REDUCE LAP-HF TRIAL II

A Study to Evaluate the Corvia Medical, Inc. IASD® System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure

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

Study Overview

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

Detailed Description

Following supine bicycle exercise testing to assess eligibility, the eligible patients are randomized to the treatment or control group.

All patients will be sedated, and both treatment and control arm patients will undergo placement of a femoral venous access sheath after randomization.

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. 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 (Anticipated): 608
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Concord Hospital
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Austria
  • Graz, Austria
    • Medizinische Universitat Graz
• Belgium
  • Aalst, Belgium
    • OLVZ Aalst
  • Brugge, Belgium
    • AZ Sint-Jan Brugge
• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences
• Croatia
  • Zagreb, Croatia
    • University Hospital Center, Zagreb
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• France
  • Dijon, France
    • CHU de DIJON
  • Nantes, France
    • CHU de Nantes
  • Paris, France
    • Hôpital Bichat
  • Paris, France
    • Hôpital La Pitié Salpêtrière
  • Rennes, France
    • CHU de Rennes
  • Rouen, France
    • CHU de ROUEN
• Germany
  • Bad Nauheim, Germany
    • Kerckhoff Klinik
  • Berlin, Germany
    • Charité Universitätsmedizin Berlin
  • Berlin, Germany
    • Unfallkrankenhaus Berlin
  • Dusseldorf, Germany
    • Universitatklinikum Duseldorf
  • Freiburg, Germany
    • Heart Center Freiburg University
  • Gottingen, Germany
    • Georg-August-Universität
  • Hamburg, Germany
    • UKE Hamburg
  • Hamburg, Germany
    • Cardiologicum CRC
  • Heidelberg, Germany
    • University of Heidelberg
  • Leipzig, Germany
    • Heart Center of the University of Leipzig
  • Munich, Germany
    • Klinikum der Universität München
• Italy
  • Milano, Italy
    • University of Milano
• Japan
  • Fukuoka, Japan
    • Kyushu University Hospital
  • Hyōgo, Japan
    • The Hospital of Hyogo College of Medicine
  • Nara, Japan
    • Nara Medical University Hospital
  • Osaka, Japan
    • Osaka University Hospital
  • Osaka, Japan
    • National Cerebral and Cardiovascular Center
  • Tokyo, Japan
    • The University of Tokyo Hospital
  • Tottori, Japan
    • Tottori University Hospital
  • Toyama, Japan
    • Toyama University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Hokkaido University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • VU University Medical Center
  • Groningen, Netherlands
    • UMC Groningen
  • Maastricht, Netherlands
    • Maastricht UMC Hart & Vaat Centrum
  • Nieuwegein, Netherlands
    • St Antonius Ziekenhuis
• Poland
  • Wroclaw, Poland
    • Fourth Military Hospital
• Spain
  • Barcelona, Spain
    • Hospital Clinic Barcelona
• United Kingdom
  • Glasgow, United Kingdom
    • Golden Jubilee Hospital
  • London, United Kingdom
    • Guys & St Thomas NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Cardiovascular Research Center
    • Tucson, Arizona, United States, 85724
      • University of Arizona College of Medicine
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • La Jolla, California, United States, 92120
      • Kaiser Permanente San Diego
    • San Francisco, California, United States, 94115
      • Kaiser Permanente San Francisco Medical Center
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33307
      • Holy Cross Hospital
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Tallahassee, Florida, United States, 33208
      • Tallahassee Research Institute, Inc.
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Evanston, Illinois, United States, 60201
      • Evanston Northshore Healthcare
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Cardiovascular Institute of the South
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts New England Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 41809
      • University of Michigan Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63136
      • St. Louis Heart and Vascular
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Hackensack University Medical Center
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital Ohio Heart and Vascular Institute
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43214
      • Ohio Health
    • Columbus, Ohio, United States, 43210
      • Ohio State University College of Medicine
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37242
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center, Dallas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • San Antonio, Texas, United States, 78284
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

SELECT INCLUSION CRITERIA

• 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

SELECT EXCLUSION CRITERIA

• 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

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; 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; 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; 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); 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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite safety endpoint defined as follows:	Cardiovascular mortality; Non-fatal, ischemic stroke; New onset or worsening of kidney dysfunction (defined as eGFR decrease of > 20 ml/min); Major adverse cardiac events through 12-months defined as: i. Cardiac death; ii. Myocardial infarction; iii. Cardiac tamponade; iv. Emergency cardiac surgery; Thrombo-embolic complications (TIA, systemic embolization); Newly acquired persistent or permanent AF or atrial flutter through; ≥30% increase in RV size/decrease in TAPSE	12 months
Rate of heart failure admissions	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-month follow-up	Up to 24 months
Change in NYHA Class	Change in NYHA functional Class assessed by a blinded physician between baseline and 12 months	12 months
Change in Kansas City Cardiomyopathy Questionnaire	Change in KCCQ score between baseline and 12 months, categorized as ≤0, >0 - 5, >5 - 10, >10 - 15, >15 - 20, >20 - 25, >25.	12 months

Collaborators and Investigators

• Sponsor: Corvia Medical
• Investigators: Principal Investigator: Sanjiv Shah, MD, Northwestern Memorial Hospital

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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): July 29, 2021
• Study Completion (Anticipated): September 1, 2026

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 1601 (University Hospital Bern)

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