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

Not Applicable

Recruiting

• Conditions: Heart Failure
• Interventions: Device: Edwards APTURE transcatheter shunt system; Diagnostic Test: Sham procedure

• Registration Number: NCT05686317
• Lead Sponsor: Edwards Lifesciences

Brief Summary

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

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 Timeline

• Study First Submitted: 2023-01-06
• Study First Submitted QC: 2023-01-06
• Study First Posted: 2023-01-17
• Study Start: 2023-04-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-24
• Primary Completion: 2026-01-31
• Study Completion: 2030-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
APTURE shunt + medical therapy	Edwards APTURE transcatheter shunt system	-
Sham + medical therapy	Sham procedure	-

Primary Outcome Measures

Name	Time	Method
Device + Medical Therapy: Subjects with Early Major Adverse Events	30 days	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.
Mean change in PCWL from baseline at 6 months	6-months	Hemodynamic Effectiveness: change in pulmonary capillary wedge during load (PCWL, mmHg/W/kg) from baseline at 6 months.

Secondary Outcome Measures

Name	Time	Method
KCCQ-OSS change from baseline at 6-month follow-up	6-months	Change in Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OSS) from baseline at 6-month follow-up.
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
6MWT change from baseline at 6-month follow-up	6-months	Chang in 6-Minute Walk Test (6MWT) from baseline at 6-month follow-up

Trial Locations

Locations (30)

Medical Center of the Rockies; 🇺🇸 Loveland, Colorado, United States

Ascension Illinois Heart and Vascular Medical Group; 🇺🇸 Elk Grove, Illinois, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Herzzentrum Universitätsklinikum Köln; 🇩🇪 Cologne, Germany

University of California Irvine; 🇺🇸 Irvine, California, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Scripps Health; 🇺🇸 La Jolla, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Northwestern University; 🇺🇸 Evanston, Illinois, United States

Kansas University Medical Center; 🇺🇸 Kansas City, Kansas, United States

Abbott Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

University of Buffalo; 🇺🇸 Buffalo, New York, United States

St. Francis Hospital & Heart Center; 🇺🇸 Roslyn, New York, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Oklahoma Heart Institute; 🇺🇸 Tulsa, Oklahoma, United States

Oregon Health and Science University; 🇺🇸 Oregon City, Oregon, United States

Lankenau Medical Center; 🇺🇸 Wynnewood, Pennsylvania, United States

Medical University of South Carolina Charleston; 🇺🇸 Charleston, South Carolina, United States

Benaroya Virginia Mason; 🇺🇸 Seattle, Washington, United States

The Ottawa Hospital; 🇨🇦 Ottawa, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Canada

Herz- und Diabeteszentrum NRW - Bad Oeynhausen; 🇩🇪 Bad Oeynhausen, Germany

Universitätsklinikum Heidelberg Medizinische Klinik; 🇩🇪 Heidelberg, Germany

Johannes Gutenberg Universitaet Mainz; 🇩🇪 Mainz, Germany

Universitätsspital Basel; 🇨🇭 Basel, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland