RESPONDER-HF Trial

NCT05425459 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 2201
• Study Type: interventional
• Target: 750
• Locations: 6 countries
• Sites: 60

Brief Summary

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

Conditions

Heart Failure; Heart Failure, Diastolic

Keywords

Heart failure with preserved ejection fraction (HFpEF); Heart failure with midrange ejection fraction (HFmrEF); Interatrial Shunt

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• The incidence of cardiovascular mortality

  Up to 12 months

• The rate of time-to-cardiovascular mortality

  Up to 12 months

• The rate of major adverse cardiac periprocedural events

  Through 30 days

• The incidence of non-fatal, ischemic stroke

  Through 12 months

• The rate of new onset or worsening of kidney dysfunction

  Through 12 months

Study Arms (2)

Treatment

EXPERIMENTAL

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

Control

SHAM COMPARATOR

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)

Interventions

Corvia Atrial Shunt System / IASD System II 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.

Treatment

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

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

Control

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic symptomatic heart failure (HF) documented by the following:
• Symptoms of HF requiring current treatment with diuretics if tolerated for ≥ 30 days AND
• New York Heart Association (NYHA) class II; OR NYHA class III, or ambulatory NYHA class IV symptoms; AND
• ≥ 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
• 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
• Site determined echocardiographic LV ejection fraction ≥ 40% within the past 6 months, without documented ejection fraction \< 30% in the 5 years prior.
• Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following:
• Left Atrial (LA) diameter \> 4 cm; or
• Diastolic LA volume \> 50 or LA volume index \> 28 ml/m2 or
• Lateral e' \< 10 cm/s; or
• e' \< 8 cm/s; or
• 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.
• Resting RAP ≤ 14 mmHg
• Site determined hemodynamic evidence of peak exercise pulmonary vascular resistance (PVR) \< 1.75 Wood units
• Age ≥ 40 years old

You may not qualify if:

• Advanced heart failure defined as one or more of the below:
• ACC/AHA/European Society of Cardiology (ESC) Stage D heart failure, non-ambulatory NYHA Class IV HF
• Cardiac index \< 2.0 L/min/m2
• Inotropic infusion (continuous or intermittent) for EF \< 40% within the past 6 months
• Patient is on the cardiac transplant waiting list.
• Inability to perform 6-minute walk test (distance \< 50 meters), OR 6-minute walk test \> 600m
• 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)
• Right ventricular dysfunction, assessed by the site cardiologist and defined as one or more of the following:
• More than mild right ventricular (RV) dysfunction as estimated by transthoracic echocardiogram (TTE); OR
• TAPSE \< 1.4 cm; OR
• Right ventricular (RV) size ≥ left ventricular (LV) size as estimated by TTE; OR
• Ultrasound or clinical evidence of congestive hepatopathy; OR
• Evidence of RV dysfunction defined by TTE as an RV fractional area change \< 35%.
• Any implanted cardiac rhythm device
• 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:

Sponsors & Collaborators

• Corvia Medical: lead

Study Sites (61)

Arizona Cardiovascular Research Center

Phoenix, Arizona, 85016, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

MemorialCare Long Beach Medical Center

Long Beach, California, 90806, United States

Location

Christiana Care Health Services

Newark, Delaware, 19718, United States

Location

Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

NCH Naples

Naples, Florida, 34102, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Northside Hospital Gwinnett Campus

Lawrenceville, Georgia, 30046, United States

Location

Wellstar Kennestone

Marietta, Georgia, 30060, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Endeavor Health-Northshore

Glenview, Illinois, 60026, United States

Location

LSU Health Shreveport

Shreveport, Louisiana, 71103, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

UMass Memorial Hospital University Campus

Worcester, Massachusetts, 01655, United States

Location

University of Michigan Health Systems

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Weill Cornell

New York, New York, 10065, United States

Location

Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinatti Medical Center

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic OH

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner medical Center

Columbus, Ohio, 43210, United States

Location

St. Francis Hospital (Heart Hospital)

Tulsa, Oklahoma, 74136, United States

Location

OHSU Hospital

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Cardiovascular Institute (CVI) Research

Pittsburgh, Pennsylvania, 15212, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

North Central Heart-Avera

Sioux Falls, South Dakota, 57108, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

West Virginia Heart and Vascular

Morgantown, West Virginia, 26508, United States

Location

St. Vincents Hospital

Darlinghurst, New South Wales, Australia

Location

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

LKH University Clinic

Graz, 8047, Austria

Location

Onze-Lieve-Vrouwziekenhuis Aalst (OLV)

Aalst, B-9300, Belgium

Location

St. Paul's Hospital Providence Health Care

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Unity Health Toronto St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Heart Center Bad Krozingen

Bad Krozingen, 79189, Germany

Location

Kerckhoff Klinik

Bad Nauheim, Germany

Location

Hospital Charité - University Medicine Berlin

Berlin, 10117, Germany

Location

Vivantes Clinic Friedrichshain Berlin

Berlin, 10249, Germany

Location

DRK Clinics Berlin Koepenick

Berlin, 12559, Germany

Location

Unfallkrankenhaus Berlin

Berlin, Germany

Location

University Hospital Cologne

Cologne, 50937, Germany

Location

Heart Center of Dresden

Dresden, 01307, Germany

Location

UK Duesseldorf

Düsseldorf, Germany

Location

University Heart Center Freiburg

Freiburg im Breisgau, Germany

Location

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

Göttingen, Germany

Location

Marienkrankenhaus Hospital Hamburg

Hamburg, 22087, Germany

Location

Asklepios Clinic Altona Hamburg

Hamburg, 22763, Germany

Location

Herzzentrum Leipzig - Universitätsklinik

Leipzig, 04289, Germany

Location

University Hospital Schleswig-Holstein (UKSH) Luebeck

Lübeck, 23538, Germany

Location

University Hospital Münster

Münster, 48149, Germany

Location

Helios Kliniken Schwerin

Schwerin, 19049, Germany

Location

Ulm University Hospital

Ulm, 89081, Germany

Location

University Hospital Wurzburg

Würzburg, 97080, Germany

Location

UMCG - Groningen

Groningen, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 35354306 BACKGROUND

• 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.

  PMID: 35120593 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic

Interventions

Ice

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Water; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Environment and Public Health

Study Officials

• Sanjiv Shah, MD

  Northwestern Memorial Hospital

  PRINCIPAL INVESTIGATOR

• Martin Leon, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 21, 2022
• Study Start: November 17, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): March 1, 2031
• Last Updated: March 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); US (33); DE (19); BE (1); AU (4); CA (2)