Clinical trial NCT03088033: REDUCE LAP-HF TRIAL II
Official title: A Study to Evaluate the Corvia Medical, Inc. IASD® System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure
Lead sponsor: Corvia Medical
Sponsor class: INDUSTRY
First posted: 2017-03-23
Enrollment: 608
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite Primary Endpoint
timeFrame: Up to 24 months
Secondary outcomes:
measure: Composite safety endpoint defined as follows:
timeFrame: 12 months
measure: Rate of heart failure admissions
timeFrame: Up to 24 months
measure: Change in NYHA Class
timeFrame: 12 months
measure: Change in Kansas City Cardiomyopathy Questionnaire
timeFrame: 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: La Jolla
country: United States
facility: Kaiser Permanente San Diego
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco Medical Center
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute, Inc.
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Northshore Healthcare
state: Illinois
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Tufts New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Heart and Vascular
state: Missouri
city: Hamilton
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest
state: North Carolina
city: Cincinnati
country: United States
facility: Christ Hospital Ohio Heart and Vascular Institute
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University College of Medicine
state: Ohio
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center, Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Camperdown
country: Australia
facility: Concord Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Aalst
country: Belgium
facility: OLVZ Aalst
city: Brugge
country: Belgium
facility: Az Sint-Jan Brugge
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Zagreb
country: Croatia
facility: University Hospital Center, Zagreb
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Dijon
country: France
facility: CHU de Dijon
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital La Pitié Salpétrière
city: Rennes
country: France
facility: CHU de Rennes
city: Rouen
country: France
facility: CHU de Rouen
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin
city: Dusseldorf
country: Germany
facility: Universitatklinikum Duseldorf
city: Freiburg
country: Germany
facility: Heart Center Freiburg University
city: Gottingen
country: Germany
facility: Georg-August-Universitat
city: Hamburg
country: Germany
facility: Cardiologicum CRC
city: Hamburg
country: Germany
facility: UKE Hamburg
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Leipzig
country: Germany
facility: Heart Center of the University of Leipzig
city: Munich
country: Germany
facility: Klinikum der Universität Munchen
city: Milano
country: Italy
facility: University of Milano
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hyōgo
country: Japan
facility: The Hospital of Hyogo College of Medicine
city: Nara
country: Japan
facility: Nara Medical University Hospital
city: Osaka
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
city: Tottori
country: Japan
facility: Tottori University Hospital
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Maastricht
country: Netherlands
facility: Maastricht UMC Hart & Vaat Centrum
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis
city: Wroclaw
country: Poland
facility: Fourth Military Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Glasgow
country: United Kingdom
facility: Golden Jubilee Hospital
city: London
country: United Kingdom
facility: Guys & St Thomas NHS Foundation Trust
Study officials:
affiliation: Northwestern Memorial Hospital
name: Sanjiv Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Marty Leon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.