FROST-HF: Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study
Study Details
Study Description
Brief Summary
The purpose of this clinical study is to assess the safety and effectiveness of the Atrial Flow Regulator in the treatment of subjects, 18 years of age or older, who have symptomatic heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) while on stable guideline directed medical therapy (GDMT) as outlined in the Guidelines for the Management of Heart Failure.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Randomization to 8mm AFR device AFR Device 8mm vs Sham procedure |
Device: Atrial Flow Regulator
Subjects will be randomized 1:1:1 where subjects will either receive the 8mm AFR device, 10mm AFR device or Sham procedure.
Other Names:
|
| Active Comparator: Randomization to 10mm AFR device AFR device vs Sham procedure |
Device: Atrial Flow Regulator
Subjects will be randomized 1:1:1 where subjects will either receive the 8mm AFR device, 10mm AFR device or Sham procedure.
Other Names:
|
| Sham Comparator: Randomization to sham procedure Sham procedure to AFR device (8mm or 10mm) |
Device: Sham Comparator
Subjects will be randomized 1:1:1 where subjects will either receive the 8mm AFR device, 10mm AFR device or Sham procedure.
|
Outcome Measures
Primary Outcome Measures
- Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months [Baseline through 12 months]
Incidence of and time to MACNE within 12 months. MACNE includes all-cause mortality, stroke, systemic embolism, open cardiac surgery or major endovascular repair, and major bleeding (BARC 3-5).
- Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality [Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.]
Incidence of and time to cardiovascular mortality through 12-24 months
- Composite Primary Efficacy Endpoint - Frequency of heart transplant or Left Ventricular Assist Device (LVAD) [Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.]
Incidence of and time to heart transplant or LVAD
- Composite Primary Efficacy Endpoint - Total rate of Heart Failure Hospitalizations [Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.]
Total rate (first plus recurrent) per patient year of heart failure hospitalization admissions and time to first heart failure hospitalizations through 12-24 months
- Composite Primary Efficacy Endpoint - KCCQ Score [Baseline through 6 months. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.]
Change in baseline KCCQ total summary score at 6-months
Secondary Outcome Measures
- Clinical performance - change from baseline in NYHA Classification [Baseline through end of study, approximately 5 years]
Clinical performance assessed by the change from baseline in NYHA Classification
- Clinical performance - change from baseline using KCCQ [Baseline through end of study, approximately 5 years]
Clinical performance assessed by the change from baseline using KCCQ
- Clinical performance - change from baseline using EQ-5D [Baseline through end of study, approximately 5 years]
Clinical performance assessed by the change from baseline using EQ-5D
- Clinical performance - change from baseline using the 6 Minute Walk Test (MWT) [Baseline through end of study, approximately 5 years]
Clinical performance assessed by the change from baseline using the 6 Minute Walk Test (MWT)
- Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement). [Baseline through 24 Months]
Analysis on components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).
- Components of Device Performance- Device placed in-situ as assessed by Investigator [Implant through end of study, approximately 5 years]
Analysis on components of device performance (Device placed in-situ as assessed by Investigator)
- Components of Device Performance - Patency: Evidence of left to right shunt through AFR device [Implant through end of study, approximately 5 years]
Analysis on components of device performance- Patency: Evidence of left to right shunt through AFR device as assessed by core lab
- Components of Device Performance- Implant embolization and clinically significant device migration [Implant through end of study, approximately 5 years]
Analysis on components of device performance- Implant embolization and clinically significant device migration (i.e. SAEs probably related to device).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Written informed consent
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Aged ≥18 years
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Presence of chronic symptomatic HF (NYHA ≥class 2) and at least one of the following:
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Prior heart failure hospitalization within 6 months of informed consent, or
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Increased NT-proBNP
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If LVEF documented at screening is >55%, then must have one of either:
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Left atrial enlargement (LA diameter >2.3 cm/m2 or LA volume index >28 mL/m2), or
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PCWP ≥ 15mmHg at rest within previous 12 months, or
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LVEDP ≥15mmHg at rest within previous 12 months
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6MWT
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Patients need to have maximally tolerated class 1 GDMT according to latest applicable guidelines (e.g., AHA or ESC), including CRT if appropriate, and a stable (no more than 100% increase or 50% decrease) dose diuretic.
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Using an acceptable method of contraception (for subjects of childbearing potential). Women of child-bearing potential will have a negative pregnancy test within 1 week of randomization.
Exclusion Criteria:
- General Exclusion Criteria
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Myocardial infarction and/or revascularization with percutaneous intervention (PCI) or coronary artery bypass grafting (CABG) within 3 months prior to informed consent
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Surgical or transcatheter valve (aortic, mitral, or tricuspid) repair or replacement within 2 months prior to informed consent
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Automated implantable cardioverter defibrillator (AICD) placement within 2 months prior to informed consent
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History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within 6 months prior to informed consent
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Advanced heart failure defined as current ACC/AHA Stage D heart failure
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Clinically significant valvular disease:
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mitral valve regurgitation grade ≥3+ MR, or
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tricuspid valve regurgitation grade ≥3+ TR, or
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aortic valve disease ≥3+ AR or ≥ moderate AS
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Uncontrolled hypertension, Systolic Blood Pressure (SBP) ≥160 or Diastolic Blood Pressure (DBP) ≥100 mmHg despite medical therapy at the time of screening visit
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Known clinically significant untreated carotid artery stenosis likely to require intervention, at discretion of investigator
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Current untreated coronary artery disease with indication for revascularization
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Any condition that limits exercise tolerance other than heart failure (e.g., peripheral vascular disease, orthopedic issues, angina, other)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Occlutech International AB
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- G210281