RESPONDER-HF Trial

NCT ID: NCT05425459

Last Updated: 2025-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

750 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-17

Study Completion Date

2031-03-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Heart Failure Heart Failure, Diastolic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Corvia Atrial Shunt System / IASD System II

Intervention Type DEVICE

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.

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.

Group Type SHAM_COMPARATOR

Intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)

Intervention Type OTHER

Intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) for examination of the atrial septum and left atrium.

Interventions

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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.

Intervention Type DEVICE

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.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Corvia Medical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sanjiv Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern Memorial Hospital

Martin Leon, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Arizona Cardiovascular Research Center

Phoenix, Arizona, United States

Site Status RECRUITING

Scripps Clinic

La Jolla, California, United States

Site Status RECRUITING

MemorialCare Long Beach Medical Center

Long Beach, California, United States

Site Status RECRUITING

Christiana Care Health Services

Newark, Delaware, United States

Site Status RECRUITING

Memorial Regional Hospital

Hollywood, Florida, United States

Site Status RECRUITING

NCH Naples

Naples, Florida, United States

Site Status RECRUITING

Cleveland Clinic Florida

Weston, Florida, United States

Site Status RECRUITING

Northside Hospital Gwinnett Campus

Lawrenceville, Georgia, United States

Site Status RECRUITING

Wellstar Kennestone

Marietta, Georgia, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Endeavor Health-Northshore

Glenview, Illinois, United States

Site Status RECRUITING

LSU Health Shreveport

Shreveport, Louisiana, United States

Site Status RECRUITING

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States

Site Status RECRUITING

UMass Memorial Hospital University Campus

Worcester, Massachusetts, United States

Site Status RECRUITING

University of Michigan Health Systems

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status NOT_YET_RECRUITING

Weill Cornell

New York, New York, United States

Site Status RECRUITING

Christ Hospital

Cincinnati, Ohio, United States

Site Status RECRUITING

University of Cincinatti Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Cleveland Clinic OH

Cleveland, Ohio, United States

Site Status RECRUITING

Ohio State University Wexner medical Center

Columbus, Ohio, United States

Site Status RECRUITING

St. Francis Hospital (Heart Hospital)

Tulsa, Oklahoma, United States

Site Status RECRUITING

OHSU Hospital

Portland, Oregon, United States

Site Status RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Cardiovascular Institute (CVI) Research

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

North Central Heart-Avera

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Vanderbilt University

Nashville, Tennessee, United States

Site Status RECRUITING

Baylor St. Luke's Medical Center

Houston, Texas, United States

Site Status RECRUITING

University of Virginia

Charlottesville, Virginia, United States

Site Status RECRUITING

West Virginia Heart and Vascular

Morgantown, West Virginia, United States

Site Status RECRUITING

St. Vincents Hospital

Darlinghurst, New South Wales, Australia

Site Status RECRUITING

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Site Status RECRUITING

Prince Charles Hospital

Chermside, Queensland, Australia

Site Status RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

LKH University Clinic

Graz, , Austria

Site Status RECRUITING

Onze-Lieve-Vrouwziekenhuis Aalst (OLV)

Aalst, , Belgium

Site Status RECRUITING

St. Paul's Hospital Providence Health Care

Vancouver, British Columbia, Canada

Site Status RECRUITING

Unity Health Toronto St. Michael's Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

University Heart Center Bad Krozingen

Bad Krozingen, , Germany

Site Status RECRUITING

Kerckhoff Klinik

Bad Nauheim, , Germany

Site Status RECRUITING

Hospital Charité - University Medicine Berlin

Berlin, , Germany

Site Status RECRUITING

Vivantes Clinic Friedrichshain Berlin

Berlin, , Germany

Site Status RECRUITING

DRK Clinics Berlin Koepenick

Berlin, , Germany

Site Status RECRUITING

Unfallkrankenhaus Berlin

Berlin, , Germany

Site Status RECRUITING

University Hospital Cologne

Cologne, , Germany

Site Status RECRUITING

Heart Center of Dresden

Dresden, , Germany

Site Status RECRUITING

UK Duesseldorf

Düsseldorf, , Germany

Site Status RECRUITING

University Heart Center Freiburg

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Georg-August Universität Gottingen Universitätsklinikum Göttingen Klinik für Kardiologie und Pneumologie

Göttingen, , Germany

Site Status RECRUITING

Marienkrankenhaus Hospital Hamburg

Hamburg, , Germany

Site Status RECRUITING

Asklepios Clinic Altona Hamburg

Hamburg, , Germany

Site Status RECRUITING

Herzzentrum Leipzig - Universitätsklinik

Leipzig, , Germany

Site Status RECRUITING

University Hospital Schleswig-Holstein (UKSH) Luebeck

Lübeck, , Germany

Site Status RECRUITING

University Hospital Münster

Münster, , Germany

Site Status RECRUITING

Helios Kliniken Schwerin

Schwerin, , Germany

Site Status RECRUITING

Ulm University Hospital

Ulm, , Germany

Site Status RECRUITING

University Hospital Wurzburg

Würzburg, , Germany

Site Status RECRUITING

UMCG - Groningen

Groningen, , Netherlands

Site Status RECRUITING

Countries

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United States Australia Austria Belgium Canada Germany Netherlands

Central Contacts

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Jan Komtebedde, DVM

Role: CONTACT

978-654-6113

Karen Stephen, RN, BS

Role: CONTACT

618-604-2814

Facility Contacts

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Vijendra Swarup, MD

Role: primary

Katherine Palaeologus

Role: primary

Ann Marie Lenoir

Role: primary

Elisa Serantes

Role: primary

Linda Pastorious

Role: primary

Maria Mieja

Role: primary

Tamara Wakhisi

Role: primary

Stacey Mitchell

Role: primary

Daniel Roshevsky

Role: primary

Role: backup

Cynthia Arevalo

Role: primary

Karl Mendoza

Role: primary

847-503-6402

Tobie Leonards

Role: primary

Jean Byrne

Role: primary

Vijayadithyan Jaganathan

Role: primary

Joanna Wells

Role: primary

Madison Holk

Role: primary

Manuel Castillo

Role: primary

Alkouchiri Alkouchiri

Role: primary

Susanne Pasley

Role: primary

Rachael Mardis

Role: primary

Barbara Gus

Role: primary

Annie Kellum

Role: primary

Martha Dixon

Role: primary

Anna Garwood

Role: primary

Mckenna Krall

Role: primary

Laurie Machen

Role: primary

Elly Borhanian

Role: primary

Patty Eisenbraun

Role: primary

Sherron Crook

Role: primary

Claudell Montano

Role: primary

Linda Bryceland

Role: primary

Emma Norris

Role: primary

Anne Gordon

Role: primary

Maricel Roxas

Role: primary

Suzanna Barker

Role: primary

Andreas Praschk

Role: primary

Hedwiq Batjoens

Role: primary

Ulrike Maier

Role: primary

Elisabetha Gharib

Role: primary

Anja Gerstendberg-Eschment

Role: primary

Sylke Helms

Role: primary

Ana Heinrichs

Role: primary

Cecile Bosredion

Role: primary

Marion Redlefsen

Role: primary

Christine Neumann

Role: primary

Josephine Koch

Role: primary

Rosa Saraei

Role: primary

Lena Makowski

Role: primary

Pauline Herke

Role: primary

Olga Smirnova

Role: primary

Victoria Sokalski

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 35354306 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35120593 (View on PubMed)

Other Identifiers

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2201

Identifier Type: -

Identifier Source: org_study_id

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