Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study

NCT05136820 | Active Not Recruiting DMC FDA Device

• 1 other identifier: G210281
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (6)

• 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

• 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.

• 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.

• 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.

• 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.

• 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 Outcomes (8)

• Clinical performance - change from baseline in NYHA Classification

  Baseline through end of study, approximately 5 years

• Clinical performance - change from baseline using KCCQ

  Baseline through end of study, approximately 5 years

• Clinical performance - change from baseline using EQ-5D

  Baseline through end of study, approximately 5 years

• Clinical performance - change from baseline using the 6 Minute Walk Test (MWT)

  Baseline through end of study, approximately 5 years

• Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).

  Baseline through 24 Months

Study Arms (4)

Randomization to 6mm AFR device

ACTIVE COMPARATOR

AFR Device 6mm vs Sham procedure

Device: Atrial Flow Regulator

Randomization to 8mm AFR device

ACTIVE COMPARATOR

AFR device 8mm vs Sham procedure

Device: Atrial Flow Regulator

Randomization to sham procedure

SHAM COMPARATOR

Sham procedure to AFR device (6mm or 8mm)

Device: Sham Comparator

Roll-in Arm

OTHER

Patients in the Roll-in Arm will receive the AFR device

Device: Atrial Flow Regulator

Interventions

Atrial Flow Regulator DEVICE

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

Also known as: AFR

Randomization to 6mm AFR device; Randomization to 8mm AFR device; Roll-in Arm

Sham Comparator DEVICE

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

Randomization to sham procedure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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\*.
• 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
• 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.

You may not qualify if:

• 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:
• regurgitation grade ≥3+ or
• severe stenosis of mitral or tricuspid valves, or
• 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

Sponsors & Collaborators

• Occlutech International AB: lead

Study Sites (2)

Arizona Heart Rhythm Center

Phoenix, Arizona, 85016, United States

Location

North Shore Northwell University Hospital Lenox Hill

New York, New York, 10075, United States

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Megan Coylewright, MD, MPH, FSCAI, FACC

  Erlanger Health System

  PRINCIPAL INVESTIGATOR

• Muthiah Vaduganathan, MD, MPH

  Brigham and Women's Hospital Heart and Vascular Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Interventional cardiologist will be unblinded and the Heart failure cardiologist and participants will be blinded. There will also be an unblinded study coordinator and a blinded study coordinator.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 11, 2021
• First Posted: November 29, 2021
• Study Start: March 9, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2029
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)