Clinical trial NCT05136820: Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study
Official title: Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
Heart Failure With Reduced Ejection Fraction (HFrEF)
Keywords: Heart Failure
Preserved Ejection Fraction
Reduced Ejection Fraction
HFpEF
HFrEF
Lead sponsor: Occlutech International AB
Sponsor class: INDUSTRY
First posted: 2021-11-29
Enrollment: 698
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients will be identified from the investigator's pool of heart failure patients who are symptomatic on stable guideline directed medical therapy. An electronic randomization scheme in the EDC system will be used to minimize risk of bias in the investigation
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months
timeFrame: Baseline through 12 months
measure: Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality
timeFrame: 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.
measure: Composite Primary Efficacy Endpoint - Frequency of heart transplant or Left Ventricular Assist Device (LVAD)
timeFrame: 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.
measure: Composite Primary Efficacy Endpoint - Total rate of Heart Failure Hospitalizations
timeFrame: 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.
measure: Composite Primary Efficacy Endpoint - Total rate of Heart Failure Treatment Intensification
timeFrame: 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.
measure: Composite Primary Efficacy Endpoint - KCCQ Score
timeFrame: Baseline through 6 months. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.
Secondary outcomes:
measure: Clinical performance - change from baseline in NYHA Classification
timeFrame: Baseline through end of study, approximately 5 years
measure: Clinical performance - change from baseline using KCCQ
timeFrame: Baseline through end of study, approximately 5 years
measure: Clinical performance - change from baseline using EQ-5D
timeFrame: Baseline through end of study, approximately 5 years
measure: Clinical performance - change from baseline using the 6 Minute Walk Test (MWT)
timeFrame: Baseline through end of study, approximately 5 years
measure: Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).
timeFrame: Baseline through 24 Months
measure: Components of Device Performance- Device placed in-situ as assessed by Investigator
timeFrame: Implant through end of study, approximately 5 years
measure: Components of Device Performance - Patency: Evidence of left to right shunt through AFR device
timeFrame: Implant through end of study, approximately 5 years
measure: Components of Device Performance- Implant embolization and clinically significant device migration
timeFrame: Implant through end of study, approximately 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ascension St. Vincent's
state: Alabama
city: Phoenix
country: United States
facility: Arizona Heart Rhythm Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Long Beach
country: United States
facility: Memorial Heart Institute Long Beach
state: California
city: Colorado Springs
country: United States
facility: University of Colorado Health Memorial Hospital
state: Colorado
city: Lakewood
country: United States
facility: Colorado Heart & Vascular
state: Colorado
city: Newark
country: United States
facility: ChristianaCare Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Baptist Health Research Institute
state: Florida
city: Dahlonega
country: United States
facility: Northside Hospital Cardiovascular Institute
state: Georgia
city: Coeur d'Alene
country: United States
facility: Kootenai Health
state: Idaho
city: Indianapolis
country: United States
facility: Community Health Network, Inc
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Duluth
country: United States
facility: Essentia Health
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Edison
country: United States
facility: Hackensack Meridian Health JFK University Medical Center
state: New Jersey
city: New York
country: United States
facility: North Shore Northwell University Hospital Lenox Hill
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Medicine
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Columbia
country: United States
facility: Prisma Health
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Institute for Clinical Research
state: Tennessee
city: Houston
country: United States
facility: The University Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: Erlanger Health System
name: Megan Coylewright, MD, MPH, FSCAI, FACC
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital Heart and Vascular Center
name: Muthiah Vaduganathan, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: