Heart Failure With Preserved Ejection Fraction (HFpEF)FROST-HFNCT05136820

Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study

A study testing Atrial Flow Regulator in people with Heart Failure With Preserved Ejection Fraction (HFpEF) and Heart Failure With Reduced Ejection Fraction (HFrEF), run by Occlutech International AB at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure With Preserved Ejection Fraction (HFpEF), Heart Failure With Reduced Ejection Fraction (HFrEF)
What is being tested?: Atrial Flow Regulator
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 15 participants
Where: 2 sitesUnited States
Study dates: 9 Mar 2023to Feb 2029
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

General Inclusion Criteria:

Aged ≥18 years
Presence of chronic symptomatic HF (NYHA ≥class 2) and at least one of the following:

Previous heart failure hospitalization within 6 months of informed consent or
Elevated NT-proBNP (or BNP):
If in Sinus Rhythm, must have a corrected elevated Brain Natriuretic Peptide (BNP) level of at least 300 pg/mL or an N-terminal pro-BNP (NT-proBNP) level of at least 900 pg/mL, according to local measurement, within 2 months of the Screening Visit during a clinically stable period*.
If in Atrial Fibrillation or Atrial Flutter, must have a corrected elevated BNP level of at least 400 pg/mL or an NT-proBNP level of at least 1200 pg/mL within 2 months of the Screening Visit during a clinically stable period*.

If LVEF documented at screening is >55%, then must have one of either:

Left atrial enlargement (LA diameter >2.3 cm/m2 or LA volume index >28 mL/m2), or
PCWP ≥ 15 mmHg at rest within previous 12 months, or
LVEDP ≥15 mmHg at rest within previous 12 months

6 MWT distance 100-450 meters
Treated with maximally tolerated doses of class I GDMT and class electrical therapies (CRT and ICD) according to latest applicable guidelines (e.g., AHA or ESC) for at least 2 months prior to informed consent, and a stable dose diuretic for at least 1 month prior to informed consent.

General Exclusion Criteria:

Myocardial infarction and/or revascularization with percutaneous intervention (PCI) or coronary artery bypass grafting (CABG) within 3 months prior to informed consent
Surgical or transcatheter valve (aortic, mitral, or tricuspid) repair or replacement within 2 months prior to informed consent
Automated implantable cardioverter defibrillator (AICD) placement within 2 months prior to informed consent
Resynchronization therapy started within 3 months prior to informed consent
Major surgery within 3 months prior to informed consent
History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within 6 months prior to informed consent, or any prior stroke with persistent neurologic deficit, or any prior intracranial bleed, or known intracerebral aneurysm, AV malformation or other intracranial pathology increasing the risk of bleeding
Uncontrolled atrial fibrillation with resting heart rate >110 beats per minute despite medical therapy
Documented history of non-dilated cardiomyopathy (obstructive hypertrophic, restrictive, infiltrative) or pericardial disease
Clinically significant valvular heart disease:

regurgitation grade ≥3+ or
severe stenosis of mitral or tricuspid valves, or
moderate or greater stenosis of aortic valves

Prior diagnosis of pulmonary hypertension with current treatment with one or more pulmonary hypertension specific drugs (e.g. endothelin receptor antagonists (ERAs), phosphodiesterase inhibitors (PDE 5 Inhibitors) or prostacyclin analogues)
Uncontrolled hypertension, Systolic Blood Pressure (SBP) ≥160 or Diastolic Blood Pressure (DBP) ≥100 mmHg despite medical therapy at the time of screening visit
Previous interventional or surgical atrial septal defect (ASD) or patent foramen ovale (PFO) closure
Inadequate vascular access for implantation of shunt, e.g., suboptimal femoral venous access for transseptal catheterization or inferior vena cava (IVC) is not patent
Chronic kidney disease currently requiring dialysis
Allergy or contraindication to aspirin, or clopidogrel and prasugrel and ticagrelor, or heparin and bivalirudin
Bleeding disorders (international normalized ratio [INR] >2.0, platelet count <100,000 x 109/L, hemoglobin <10.0 g/dL)
Known clinically significant untreated carotid artery stenosis likely to require intervention, at discretion of investigator
Current untreated coronary artery disease with indication for revascularization
Significant Right Ventricular dysfunction demonstrated by:

Tricuspid Annular Plane Systolic Excursion (TAPSE) <16mm or
Right Ventricular Fractional Area Change (RVFAC) ≤30%

Right Atrial Volume Index (RAVI) > 31ml/m2
Left Ventricular End-Diastolic Diameter (LVEDD) > 8.0 cm as assessed by echocardiography
Severe COPD requiring oral steroid therapy or daytime oxygen
Echocardiographic evidence of intra-cardiac mass, thrombus, or vegetation
On current immunosuppression or systemic oral steroid treatment
Any condition that limits exercise tolerance other than heart failure (e.g., peripheral vascular disease, orthopedic issues, angina, other), at the discretion of the Investigator

Trial locations and contacts

2 sites in 1 country.

United States2 sites

North Shore Northwell University Hospital Lenox Hill
New York, New York, 10075
Arizona Heart Rhythm Center
Phoenix, Arizona, 85016

Other trials in United States

About this study

Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF), Heart Failure With Reduced Ejection Fraction (HFrEF)
Being tested: Atrial Flow Regulator, Sham Comparator
Keywords: Heart Failure, Preserved Ejection Fraction, Reduced Ejection Fraction, HFpEF, HFrEF
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Atrial Flow RegulatorDevice
Also called AFR
Subjects will be randomized 1:1:1 where subjects will either receive the 6mm AFR device, 8mm AFR device or Sham procedure.
Sham ComparatorDevice
Subjects will be randomized 1:1:1 where subjects will either receive the 6mm AFR device, 8mm AFR device or Sham procedure.

Study groups in NCT05136820
Study group	Role	What they receive
Randomization to 6mm AFR device	Active comparator	AFR Device 6mm vs Sham procedure Receives: Device: Atrial Flow Regulator
Randomization to 8mm AFR device	Active comparator	AFR device 8mm vs Sham procedure Receives: Device: Atrial Flow Regulator
Randomization to sham procedure	Sham comparator	Sham procedure to AFR device (6mm or 8mm) Receives: Device: Sham Comparator
Roll-in Arm	Other	Patients in the Roll-in Arm will receive the AFR device Receives: Device: Atrial Flow Regulator

What is being measured

The primary outcome is the main question the study is designed to answer.

Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months
The Primary Safety Endpoint is defined as Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months of randomization. MACNE includes all-cause mortality, stroke, systemic thromboembolism, open cardiac surgery or major endovascular repair, and major bleeding (BARC 3-5).
Measured: Baseline through 12 months
Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality
Incidence of and time to cardiovascular mortality through 12-24 months
Measured: 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.
Composite Primary Efficacy Endpoint - Frequency of heart transplant or Left Ventricular Assist Device (LVAD)
Incidence of and time to heart transplant or LVAD
Measured: 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.
Composite Primary Efficacy Endpoint - Total rate of Heart Failure Hospitalizations
Total rate (first plus recurrent) per patient year of heart failure hospitalization admissions and time to first heart failure hospitalizations through 12-24 months
Measured: 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.
Composite Primary Efficacy Endpoint - Total rate of Heart Failure Treatment Intensification
Total rate (first plus recurrent) per patient year of heart failure treatment intensification event and time-to-first heart failure treatment intensification event through 12-24 months
Measured: 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.
Composite Primary Efficacy Endpoint - KCCQ Score
Change in baseline KCCQ total summary score at 6-months
Measured: Baseline through 6 months. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up.

Secondary outcomes (8)

Clinical performance - change from baseline in NYHA Classification
Clinical performance assessed by the change from baseline in NYHA Classification
Measured: Baseline through end of study, approximately 5 years
Clinical performance - change from baseline using KCCQ
Clinical performance assessed by the change from baseline using KCCQ
Measured: Baseline through end of study, approximately 5 years
Clinical performance - change from baseline using EQ-5D
Clinical performance assessed by the change from baseline using EQ-5D
Measured: Baseline through end of study, approximately 5 years
Clinical performance - change from baseline using the 6 Minute Walk Test (MWT)
Clinical performance assessed by the change from baseline using the 6 Minute Walk Test (MWT)
Measured: Baseline through end of study, approximately 5 years
Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).
Analysis on components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).
Measured: Baseline through 24 Months
Components of Device Performance- Device placed in-situ as assessed by Investigator
Analysis on components of device performance (Device placed in-situ as assessed by Investigator)
Measured: Implant through end of study, approximately 5 years
Components of Device Performance - Patency: Evidence of left to right shunt through AFR device
Analysis on components of device performance- Patency: Evidence of left to right shunt through AFR device as assessed by core lab
Measured: Implant through end of study, approximately 5 years
Components of Device Performance- Implant embolization and clinically significant device migration
Analysis on components of device performance- Implant embolization and clinically significant device migration (i.e. SAEs probably related to device).
Measured: Implant through end of study, approximately 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Mar 2023Feb 2029

First posted29 Nov 2021
Study start9 Mar 2023
Primary completionFeb 2026 (estimated)
Study completionFeb 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Heart Failure With Preserved Ejection Fraction (HFpEF)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Patients will be identified from the investigator's pool of heart failure patients who are symptomatic on stable guideline directed medical therapy. An electronic randomization scheme in the EDC system will be used to minimize risk of bias in the investigation
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05136820
Sponsor's protocol ID: G210281
Acronym: FROST-HF
Status last verified: Aug 2025
First submitted: 11 Nov 2021
Last updated: 8 Aug 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
Recruiting
Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
Recruiting
ELEVATE-HFpEF Clinical Study
Heart Failure With Preserved Ejection Fraction (HFpEF)
RecruitingPhase 2
The Clinical Trial of Tamibarotene for Patients With HFpEF (RELIEF Trial)
HFpEF - Heart Failure With Preserved Ejection Fraction

All Heart Failure With Preserved Ejection Fraction (HFpEF) trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study
ClinicalTrials.gov ID: NCT05136820
Acronym / sponsor ID: FROST-HF / G210281
Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF), Heart Failure With Reduced Ejection Fraction (HFrEF)
Keywords: Heart Failure, Preserved Ejection Fraction, Reduced Ejection Fraction, HFpEF, HFrEF
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 15 participants (actual)
Lead sponsor: Occlutech International ABIndustry (pharma, biotech, devices)
Study start: 9 Mar 2023 (actual)
Primary completion: Feb 2026 (estimated)
Study completion: Feb 2029 (estimated)
First posted: 29 Nov 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: Patients will be identified from the investigator's pool of heart failure patients who are symptomatic on stable guideline directed medical therapy. An electronic randomization scheme in the EDC system will be used to minimize risk of bias in the investigation

Arm	Type	Receives
Randomization to 6mm AFR device	Active comparator	Device: Atrial Flow RegulatorAFR Device 6mm vs Sham procedure
Randomization to 8mm AFR device	Active comparator	Device: Atrial Flow RegulatorAFR device 8mm vs Sham procedure
Randomization to sham procedure	Sham comparator	Device: Sham ComparatorSham procedure to AFR device (6mm or 8mm)
Roll-in Arm	Other	Device: Atrial Flow RegulatorPatients in the Roll-in Arm will receive the AFR device

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Atrial Flow RegulatorAlso: AFRSubjects will be randomized 1:1:1 where subjects will either receive the 6mm AFR device, 8mm AFR device or Sham procedure.	Device	Randomization to 6mm AFR device, Randomization to 8mm AFR device, Roll-in Arm
Sham ComparatorSubjects will be randomized 1:1:1 where subjects will either receive the 6mm AFR device, 8mm AFR device or Sham procedure.	Device	Randomization to sham procedure

Primary outcome

Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months
Time frame: Baseline through 12 months
The Primary Safety Endpoint is defined as Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months of randomization. MACNE includes all-cause mortality, stroke, systemic thromboembolism, open cardiac surgery or major endovascular repair, and major bleeding (BARC 3-5).
Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality
Time frame: 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)
Time frame: 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
Time frame: 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 - Total rate of Heart Failure Treatment Intensification
Time frame: 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 treatment intensification event and time-to-first heart failure treatment intensification event through 12-24 months
Composite Primary Efficacy Endpoint - KCCQ Score
Time frame: 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

8 secondary outcomes

Clinical performance - change from baseline in NYHA Classification
Time frame: Baseline through end of study, approximately 5 years
Clinical performance - change from baseline using KCCQ
Time frame: Baseline through end of study, approximately 5 years
Clinical performance - change from baseline using EQ-5D
Time frame: Baseline through end of study, approximately 5 years
Clinical performance - change from baseline using the 6 Minute Walk Test (MWT)
Time frame: Baseline through end of study, approximately 5 years
Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).
Time frame: Baseline through 24 Months
Components of Device Performance- Device placed in-situ as assessed by Investigator
Time frame: Implant through end of study, approximately 5 years
Components of Device Performance - Patency: Evidence of left to right shunt through AFR device
Time frame: Implant through end of study, approximately 5 years
Components of Device Performance- Implant embolization and clinically significant device migration
Time frame: Implant through end of study, approximately 5 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2025.
Individual participant dataSharing planned: No

Related trials for Heart Failure With Preserved Ejection Fraction (HFpEF)

Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
Recruiting
Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
Recruiting
ELEVATE-HFpEF Clinical Study
Heart Failure With Preserved Ejection Fraction (HFpEF)
RecruitingPhase 2
The Clinical Trial of Tamibarotene for Patients With HFpEF (RELIEF Trial)
HFpEF - Heart Failure With Preserved Ejection Fraction

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Megan Coylewright, MD, MPH, FSCAI, FACC principal investigator

Erlanger Health System

Muthiah Vaduganathan, MD, MPH principal investigator

Brigham and Women's Hospital Heart and Vascular Center

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months (time frame: Baseline through 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05136820.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2025.