ALT-FLOW II Trial of the Edwards APTURE Transcatheter Shunt System (ALT-FLOW II)

A Randomized, Sham-controlled Clinical Trial for Evaluation of the Edwards APTURE Transcatheter Shunt System (ALT-FLOW II)

This is a prospective, multi-center, randomized, sham-controlled, double-blinded (participant and outcomes assessor) clinical trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: Edwards APTURE transcatheter shunt system; Diagnostic test: Sham procedure

Detailed Description

The objectives of this trial are to assess the safety, performance, and effectiveness of the Edwards APTURE transcatheter shunt system when used for the treatment of patients with heart failure with preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction (LVEF >40%) who remain symptomatic despite guideline-directed medical therapy (GDMT)

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-900
    • Instituto do Coracao da Universidade de Sao Paulo
• Canada
  • Canada
    • Ottawa, Canada, Canada
      • The Ottawa Hospital
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW - Bad Oeynhausen
  • Cologne, Germany, 50937
    • Herzzentrum Universitätsklinikum Köln
  • Dresden, Germany, 01307
    • Herzzentrum Dresden GmbH Universitätsklinik für Innere Medizin und Kardiologie
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg Medizinische Klinik
  • Mainz, Germany, 55131
    • Johannes Gutenberg Universitaet Mainz
• Switzerland
  • Basel, Switzerland, 4031
    • Universitatsspital Basel
• United States
  • California
    • Irvine, California, United States, 92868
      • University of California Irvine
    • La Jolla, California, United States, 92037
      • Scripps Health
    • La Jolla, California, United States, 92027
      • University Of California San Diego
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Illinois
    • Elk Grove, Illinois, United States, 60007
      • Ascension Illinois Heart and Vascular Medical Group
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New York
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital & Heart Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Heart Institute
  • Oregon
    • Oregon City, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425'
      • Medical University of South Carolina Charleston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Symptomatic heart failure

1. A primary diagnosis of HFmrEF or HFpEF (LVEF > 40%), and
2. NYHA class II to ambulatory NYHA class IV (IVa), and
3. Documentation of at least one of the following from the date of initial informed consent or date of enrollment:

i. Within the prior 12 months, EITHER:

• HF hospital admission (with HF as the primary or secondary diagnosis)
• Treatment with intravenous (IV) or intensification of oral diuretics for HF

ii. Within the prior 6 months, EITHER:

• BNP value > 35 pg/ml in normal sinus rhythm (NSR) or paroxysmal atrial fibrillation (AF)
• BNP > 125 pg/ml for permanent or long-term persistent AF
• NT-proBNP > 125 pg/ml in NSR or paroxysmal AF
• NT-proBNP > 375 pg/ml for permanent or long-term persistent AF d. There is objective evidence of cardiogenic pulmonary congestion based on hemodynamic criteria obtained by right heart catheterization (RHC) at exercise, and confirmed by hemodynamics core lab as: As measured at end-expiration, pulmonary capillary wedge pressure (PCWP) at ≥ 20 Watts exercise (PCWP ≥ 20W) is elevated to ≥ 25 mmHg and exceeds [the corresponding] right atrial pressure (RAP) by ≥ 8 mmHg • In the judgment of the treating physician and the Central Screening Committee the patient is on GDMT for HFpEF/HFmrEF for >30 days prior to screening and baseline assessments, that is expected to be maintained without change for 6 months.

Key Exclusion Criteria:

• Severe heart failure defined as one or more of the below:

  1. ACC/AHA/ESC Stage D HF, non-ambulatory NYHA Class IV HF
  2. If Body Mass Index (BMI) < 30, cardiac index < 2.0 L/min/m2
  3. If BMI ≥ 30, cardiac index < 1.8 L/min/m2
  4. Inotropic infusion (continuous or intermittent) within the past 6 months
  5. Patient is on the cardiac transplant waiting list
  6. Prior diagnosis of HF with reduced ejection fraction (HFrEF), including patients with improvement in LVEF to > 40%

• Valve disease:

  1. Degenerative mitral regurgitation > moderate
  2. Functional or secondary mitral valve regurgitation defined as grade > moderate
  3. Mitral stenosis > mild
  4. Primary or secondary tricuspid valve regurgitation defined as grade > moderate
  5. Aortic valve disease defined as aortic regurgitation grade > moderate or aortic stenosis > moderate

• More than mild right ventricular (RV) dysfunction as determined by the echo core lab, taking into account the following available parameters:

  1. Tricuspid annular plane systolic excursion (TAPSE) <1.4 cm, or
  2. RV size ≥ LV size
  3. Right ventricular ejection fraction (RVEF) < 35%; or
  4. Imaging or clinical evidence of congestive hepatopathy
• Mean right atrial pressure (mRAP) > 15 mmHg at rest
• Pulmonary vascular resistance (PVR) ≥ 5.0 WU
• BMI ≥ 45
• Myocardial infarction (MI) and/or any therapeutic invasive, non-valvular cardiovascular procedure within past 3 months or current indication for coronary revascularization
• Stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT) or pulmonary embolus within the past 6 months
• Renal insufficiency as determined by creatinine (sCr) level > 2.5 mg/dL or estimated glomerular filtration rate (eGFR) < 25ml/min/1.73 m2 by CKD-Epi equation; or currently requiring dialysis
• Performance of the six-minute walk test (6MWT) with a distance < 50m OR > 450m
• Active endocarditis or infection requiring intravenous antibiotics within 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APTURE shunt + medical therapy	Device: Edwards APTURE transcatheter shunt system; Treatment with APTURE shunt
Sham Comparator: Sham + medical therapy	Diagnostic test: Sham procedure; CS angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device + Medical Therapy: Subjects with Early Major Adverse Events	Shunt implant safety: proportion of patients in the APTURE shunt group without any serious device or procedure-related (CEC adjudicated) complications (i.e., Major Adverse Cardiovascular, Cerebrovascular, and Renal Events [MACCRE]; at 30 days post index procedure or hospital discharge, whichever is later.	30 days
Mean change in PCWL from baseline at 6 months	Hemodynamic Effectiveness: change in pulmonary capillary wedge during load (PCWL, mmHg/W/kg) from baseline at 6 months.	6-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of individual patient success defined as being free from death, disabling stroke, and HF hospitalization with at least (≥) a 15-point improvement from baseline KCCQ-OSS or at least (≥) a 25m improvement from baseline 6MWT.		6-months
KCCQ-OSS change from baseline at 6-month follow-up	Change in Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OSS) from baseline at 6-month follow-up.	6-months
6MWT change from baseline at 6-month follow-up	Chang in 6-Minute Walk Test (6MWT) from baseline at 6-month follow-up	6-months

Collaborators and Investigators

• Sponsor: Edwards Lifesciences

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): August 31, 2030

Study Registration Dates

• First Submitted: January 6, 2023
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 2022-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No