The Prelieve Trial - Pilot Study to Assess Safety and Efficacy of a Novel Atrial Flow Regulator (AFR) in Heart Failure Patients

Study Overview
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Brief Summary
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This study aims to investigate safety and efficacy of the Occlutech® AFR device in patients with HFrEF (Heart failure with reduced ejection fraction) and HFpEF (Heart failure with preserved ejection fraction)

Detailed Description
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This study will enroll subjects with HFrEF or HFpEF, until a maximum of 100 patients have undergone implantation with the Occlutech® AFR device. Enrolled patients will be stratified according to their ejection fraction as either HFrEF (ejection fraction > 15% and <40 %) or HFpEF ( ejection Fraktion > 40 % to 70 %). It is planned to enroll at least 100 patients per stratification subgroup.

Official Title
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Prospective, Non-randomized, Pilot Study to Assess Safety and Efficacy of a Novel Atrial Flow Regulator (AFR) in Heart Failure Patients With Reduced Ejection Fraction or in Heart Failure Patients With Preserved Ejection Fraction

Conditions
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Heart Failure Low Output, Heart Failure

Intervention / Treatment
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* Device: Occlutech AFR device


Participation Criteria
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Eligibility Criteria
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Inclusion criteria. Each patient must fulfill ALL of the following criteria and details: Age ≥18 years Heart failure resulting in NYHA class III or IV ambulatory Ongoing management of heart failure according to ESC (European Society of Cardiology) (15) -guidelines during previous ≥6 months Control with Arrhythmia with heart rate <110bpm Life expectancy of at least 1 year The patient should have the ability to fluently speak and understand the language in which the study is being conducted Written, informed consent by the patient for participation in the study and agreement to comply with the follow-up schedule Patient has had a successful Balloon Atrial Septostomy (BAS) procedure and is in a stable hemodynamic state, as assessed by the investigator LVEF ≥15% and ≤ 70% , EF measured via Echocardiography 9.1.9.1. And for LVEF ≥ 40% (HFpEF): elevated NT-pro-BNP of ≥ 125 pg/ml Elevated left ventricular filling pressure documented by 10.1. Either Pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure at rest ≥ 15 mmHg and greater then central venous preassure (CVP) 10.2. 10.2. Or: End-expiratory PCWP ≥25 mmHg at exercise and CVP <20 mm Hg Transseptal catheterization and femoral vein access is determined to be feasible Exclusion Criteria: Local or generalized sepsis or other acute infection(s) Any coagulation disorder, if clinically relevant in the opinion of the operator. Allergy to nickel and/or titanium and/or nickel/titanium-based materials, if not medically manageable Allergy to anti-platelet, -coagulant, or -thrombotic therapy, if not medically manageable Intolerance to contrast agents, if not medically manageable Participation in another medical trial testing a therapy less than 30 days before the intended AFR implantation procedure Trans-oesophageal echocardiography and / or use of general anaesthetic is contraindicated Breast feeding women Pregnancy Processes which would technically disturb the safe intervention as planned: Occluded inferior vena cava access History of ASD and/or atrial septal repair or closure device in place Intracardiac thrombus Clinical conditions: Moderate valvular diseases requiring therapy according to current ESC guidelines. Patients are eligible in case therapy is formally indicated but cannot be performed due to technical or medial reasons if the latter is confirmed in writing by the PI in mutual agreement with the heart team and Severe aortic stenosis with valve area < 1.5cm² and Severe AR, TR or MR. Classification of severity of regurgitation should follow the definition provided in Lancelotti et al, Eur Heart J Cardiovasc Imaging 2013 [22] Patients who has unstable and intractable angina pectoris Evidence of right heart failure defined as (by ECHO) Severe Right Ventricular Dysfunction (TAPSE < 14 mm) Severe Right Ventricular Dilatation (RV volume ≥ LV volume) Severe pulmonary hypertension (PASP > 60 mm Hg) Active malignancy Severe valve disease, or implanted mechanical valve prosthesis Congenital heart defect Large PFO with significant atrial septal aneurysm (bubble test shows more than 20 bubbles) Inability to perform 6-minutes walking test Clinically relevant thrombocytopenia, thrombocytosis, leukopenia, or anemia Symptomatic carotid artery disease Mitral valve stenosis Has any condition that, in the opinion of the Investigator, might interfere with the Implantation, might affect the patients well-being thereafter or might interfere with the conduct of the study Systolic blood pressure of >170 mmHg, despite medical therapy Severe lung disease (causing PHT with systolic PAP >60mmHg) Pulmonary Hypertension (Systolic PAP >60mmHg) TIA or stroke within the last 6 months Scheduled for heart transplantation Bleeding disorders (INR > 2.0, Thrombocytes < 100.000, Hemoglobin <8.0 gr/dl) Myocardial infarction or percutaneous intervention or CABG (all within the last 3 month) or indication for a coronary intervention Resyncronization therapy started within the last 6 months Aneurysm of the septum Hypertrophied Inter Atrial Septum (IAS) > 10mm depth Hypertrophic Obstructive Cardiomyopathy (HOCM) or infiltrative CM as cause of HF Thromboembolic events within the last 6 months Dialysis and renal insufficiency requiring dialysis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Occlutech AFR Device<br>Prospective, non-randomized, pilot study to assess safety and efficacy of a novel Atrial Flow Regulator in Heart Failure Patients with with reduced Ejection Fraction (HFrEF) and Heart Failure Patients with preserved Ejection Fraction (HFpEF); the AFR-Prelieve Trial | Device: Occlutech AFR device<br>* Catheter-guided placement of an AFR device following balloon atrial septostomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Device Effects (SADE) within 3 month following implantation. | Incidence of Serious Adverse Device Effects (SADE) following implantation such as: device dislocation / embolization damage to the tricuspid or mitral valve caused by the device intractable arrhythmias caused by the device any circumstances that require device removal. | 0-3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Device Effects (SADE) between 3-12 month following implantation | Incidence of all Serious Adverse Device Effects (SADE) following implantation | 3-12 month | 
| Device placement | Device placement in situ | 0-12 month | 
| Left to Right shunt through the AFR device | Evidence of Left to Right shunt through the AFR device | 0-12 month |