RESPONDER-HF Trial
Purpose
Multicenter, Prospective, Randomized, Sham Controlled, Double Blinded Clinical Trial, with; 1:1 randomization
Conditions
- Heart Failure
- Heart Failure, Diastolic
Eligibility
- Eligible Ages
- Over 40 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Chronic symptomatic heart failure (HF) documented by the following: 1. Symptoms of HF requiring current treatment with diuretics if tolerated for ≥ 30 days AND 2. New York Heart Association (NYHA) class II; OR NYHA class III, or ambulatory NYHA class IV symptoms; AND 3. ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV) diuretics; or intensification of oral diuresis within the 12 months prior to study entry; OR an NT-proB-type Natriuretic Peptide (NT-pro BNP) value > 150 pg/ml in normal sinus rhythm, > 450 pg/ml in atrial fibrillation, or a brain natriuretic peptide (BNP) value > 50 pg/ml in normal sinus rhythm, > 150 pg/ml in atrial fibrillation within the past 6 months 2. Ongoing stable guideline-directed medical therapy (GDMT) HF management and management of comorbidities according to the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Heart Failure. Stable management includes a minimum period of 4 weeks post-hospitalization for any cause, including treatment with IV diuretics 3. Site determined echocardiographic LV ejection fraction ≥ 40% within the past 6 months, without documented ejection fraction < 30% in the 5 years prior. 4. Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following: 1. Left Atrial (LA) diameter > 4 cm; or 2. Diastolic LA volume > 50 or LA volume index > 28 ml/m2 or 3. Lateral e' < 10 cm/s; or 4. e' < 8 cm/s; or 5. Site determined elevated pulmonary capillary wedge pressure (PCWP) with a gradient compared to right atrial pressure (RAP) documented by end-expiratory PCWP during supine ergometer exercise ≥ 25 millimeters of mercury (mm Hg), and greater than RAP by ≥ 5 mm Hg. 6. Resting RAP ≤ 14 mmHg 7. Site determined hemodynamic evidence of peak exercise pulmonary vascular resistance (PVR) < 1.75 Wood units 8. Age ≥ 40 years old 9. Participant has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the Institutional Review Board (IRB) or Ethics Committee (EC) 10. Participant is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams 11. Transseptal catheterization and femoral vein access to the right atrium is determined to be feasible by site interventional cardiology investigator.
Exclusion Criteria
- Advanced heart failure defined as one or more of the below: 1. ACC/AHA/European Society of Cardiology (ESC) Stage D heart failure, non-ambulatory NYHA Class IV HF 2. Cardiac index < 2.0 L/min/m2 3. Inotropic infusion (continuous or intermittent) for EF < 40% within the past 6 months 4. Patient is on the cardiac transplant waiting list. 2. Inability to perform 6-minute walk test (distance < 50 meters), OR 6-minute walk test > 600m 3. The patient has verified that the ability to walk 6 minutes is limited primarily by joint, foot, leg, hip or back pain; unsteadiness or dizziness or lifestyle (and not by shortness of breath and/or fatigue and/or chest pain) 4. Right ventricular dysfunction, assessed by the site cardiologist and defined as one or more of the following: 1. More than mild right ventricular (RV) dysfunction as estimated by transthoracic echocardiogram (TTE); OR 2. TAPSE < 1.4 cm; OR 3. Right ventricular (RV) size ≥ left ventricular (LV) size as estimated by TTE; OR 4. Ultrasound or clinical evidence of congestive hepatopathy; OR 5. Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%. 5. Any implanted cardiac rhythm device 6. Structural heart repair aortic valve replacement (AVR) or mitral valve replacement (MVR) (surgical or percutaneous) within the past 12 months; planned valve intervention in the next 3 months, or presence of hemodynamically significant valve disease as assessed by the site cardiologist and defined as: 1. Mitral valve disease grade ≥ 3+ mitral regurgitation (MR) or > mild Mitral Stenosis (MS); OR 2. Tricuspid valve (TR) regurgitation grade ≥ 2+ TR; OR 3. Aortic valve disease ≥ 2+ aortic regurgitation (AR) or > moderate aortic stenosis (AS) 7. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation 8. Participants with existing or surgically closed (with a patch) atrial septal defects. Participants with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are not excluded 9. Myocardial Infarction (MI) and/or percutaneous cardiac intervention within past 3 months; Coronary Artery Bypass Graft (CABG) surgery in past 3 months or any planned cardiac interventions in the 3 months following enrollment. 10. Known clinically significant un-revascularized coronary artery disease, defined as: coronary artery stenosis with angina or other evidence of ongoing active coronary ischemia 11. Known clinically significant untreated carotid artery stenosis likely to require intervention 12. Atrial fibrillation with resting heart rate (HR) > 100 beats-per-minute (BPM) 13. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis) 14. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months 15. Participant is contraindicated to receive either dual antiplatelet therapy, or an oral anticoagulant; or has a documented coagulopathy 16. Anemia with Hemoglobin < 10 g/dl 17. Chronic pulmonary disease requiring continuous home oxygen, OR significant chronic pulmonary disease defined as forced expiratory volume (FEV)1 <1Liter 18. Resting arterial oxygen saturation < 95% on room air, <93% when residing at high altitude 19. Currently requiring dialysis; or estimated glomerular filtration rate eGFR < 25ml/min/1.73 m2 by chronic kidney disease (CKD) CKD-Epi equation 20. Systolic blood pressure > 170 mm Hg at screening 21. Significant hepatic impairment defined as 3 times upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase 22. Participants on significant immunosuppressive treatment or on systemic steroid treatment 23. Life expectancy less than 12 months for known non-cardiovascular reasons 24. Known hypersensitivity to nickel or titanium 25. Women of childbearing potential 26. Severe obstructive sleep apnea not treated with continuous positive airway pressure (CPAP) or other measures 27. Body Mass Index (BMI) > 45; BMI 40 - 45 is also excluded unless in the opinion of the investigator, vascular access can be obtained safely 28. Severe depression and/or anxiety 29. Currently participating in an investigational drug or device study that would interfere with the conduct or results of this study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational 30. In the opinion of the investigator, the Participant is not an appropriate candidate for the study.
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Treatment |
Participants randomized to the treatment arm will undergo a fluoroscopic and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and InterAtrial Shunt Device (IASD) System II implant procedure. |
|
|
Sham Comparator Control |
Participants randomized to the control arm will undergo fluoroscopy and intracardiac echocardiography from the femoral vein or transesophageal echocardiography, for examination of the atrial septum and left atrial appendage. |
|
Recruiting Locations
Arizona Cardiovascular Research Center
Phoenix 5308655, Arizona 5551752 85016
Phoenix 5308655, Arizona 5551752 85016
Contact:
Vijendra Swarup, MD
Vijendra Swarup, MD
Scripps Clinic
La Jolla 5363943, California 5332921 92037
La Jolla 5363943, California 5332921 92037
MemorialCare Long Beach Medical Center
Long Beach 5367929, California 5332921 90806
Long Beach 5367929, California 5332921 90806
Christiana Care Health Services
Newark 4143861, Delaware 4142224 19718
Newark 4143861, Delaware 4142224 19718
Memorial Regional Hospital
Hollywood 4158928, Florida 4155751 33021
Hollywood 4158928, Florida 4155751 33021
NCH Naples
Naples 4165565, Florida 4155751 34102
Naples 4165565, Florida 4155751 34102
Northside Hospital Gwinnett Campus
Lawrenceville 4205196, Georgia 4197000 30046
Lawrenceville 4205196, Georgia 4197000 30046
Wellstar Kennestone
Marietta 4207783, Georgia 4197000 30060
Marietta 4207783, Georgia 4197000 30060
Northwestern University
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60611
Contact:
Daniel Roshevsky
Daniel Roshevsky
University of Chicago Medical Center
Chicago 4887398, Illinois 4896861 60637
Chicago 4887398, Illinois 4896861 60637
Endeavor Health-Northshore
Glenview 4893886, Illinois 4896861 60026
Glenview 4893886, Illinois 4896861 60026
LSU Health Shreveport
Shreveport 4341513, Louisiana 4331987 71103
Shreveport 4341513, Louisiana 4331987 71103
Lahey Hospital & Medical Center
Burlington 4931737, Massachusetts 6254926 01805
Burlington 4931737, Massachusetts 6254926 01805
UMass Memorial Hospital University Campus
Worcester 4956184, Massachusetts 6254926 01655
Worcester 4956184, Massachusetts 6254926 01655
University of Michigan Health Systems
Ann Arbor 4984247, Michigan 5001836 48109
Ann Arbor 4984247, Michigan 5001836 48109
Mayo Clinic Rochester
Rochester 5043473, Minnesota 5037779 55905
Rochester 5043473, Minnesota 5037779 55905
Weill Cornell
New York 5128581, New York 5128638 10065
New York 5128581, New York 5128638 10065
Christ Hospital
Cincinnati 4508722, Ohio 5165418 45219
Cincinnati 4508722, Ohio 5165418 45219
University of Cincinatti Medical Center
Cincinnati 4508722, Ohio 5165418 45219
Cincinnati 4508722, Ohio 5165418 45219
Ohio State University Wexner medical Center
Columbus 4509177, Ohio 5165418 43210
Columbus 4509177, Ohio 5165418 43210
Contact:
Annie Kellum
Annie Kellum
St. Francis Hospital (Heart Hospital)
Tulsa 4553433, Oklahoma 4544379 74136
Tulsa 4553433, Oklahoma 4544379 74136
Thomas Jefferson University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19107
Philadelphia 4560349, Pennsylvania 6254927 19107
Cardiovascular Institute (CVI) Research
Pittsburgh 5206379, Pennsylvania 6254927 15212
Pittsburgh 5206379, Pennsylvania 6254927 15212
Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29403
Charleston 4574324, South Carolina 4597040 29403
North Central Heart-Avera
Sioux Falls 5231851, South Dakota 5769223 57108
Sioux Falls 5231851, South Dakota 5769223 57108
Vanderbilt University
Nashville 4644585, Tennessee 4662168 37235
Nashville 4644585, Tennessee 4662168 37235
Baylor St. Luke's Medical Center
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
University of Virginia
Charlottesville 4752031, Virginia 6254928 22908
Charlottesville 4752031, Virginia 6254928 22908
West Virginia Heart and Vascular
Morgantown 4815352, West Virginia 4826850 26508
Morgantown 4815352, West Virginia 4826850 26508
More Details
- NCT ID
- NCT05425459
- Status
- Recruiting
- Sponsor
- Corvia Medical
Detailed Description
Following supine bicycle exercise hemodynamic assessment to verify eligibility, patients are sedated then randomized to the treatment or control group. Patients in both arms will undergo placement of femoral venous access sheath. Patients randomized to the treatment arm will undergo a fluoroscopically and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and Corvia Atrial Shunt implant procedure. Patients randomized to the control arm will undergo ICE from the femoral vein or TEE for examination of the atrial septum and left atrium. Patients will be evaluated at pre-specified time intervals and followed for 5 years. All patients will be unblinded after the 24 month follow up visit.