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

• ClinicalTrials.gov Identifier: NCT05686317
• Recruitment Status: Recruiting
• First Posted: January 17, 2023
• Last Update Posted: September 8, 2023
• Sponsor: Edwards Lifesciences
• Information provided by (Responsible Party): Edwards Lifesciences

Tracking Information

• First Submitted Date: January 6, 2023
• First Posted Date: January 17, 2023
• Last Update Posted Date: September 8, 2023
• Actual Study Start Date: April 1, 2023
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2023)

• Device + Medical Therapy: Subjects with Early Major Adverse Events [ Time Frame: 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 PCWP from baseline at 20W exercise [ Time Frame: 6-months ]
  Hemodynamic Effectiveness: change in PCWP at 20W exercise from baseline (mmHg) at 6 months.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: September 5, 2023)

• KCCQ-OSS change from baseline at 6-month follow-up [ Time Frame: 6-months ]
• 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. [ Time Frame: 6-months ]
• 6MWT change from baseline at 6-month follow-up [ Time Frame: 6-months ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Brief Summary: This is a prospective, multi-center, randomized, sham-controlled 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Device: Edwards APTURE transcatheter shunt system
  Treatment with APTURE shunt
• Diagnostic Test: Sham procedure
  CS angiography

Study Arms

• Experimental: APTURE shunt + medical therapy
  Intervention: Device: Edwards APTURE transcatheter shunt system
• Sham Comparator: Sham + medical therapy
  Intervention: Diagnostic Test: Sham procedure

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 7, 2023): 100
• Original Enrollment: Not Provided
• Estimated Study Completion Date: October 31, 2029
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Symptomatic heart failure

  • A primary diagnosis of HFmrEF or HFpEF (LVEF > 40%), and
  • NYHA class II to ambulatory NYHA class IV (IVa), and

• Documentation of at least one of the following from the date of initial informed consent:

  • ≥ 1 prior HF hospitalization(s) requiring IV HF therapy in the prior 12 months; AND/OR
  • EITHER BNP value > 35 pg/ml or > 125 pg/ml in permanent or long-term persistent atrial fibrillation; OR
  • NT-proBNP > 125 pg /ml or > 375 pg /ml in permanent or long-term persistent atrial fibrillation

• 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:

  o Pulmonary capillary wedge pressure at 20 Watts exercise (PCWP 20W) as measured at end-expiration is elevated to ≥ 25 mmHg and PCWP 20W exceeds right atrial pressure (RAP 20W) 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:

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

• Valve disease:

  • Degenerative mitral regurgitation > moderate
  • Functional or secondary mitral valve regurgitation defined as grade > moderate
  • Mitral stenosis > mild
  • Primary or secondary tricuspid valve regurgitation defined as grade > moderate
  • 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:

  • Tricuspid annular plane systolic excursion (TAPSE) <1.4 cm, or
  • RV size ≥ LV size
  • Right ventricular ejection fraction (RVEF) < 35%; OR
  • 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bridget Hurley; (949) 250-2265; bridget_hurley@edwards.com

Contact: Melissa Arteaga; (949) 250-2002; melissa_arteaga@edwards.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05686317
• Other Study ID Numbers: 2022-06
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Edwards Lifesciences
• Original Responsible Party: [Redacted]
• Current Study Sponsor: Edwards Lifesciences
• Original Study Sponsor: [Redacted]
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Edwards Lifesciences
• Verification Date: August 2023