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

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

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)

Study Overview

• Status: Completed
• Conditions: Heart Failure; Heart Failure Low Output
• Intervention / Treatment: Device: Occlutech AFR device

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Buitenring Sint-Denijs 30
    • Gent, Buitenring Sint-Denijs 30, Belgium, 9000
      • AZ Maria Middelares
  • Herestraat 49
    • Leuven, Herestraat 49, Belgium, 3000
      • UZ Leuven
  • Laarbeeklaan 101
    • Brussels, Laarbeeklaan 101, Belgium, 1090
      • University Hospital Brussels
  • Merestraat 80
    • Aalst, Merestraat 80, Belgium, 9300
      • Algemeen Stedelijk Ziekenhuis (Asz)
  • Moorselbaan 164
    • Aalst, Moorselbaan 164, Belgium, 9300
      • OLV (Onze-Lieve-Vrouwziekenhuis) Hospital Aalst
• Germany
  • Berlin, Germany
    • Charite - Universitatsmedizin Berlin
  • Berlin, Germany
    • Vivantes Klinikum im Friedrichshain
  • Cologne, Germany
    • Herzzentrum Uniklinik Köln
  • Frankfurt, Germany
    • CardioVasculäres Centrum Frankfurt
  • Hamburg, Germany
    • Cardiologicum Hamburg
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Homburg, Germany
    • University of Homburg
  • Leipzig, Germany
    • Herzzentrum Leipzig
  • Magdeburg, Germany
    • Uniklinikum Magdeburg A. ö. R.
  • Rostock, Germany
    • Universitätsmedizin Rostock
  • Würzburg, Germany
    • University of Würzburg
• Turkey
  • Istanbul, Turkey
    • Bezmialem University
  • Kocaeli, Turkey
    • Kocaeli Universitesi Hastanesi
  • Altındağ
    • Ankara, Altındağ, Turkey, 06110
      • Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi
    • Ankara, Altındağ, Turkey, 06230
      • Hacettepe Üni Hastanesi
  • Bornova
    • İzmir, Bornova, Turkey
      • Ege Universitesi Hastanesi
  • Fatih
    • Istanbul, Fatih, Turkey, 34452
      • Istanbul Universitesi
  • Kartal
    • Istanbul, Kartal, Turkey, 34865
      • Kartal Koşuyolu Yüksek İhtisas Eğitim ve Araştırma Hastanesi
  • Konak
    • İzmir, Konak, Turkey, 35020
      • Tepecik Eğitim Ve Araştırma Hastanesi
  • Merkez
    • Sivas, Merkez, Turkey, 58140
      • Sivas Cumhuriyet Üniversitesi Tıp Fakültesi Araştırma ve Uygulama Hastanesi
  • Çiğli
    • İzmir, Çiğli, Turkey, 35620
      • İzmir Katip Çelebi Üniversitesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria. Each patient must fulfill ALL of the following criteria and details:

1. Age ≥18 years
2. Heart failure resulting in NYHA class III or IV ambulatory
3. Ongoing management of heart failure according to ESC (European Society of Cardiology) (15) -guidelines during previous ≥6 months
4. Control with Arrhythmia with heart rate <110bpm
5. Life expectancy of at least 1 year
6. The patient should have the ability to fluently speak and understand the language in which the study is being conducted
7. Written, informed consent by the patient for participation in the study and agreement to comply with the follow-up schedule
8. Patient has had a successful Balloon Atrial Septostomy (BAS) procedure and is in a stable hemodynamic state, as assessed by the investigator
9. 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
10. 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
11. Transseptal catheterization and femoral vein access is determined to be feasible

Exclusion Criteria:

1. Local or generalized sepsis or other acute infection(s)
2. Any coagulation disorder, if clinically relevant in the opinion of the operator.
3. Allergy to nickel and/or titanium and/or nickel/titanium-based materials, if not medically manageable
4. Allergy to anti-platelet, -coagulant, or -thrombotic therapy, if not medically manageable
5. Intolerance to contrast agents, if not medically manageable
6. Participation in another medical trial testing a therapy less than 30 days before the intended AFR implantation procedure
7. Trans-oesophageal echocardiography and / or use of general anaesthetic is contraindicated
8. Breast feeding women

9. Pregnancy

   Processes which would technically disturb the safe intervention as planned:

10. Occluded inferior vena cava access
11. History of ASD and/or atrial septal repair or closure device in place

12. Intracardiac thrombus

    Clinical conditions:

13. 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]
14. Patients who has unstable and intractable angina pectoris

15. Evidence of right heart failure defined as (by ECHO)

    1. Severe Right Ventricular Dysfunction (TAPSE < 14 mm)
    2. Severe Right Ventricular Dilatation (RV volume ≥ LV volume)
    3. Severe pulmonary hypertension (PASP > 60 mm Hg)
16. Active malignancy
17. Severe valve disease, or implanted mechanical valve prosthesis
18. Congenital heart defect
19. Large PFO with significant atrial septal aneurysm (bubble test shows more than 20 bubbles)
20. Inability to perform 6-minutes walking test
21. Clinically relevant thrombocytopenia, thrombocytosis, leukopenia, or anemia
22. Symptomatic carotid artery disease
23. Mitral valve stenosis
24. 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
25. Systolic blood pressure of >170 mmHg, despite medical therapy
26. Severe lung disease (causing PHT with systolic PAP >60mmHg)
27. Pulmonary Hypertension (Systolic PAP >60mmHg)
28. TIA or stroke within the last 6 months
29. Scheduled for heart transplantation
30. Bleeding disorders (INR > 2.0, Thrombocytes < 100.000, Hemoglobin <8.0 gr/dl)
31. Myocardial infarction or percutaneous intervention or CABG (all within the last 3 month) or indication for a coronary intervention
32. Resyncronization therapy started within the last 6 months
33. Aneurysm of the septum
34. Hypertrophied Inter Atrial Septum (IAS) > 10mm depth
35. Hypertrophic Obstructive Cardiomyopathy (HOCM) or infiltrative CM as cause of HF
36. Thromboembolic events within the last 6 months
37. Dialysis and renal insufficiency requiring dialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Occlutech AFR Device; 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; Catheter-guided placement of an AFR device following balloon atrial septostomy.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Occlutech International AB

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2017
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): March 2, 2022

Study Registration Dates

• First Submitted: January 17, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 24, 2017

Study Record Updates

• Last Update Posted (Actual): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Occ2016_06

Plan for Individual participant data (IPD)

Study Data/Documents

1. Publications
   Information identifier: NCT03030274
   Information comments: Christina Paitazoglou 1, Ramazan Özdemir, Roman Pfister, Martin W Bergmann, Jozef Bartunek, Teoman Kilic, Alexander Lauten, Alexander Schmeisser, Mehdi Zoghi, Stefan Anker, Horst Sievert, Felix Mahfoud_The AFR-PRELIEVE trial: a prospective, non-randomised, pilot study to assess the Atrial Flow Regulator (AFR) in heart failure patients with either preserved or reduced ejection fraction
2. Publications
   Information identifier: NCT03030274
   Information comments: Christina Paitazoglou 1, Martin W Bergmann 1, Ramazan Özdemir 2, Roman Pfister 3, Jozef Bartunek 4, Teoman Kilic 5, Alexander Lauten 6, Alexander Schmeisser 7, Mehdi Zoghi 8, Stefan D Anker 6, Horst Sievert 9, Felix Mahfoud 10, AFR-PRELIEVE Investigators_One-year results of the first-in-man study investigating the Atrial Flow Regulator for left atrial shunting in symptomatic heart failure patients: the PRELIEVE study
3. Publiactions
   Information identifier: NCT03030274
   Information comments: Nijad Bakhshaliyev 1, Ramazan Ozdemir 1_The impact of atrial flow regulator implantation on hemodynamic parameters in patients with heart failure

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No