REDUCE LAP-HF TRIAL II

NCT03088033 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 1601
• Study Type: interventional
• Target: 608
• Locations: 14 countries
• Sites: 90

Brief Summary

Multicenter, Prospective, Randomized Controlled, Blinded Trial, with a Non-implant Control group; 1:1 randomization.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Composite Primary Endpoint

  The primary endpoint is the composite of (a) incidence of and time-to-cardiovascular mortality or first non-fatal, ischemic stroke through 12 months; (b) total rate (first plus recurrent) per patient year of heart failure (HF) events, defined as hospital admissions, acute healthcare facility visits or urgent unscheduled outpatient visits for IV diuresis or intensification of oral diuretics for HF up to 24 months, analyzed when the last randomized subject completes 12 months follow-up, and time-to-first HF event; and (c) change in baseline KCCQ total summary score at 12 months.

  Up to 24 months

Secondary Outcomes (4)

• Composite safety endpoint defined as follows:

  12 months

• Rate of heart failure admissions

  Up to 24 months

• Change in NYHA Class

  12 months

• Change in Kansas City Cardiomyopathy Questionnaire

  12 months

Study Arms (2)

Treatment

EXPERIMENTAL

Patients randomized to the treatment arm will undergo a fluoroscopically and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and IASD System II implant procedure.

Device: IASD System II implant

Control

SHAM COMPARATOR

Patients randomized to the control arm will undergo ICE from the femoral vein or TEE for examination of the atrial septum and left atrium.

Other: intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)

Interventions

IASD System II implant 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 one or more of the following:
• Symptoms of HF requiring current treatment with diuretics for ≥ 30 days AND
• NYHA class II with a history of \> NYHA class II; OR NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening; or signs (any rales post cough, chest x-ray demonstrating pulmonary congestion,) within past 12 months; AND
• ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV), or intensification of oral diuresis for HF in a healthcare facility within the 12 months prior to study entry; OR an NT-pro BNP value \> 150 pg./ml in normal sinus rhythm, \> 450 pg./ml in atrial fibrillation, or a BNP value \> 50 pg./ml in normal sinus rhythm, \> 150 pg./ml in atrial fibrillation within the past 6 months.
• Ongoing stable GDMT HF management and management of potential comorbidities according to the 2013 ACCF/AHA Guidelines for the management of Heart Failure (with no significant changes \[\>100% increase or 50% decrease\], excluding diuretic dose change for a minimum of 4 weeks prior to screening) that is expected to be maintained without change for 6 months
• Age ≥ 40 years old, LV ejection fraction (EF) ≥ 40% within the past 3 months, without previously documented EF \<30% (within the past 3 years)
• Elevated PCWP with a gradient compared to right atrial pressure (RAP), documented by end-expiratory PCWP during supine ergometer exercise ≥ 25mmHg, and greater than RAP by ≥ 5 mmHg

You may not qualify if:

• MI and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization; AVR (surgical AVR or TAVR) within the past 12 months.
• Cardiac Resynchronization Therapy initiated within the past 6 months
• Advanced heart failure defined as one or more of the below:
• ACC/AHA/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 m), OR 6 minute walk test \> 600m
• History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
• Presence of significant valve disease defined by the site cardiologist as:
• Mitral valve regurgitation defined as grade ≥ 3+ MR
• Tricuspid valve regurgitation defined as grade ≥ 2+ TR
• Aortic valve disease defined as ≥ 2+ AR or \> moderate AS
• Known clinically significant untreated carotid artery stenosis likely to require intervention
• Currently requiring dialysis; or estimated-GFR \<25ml/min/1.73 m2 by CKD-Epi equation

Sponsors & Collaborators

• Corvia Medical: lead

Study Sites (91)

Arizona Cardiovascular Research Center

Phoenix, Arizona, 85016, United States

Location

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

Kaiser Permanente San Diego

La Jolla, California, 92120, United States

Location

Kaiser Permanente San Francisco Medical Center

San Francisco, California, 94115, United States

Location

South Denver Cardiology Associates

Littleton, Colorado, 80120, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33307, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Tallahassee Research Institute, Inc.

Tallahassee, Florida, 33208, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Evanston Northshore Healthcare

Evanston, Illinois, 60201, United States

Location

Cardiovascular Institute of the South

Houma, Louisiana, 70360, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Tufts New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 41809, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. Louis Heart and Vascular

St Louis, Missouri, 63136, United States

Location

Hackensack University Medical Center

Hamilton, New Jersey, 08690, United States

Location

Morristown Memorial Hospital

Morristown, New Jersey, 07962, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27157, United States

Location

Christ Hospital Ohio Heart and Vascular Institute

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University College of Medicine

Columbus, Ohio, 43210, United States

Location

Ohio Health

Columbus, Ohio, 43214, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17602, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37242, United States

Location

Baylor University Medical Center, Dallas

Dallas, Texas, 75246, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Concord Hospital

Camperdown, New South Wales, 2050, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

Location

St. Vincent Hospital

Sydney, New South Wales, 2010, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Medizinische Universität Graz

Graz, Austria

Location

OLVZ Aalst

Aalst, Belgium

Location

Az Sint-Jan Brugge

Bruges, Belgium

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

University Hospital Center, Zagreb

Zagreb, Croatia

Location

Rigshospitalet

Copenhagen, Denmark

Location

CHU de Dijon

Dijon, France

Location

CHU de Nantes

Nantes, France

Location

Hôpital Bichat

Paris, France

Location

Hôpital La Pitié Salpétrière

Paris, France

Location

CHU de Rennes

Rennes, France

Location

CHU de Rouen

Rouen, France

Location

Kerckhoff Klinik

Bad Nauheim, Germany

Location

Charite Universitatsmedizin Berlin

Berlin, Germany

Location

Unfallkrankenhaus Berlin

Berlin, Germany

Location

Universitatklinikum Duseldorf

Düsseldorf, Germany

Location

Heart Center Freiburg University

Freiburg im Breisgau, Germany

Location

Georg-August-Universitat

Göttingen, Germany

Location

Cardiologicum CRC

Hamburg, Germany

Location

UKE Hamburg

Hamburg, Germany

Location

University of Heidelberg

Heidelberg, Germany

Location

Heart Center of the University of Leipzig

Leipzig, Germany

Location

Klinikum der Universität Munchen

Munich, Germany

Location

University of Milano

Milan, Italy

Location

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

The Hospital of Hyogo College of Medicine

Hyōgo, Japan

Location

Nara Medical University Hospital

Nara, Japan

Location

National Cerebral and Cardiovascular Center

Osaka, Japan

Location

Osaka University Hospital

Osaka, Japan

Location

The University of Tokyo Hospital

Tokyo, Japan

Location

Tottori University Hospital

Tottori, Japan

Location

Toyama University Hospital

Toyama, Japan

Location

VU University Medical Center

Amsterdam, Netherlands

Location

UMC Groningen

Groningen, Netherlands

Location

Maastricht UMC Hart & Vaat Centrum

Maastricht, Netherlands

Location

St Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Fourth Military Hospital

Wroclaw, Poland

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

Golden Jubilee Hospital

Glasgow, United Kingdom

Location

Guys & St Thomas NHS Foundation Trust

London, United Kingdom

Location

Related Publications (7)

• Chaudhary RS, Hussain SMD, Wang YS, Komtebedde J, Hasenfuss G, Borlaug BA, Kaye DM, Cleland JGF, Leon MB, Shah SJ, van Veldhuisen DJ, Solomon SD, Cikes M, Cutlip DE. Expanded Definition of Worsening Heart Failure: Impact on Clinical Outcomes and Quality-of-Life Assessment. JACC Heart Fail. 2025 Sep;13(9):102571. doi: 10.1016/j.jchf.2025.102571. Epub 2025 Jul 25.

  PMID: 40714684 DERIVED

• Litwin SE, Komtebedde J, Borlaug BA, Kaye DM, Hasenfubeta G, Kawash R, Hoendermis E, Hummel SL, Cikes M, Gustafsson F, Chung ES, Mohan RC, Sverdlov AL, Swarup V, Winkler S, Hayward CS, Bergmann MW, Bugger H, McKenzie S, Nair A, Rieth A, Burkhoff D, Cutlip DE, Solomon SD, van Veldhuisen DJ, Leon MB, Shah SJ. Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials. Am Heart J. 2024 Dec;278:106-116. doi: 10.1016/j.ahj.2024.08.014. Epub 2024 Sep 3.

  PMID: 39237070 DERIVED

• Gustafsson F, Petrie MC, Komtebedde J, Swarup V, Winkler S, Hasenfuss G, Borlaug BA, Mohan RC, Flaherty JD, Sverdlov AL, Fail PS, Chung ES, Lurz P, Lilly S, Kaye DM, Cleland JGF, Cikes M, Leon MB, Cutlip DE, van Veldhuisen DJ, Solomon SD, Shah SJ. 2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II. JACC Heart Fail. 2024 Aug;12(8):1425-1438. doi: 10.1016/j.jchf.2024.04.011. Epub 2024 Jun 26.

  PMID: 38934964 DERIVED

• Patel RB, Silvestry FE, Komtebedde J, Solomon SD, Hasenfuss G, Litwin SE, Borlaug BA, Price MJ, Kawash R, Hummel SL, Cutlip DE, Leon MB, van Veldhuisen DJ, Rieth AJ, McKenzie S, Bugger H, Mazurek JA, Kapadia SR, Vanderheyden M, Ky B, Shah SJ. Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction: The REDUCE LAP-HF II Randomized Clinical Trial. JAMA Cardiol. 2024 Jun 1;9(6):507-522. doi: 10.1001/jamacardio.2024.0520.

  PMID: 38630494 DERIVED

• Patel RB, Reddy VY, Komtebedde J, Wegerich SW, Sekaric J, Swarup V, Walton A, Laurent G, Chetcuti S, Rademann M, Bergmann M, McKenzie S, Bugger H, Bruno RR, Herrmann HC, Nair A, Gupta DK, Lim S, Kapadia S, Gordon R, Vanderheyden M, Noel T, Bailey S, Gertz ZM, Trochu JN, Cutlip DE, Leon MB, Solomon SD, van Veldhuisen DJ, Auricchio A, Shah SJ. Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2023 Oct;11(10):1351-1362. doi: 10.1016/j.jchf.2023.05.024. Epub 2023 Jul 19.

  PMID: 37480877 DERIVED

• Litwin SE, Komtebedde J, Hu M, Burkhoff D, Hasenfuss G, Borlaug BA, Solomon SD, Zile MR, Mohan RC, Khawash R, Sverdlov AL, Fail P, Chung ES, Kaye DM, Blair J, Eicher JC, Hummel SL, Zirlik A, Westenfeld R, Hayward C, Gorter TM, Demers C, Shetty R, Lewis G, Starling RC, Patel S, Gupta DK, Morsli H, Penicka M, Cikes M, Gustafsson F, Silvestry FE, Rowin EJ, Cutlip DE, Leon MB, Kitzman DW, Kleber FX, Shah SJ; REDUCE LAP-HF Investigators and Research Staff. Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2023 Aug;11(8 Pt 2):1103-1117. doi: 10.1016/j.jchf.2023.01.030. Epub 2023 Mar 20.

  PMID: 36939661 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Heart Failure

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

• Marty 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: March 14, 2017
• First Posted: March 23, 2017
• Study Start: June 1, 2017
• Primary Completion: July 29, 2021
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 22, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); IT (1); FR (6); DK (1); JP (9); AU (6); DE (11); ES (1); CR (1); NL (4); US (44); PL (1); CA (1); GB (2)