REDUCE LAP-HF TRIAL II

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03088033
• Other study ID #: 1601
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 1, 2017
• Est. completion date: September 2026

Study information

• Verified date: February 2023
• Source: Corvia Medical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 608
• Est. completion date: September 2026
• Est. primary completion date: July 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

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.

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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Corvia Medical

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Croatia,  Denmark,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Change in NYHA Class	Change in NYHA functional Class assessed by a blinded physician between baseline and 12 months	12 months
Secondary	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