypass grafting (CABG) within 3 months prior to informed consent - Surgical or transcatheter valve (aortic, mitral, or tricuspid) repair or replacement within 2 months prior to informed consent - Automated implantable cardioverter defibrillator (AICD) placement within 2 months prior to informed consent - Resynchronization therapy started within 3 months prior to informed consent - Major surgery within 3 months prior to informed consent - 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 - Uncontrolled atrial fibrillation with resting heart rate >110 beats per minute despite medical therapy - Documented history of non-dilated cardiomyopathy (obstructive hypertrophic, restrictive, infiltrative) or pericardial disease - Clinically significant valvular heart disease: 1. regurgitation grade =3+ or 2. severe stenosis of mitral or tricuspid valves, or 3. moderate or greater stenosis of aortic valves - 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) - Uncontrolled hypertension, Systolic Blood Pressure (SBP) =160 or Diastolic Blood Pressure (DBP) =100 mmHg despite medical therapy at the time of screening visit - Previous interventional or surgical atrial septal defect (ASD) or patent foramen ovale (PFO) closure - Inadequate vascular access for implantation of shunt, e.g., suboptimal femoral venous access for transseptal catheterization or inferior vena cava (IVC) is not patent - Chronic kidney disease currently requiring dialysis - Allergy or contraindication to aspirin, or clopidogrel and prasugrel and ticagrelor, or heparin and bivalirudin - Bleeding disorders (international normalized ratio [INR] >2.0, platelet count <100,000 x 109/L, hemoglobin <10.0 g/dL) - Known clinically significant untreated carotid artery stenosis likely to require intervention, at discretion of investigator - Current untreated coronary artery disease with indication for revascularization - Significant Right Ventricular dysfunction demonstrated by: 1. Tricuspid Annular Plane Systolic Excursion (TAPSE) <16mm or 2. Right Ventricular Fractional Area Change (RVFAC) =30% - Right Atrial Volume Index (RAVI) > 31ml/m2 - Left Ventricular End-Diastolic Diameter (LVEDD) > 8.0 cm as assessed by echocardiography - Severe COPD requiring oral steroid therapy or daytime oxygen - Echocardiographic evidence of intra-cardiac mass, thrombus, or vegetation - On current immunosuppression or systemic oral steroid treatment - 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


Related Conditions & MeSH terms

  • Heart Failure
  • Heart Failure With Preserved Ejection Fraction (HFpEF)
  • Heart Failure With Reduced Ejection Fraction (HFrEF)

Intervention

Device:
Atrial Flow Regulator
Subjects will be randomized 1:1:1 where subjects will either receive the 6mm AFR device, 8mm AFR device or Sham procedure.
Sham Comparator
Subjects will be randomized 1:1:1 where subjects will either receive the 6mm AFR device, 8mm AFR device or Sham procedure.

Locations

Country Name City State
United States Ascension St. Vincent's Birmingham Alabama
United States Erlanger Institute for Clinical Research Chattanooga Tennessee
United States Kootenai Health Coeur d'Alene Idaho
United States University of Colorado Health Memorial Hospital Colorado Springs Colorado
United States Prisma Health Columbia South Carolina
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States Northside Hospital Cardiovascular Institute Dahlonega Georgia
United States Essentia Health Duluth Minnesota
United States Hackensack Meridian Health JFK University Medical Center Edison New Jersey
United States The University Health Science Center at Houston Houston Texas
United States University of Texas Health Science Center at Houston Houston Texas
United States Community Health Network, Inc Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Baptist Health Research Institute Jacksonville Florida
United States Colorado Heart & Vascular Lakewood Colorado
United States Memorial Heart Institute Long Beach Long Beach California
United States University of Louisville Louisville Kentucky
United States North Shore Northwell University Hospital Lenox Hill New York New York
United States ChristianaCare Christiana Hospital Newark Delaware
United States Oklahoma Heart Hospital Oklahoma City Oklahoma
United States Arizona Heart Rhythm Center Phoenix Arizona
United States The University of Texas Health Science Center at San Antonio San Antonio Texas
United States Stony Brook Medicine Stony Brook New York
United States University of Arizona College of Medicine Tucson Arizona
United States MedStar Washington Hospital Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Occlutech International AB

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 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). Baseline through 12 months
Primary Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality Incidence of and time to cardiovascular mortality through 12-24 months 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.
Primary Composite Primary Efficacy Endpoint - Frequency of heart transplant or Left Ventricular Assist Device (LVAD) Incidence of and time to heart transplant or 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.
Primary Composite Primary Efficacy Endpoint - Total rate of Heart Failure Hospitalizations Total rate (first plus recurrent) per patient year of heart failure hospitalization admissions and time to first heart failure hospitalizations through 12-24 months 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.
Primary Composite Primary Efficacy Endpoint - Total rate of Heart Failure Treatment Intensification 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 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.
Primary Composite Primary Efficacy Endpoint - KCCQ Score Change in baseline KCCQ total summary score at 6-months Baseline through 6 months. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.
Secondary Clinical performance - change from baseline in NYHA Classification Clinical performance assessed by the change from baseline in NYHA Classification Baseline through end of study, approximately 5 years
Secondary Clinical performance - change from baseline using KCCQ Clinical performance assessed by the change from baseline using KCCQ Baseline through end of study, approximately 5 years
Secondary Clinical performance - change from baseline using EQ-5D Clinical performance assessed by the change from baseline using EQ-5D Baseline through end of study, approximately 5 years
Secondary Clinical performance - change from baseline using the 6 Minute Walk Test (MWT) Clinical performance assessed by the change from baseline using the 6 Minute Walk Test (MWT) Baseline through end of study, approximately 5 years
Secondary Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement). Analysis on components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement). Baseline through 24 Months
Secondary Components of Device Performance- Device placed in-situ as assessed by Investigator Analysis on components of device performance (Device placed in-situ as assessed by Investigator) Implant through end of study, approximately 5 years
Secondary Components of Device Performance - Patency: Evidence of left to right shunt through AFR device Analysis on components of device performance- Patency: Evidence of left to right shunt through AFR device as assessed by core lab Implant through end of study, approximately 5 years
Secondary Components of Device Performance- Implant embolization and clinically significant device migration Analysis on components of device performance- Implant embolization and clinically significant device migration (i.e. SAEs probably related to device). Implant through end of study, approximately 5 years
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