Clinical trial NCT05686317: ALT-FLOW II Trial of the Edwards APTURE Transcatheter Shunt System
Official title: A Randomized, Sham-controlled Clinical Trial for Evaluation of the Edwards APTURE Transcatheter Shunt System (ALT-FLOW II)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2023-01-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: Device + Medical Therapy: Subjects with Early Major Adverse Events
timeFrame: 30 days
measure: Mean change in PCWL from baseline at 6 months
timeFrame: 6-months
Secondary outcomes:
measure: KCCQ-OSS change from baseline at 6-month follow-up
timeFrame: 6-months
measure: 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.
timeFrame: 6-months
measure: 6MWT change from baseline at 6-month follow-up
timeFrame: 6-months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: Elk Grove
country: United States
facility: Ascension Illinois Heart and Vascular Medical Group
state: Illinois
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital & Heart Center
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Oregon City
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina Charleston
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Benaroya Virginia Mason
state: Washington
city: Ottawa
country: Canada
facility: The Ottawa Hospital
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW - Bad Oeynhausen
city: Cologne
country: Germany
facility: Herzzentrum Universitätsklinikum Köln
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg Medizinische Klinik
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaet Mainz
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
Study officials:
References: