RESPONDER-HF Trial

Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction (EF) Heart Failure (Protocol #2201)

Multicenter, Prospective, Randomized, Sham Controlled, Double Blinded Clinical Trial, with; 1:1 randomization

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Heart Failure, Diastolic
• Intervention / Treatment: Device: Corvia Atrial Shunt System / IASD System II; Other: Intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)

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.

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia
      • St. Vincents Hospital
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Austria
  • Graz, Austria, 8047
    • LKH University Clinic
• Belgium
  • Aalst, Belgium, B-9300
    • Onze-Lieve-Vrouwziekenhuis Aalst (OLV)
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital Providence Health Care
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health Toronto St. Michael's Hospital
• Germany
  • Bad Krozingen, Germany, 79189
    • University Heart Center Bad Krozingen
  • Bad Nauheim, Germany
    • Kerckhoff Klinik
  • Berlin, Germany
    • Unfallkrankenhaus Berlin
  • Berlin, Germany, 10117
    • Hospital Charité - University Medicine Berlin
  • Berlin, Germany, 10249
    • Vivantes Clinic Friedrichshain Berlin
  • Berlin, Germany, 12559
    • DRK Clinics Berlin Koepenick
  • Cologne, Germany, 50937
    • University Hospital Cologne
  • Dresden, Germany, 01307
    • Heart Center of Dresden
  • Düsseldorf, Germany
    • UK Duesseldorf
  • Freiburg im Breisgau, Germany
    • University Heart Center Freiburg
  • Göttingen, Germany
    • Georg-August Universität Gottingen Universitätsklinikum Göttingen Klinik für Kardiologie und Pneumologie
  • Hamburg, Germany, 22763
    • Asklepios Clinic Altona Hamburg
  • Hamburg, Germany, 22087
    • Marienkrankenhaus Hospital Hamburg
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig - Universitätsklinik
  • Lübeck, Germany, 23538
    • University Hospital Schleswig-Holstein (UKSH) Luebeck
  • Münster, Germany, 48149
    • University Hospital Münster
  • Schwerin, Germany, 19049
    • Helios Kliniken Schwerin
  • Ulm, Germany, 89081
    • Ulm University Hospital
  • Würzburg, Germany, 97080
    • University Hospital Wurzburg
• Netherlands
  • Groningen, Netherlands
    • UMCG - Groningen
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Cardiovascular Research Center
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Long Beach, California, United States, 90806
      • MemorialCare Long Beach Medical Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health Services
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
    • Naples, Florida, United States, 34102
      • NCH Naples
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Northside Hospital Gwinnett Campus
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center
    • Glenview, Illinois, United States, 60026
      • Endeavor Health-Northshore
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Shreveport
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Hospital University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Systems
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinatti Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic OH
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • St. Francis Hospital (Heart Hospital)
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Cardiovascular Institute (CVI) Research
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • North Central Heart-Avera
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor St. Luke's Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • West Virginia
    • Morgantown, West Virginia, United States, 26508
      • West Virginia Heart and Vascular

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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:

1. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Device: Corvia Atrial Shunt System / IASD System II; The primary component of the system is an implant placed in the atrial septum designed to allow left to right flow between the left atrium and right atrium to reduce the elevated left atrial pressure.
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.	Other: Intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE); Intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) for examination of the atrial septum and left atrium.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Primary Endpoint	The primary endpoint is a composite of heart failure event rates and Kansas City Cardiomyopathy Questionnaire (KCCQ) at 12 months. Responses are given on a Likert scale that for each individual item is scored on a scale of 0-100 with higher scores indicating better health.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of cardiovascular mortality	The incidence of cardiovascular mortality through 12 months.	Up to 12 months
The rate of time-to-cardiovascular mortality	Time-to-cardiovascular mortality through 12 months.	Up to 12 months
The rate of major adverse cardiac periprocedural events	Major adverse cardiac periprocedural events through 30 days defined as: Cardiac death; Myocardial infarction; Cardiac tamponade; Emergency cardiac surgery.	Through 30 days
The incidence of non-fatal, ischemic stroke	Incidence of non-fatal, ischemic stroke	Through 12 months
The rate of new onset or worsening of kidney dysfunction	New onset or worsening of kidney dysfunction (defined as estimated glomerular filtration rate (eGFR) decrease of > 20 ml/min/1.73 m2) through 12 months	Through 12 months
The incidence of thrombo-embolic complications including transient ischaemic attack (TIA) and systemic embolization)	The incidence of thrombo-embolic complications (TIA and systemic embolization) through 12 months	Through 12 months
The incidence of newly acquired persistent or permanent atrial fibrillation (AF) or atrial flutter	The incidence of newly acquired persistent or permanent AF or atrial flutter	Through 12 months
The incidence of participants with a ≥30% decrease in Tricuspid Annular Plane Systolic Excursion (TAPSE)	The incidence of participants with a ≥30% decrease Tricuspid Annular Plane Systolic Excursion (TAPSE)	Through 12 months
The rate of heart failure (HF) admissions	Total rate (first plus recurrent) per patient year of heart failure (HF) admissions or healthcare facility visits for intravenous diuresis or urgent visits with intensification of oral diuresis for HF through 24 months, analyzed when the last randomized participant completes 12 months follow-up.	Through 24 months
The change in New York Heart Association (NYHA) Class	Change in NYHA functional Class between baseline and 12 months	12 months
The change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score between baseline and 12 months, categorized as proportion of patients with changes of ≤0, >0 - 5, >5 - 10, >10 - 15, >15 - 20, >20 - 25, >25 points. Responses are given on a Likert scale that for each individual item is scored on a scale of 0-100 with higher scores indicating better health	12 months

Collaborators and Investigators

• Sponsor: Corvia Medical
• Investigators: Principal Investigator: Sanjiv Shah, MD, Northwestern Memorial Hospital; Principal Investigator: Martin Leon, MD, Columbia University

Publications and helpful links

General Publications

• Shah SJ, Borlaug BA, Chung ES, Cutlip DE, Debonnaire P, Fail PS, Gao Q, Hasenfuss G, Kahwash R, Kaye DM, Litwin SE, Lurz P, Massaro JM, Mohan RC, Ricciardi MJ, Solomon SD, Sverdlov AL, Swarup V, van Veldhuisen DJ, Winkler S, Leon MB; REDUCE LAP-HF II investigators. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet. 2022 Mar 19;399(10330):1130-1140. doi: 10.1016/S0140-6736(22)00016-2. Epub 2022 Feb 1.
• Borlaug BA, Blair J, Bergmann MW, Bugger H, Burkhoff D, Bruch L, Celermajer DS, Claggett B, Cleland JGF, Cutlip DE, Dauber I, Eicher JC, Gao Q, Gorter TM, Gustafsson F, Hayward C, van der Heyden J, Hasenfuss G, Hummel SL, Kaye DM, Komtebedde J, Massaro JM, Mazurek JA, McKenzie S, Mehta SR, Petrie MC, Post MC, Nair A, Rieth A, Silvestry FE, Solomon SD, Trochu JN, Van Veldhuisen DJ, Westenfeld R, Leon MB, Shah SJ; REDUCE LAP-HF-II Investigators. Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure. Circulation. 2022 May 24;145(21):1592-1604. doi: 10.1161/CIRCULATIONAHA.122.059486. Epub 2022 Mar 31.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Heart failure with preserved ejection fraction (HFpEF); Heart failure with midrange ejection fraction (HFmrEF); Interatrial Shunt
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Diastolic; Environment and Public Health; Inorganic Chemicals; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Oxides; Oxygen Compounds; Water; Ice
• Other Study ID Numbers: 2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes