REDUCE LAP-HF TRIAL II

Sponsor

Corvia Medical (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03088033

Collaborator

(none)

608

Enrollment

Locations

Arms

111

Anticipated Duration (Months)

6.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: IASD System II implant Other: intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

608 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2017

Actual Primary Completion Date :

Jul 29, 2021

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

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.

Arm

Intervention/Treatment

Experimental: Treatment

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.

Outcome Measures

Primary Outcome Measures

Composite Primary Endpoint [Up to 24 months]
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.

Secondary Outcome Measures

Composite safety endpoint defined as follows: [12 months]
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
Rate of heart failure admissions [Up to 24 months]
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
Change in NYHA Class [12 months]
Change in NYHA functional Class assessed by a blinded physician between baseline and 12 months
Change in Kansas City Cardiomyopathy Questionnaire [12 months]
Change in KCCQ score between baseline and 12 months, categorized as ≤0, >0 - 5, >5 - 10, >10 - 15, >15 - 20, >20 - 25, >25.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cardiovascular Research Center	Phoenix	Arizona	United States	85016
2	University of Arizona College of Medicine	Tucson	Arizona	United States	85724
3	Scripps Clinic	La Jolla	California	United States	92037
4	Kaiser Permanente San Diego	La Jolla	California	United States	92120
5	Kaiser Permanente San Francisco Medical Center	San Francisco	California	United States	94115
6	South Denver Cardiology Associates	Littleton	Colorado	United States	80120
7	Yale University	New Haven	Connecticut	United States	06510
8	Medstar Washington Hospital Center	Washington	District of Columbia	United States	20010
9	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33307
10	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
11	Tallahassee Research Institute, Inc.	Tallahassee	Florida	United States	33208
12	Cleveland Clinic Florida	Weston	Florida	United States	33331
13	Northwestern University	Chicago	Illinois	United States	60611
14	University of Chicago Medical Center	Chicago	Illinois	United States	60637
15	Evanston Northshore Healthcare	Evanston	Illinois	United States	60201
16	Cardiovascular Institute of the South	Houma	Louisiana	United States	70360
17	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
18	Tufts New England Medical Center	Boston	Massachusetts	United States	02111
19	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
20	University of Michigan Health System	Ann Arbor	Michigan	United States	41809
21	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States	55407
22	Mayo Clinic	Rochester	Minnesota	United States	55905
23	St. Louis Heart and Vascular	Saint Louis	Missouri	United States	63136
24	Hackensack University Medical Center	Hamilton	New Jersey	United States	08690
25	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
26	Vassar Brothers Medical Center	Poughkeepsie	New York	United States	12601
27	Duke University Medical Center	Durham	North Carolina	United States	27710
28	Wake Forest	Winston-Salem	North Carolina	United States	27157
29	Christ Hospital Ohio Heart and Vascular Institute	Cincinnati	Ohio	United States	45219
30	Cleveland Clinic	Cleveland	Ohio	United States	44195
31	Ohio State University College of Medicine	Columbus	Ohio	United States	43210
32	Ohio Health	Columbus	Ohio	United States	43214
33	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
34	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
35	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
36	Medical University of South Carolina	Charleston	South Carolina	United States	29425
37	Vanderbilt University	Nashville	Tennessee	United States	37242
38	Baylor University Medical Center, Dallas	Dallas	Texas	United States	75246
39	Baylor College of Medicine	Houston	Texas	United States	77030
40	Houston Methodist Hospital	Houston	Texas	United States	77030
41	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284
42	Intermountain Medical Center	Murray	Utah	United States	84157
43	University of Utah Medical Center	Salt Lake City	Utah	United States	84132
44	University of Virginia	Charlottesville	Virginia	United States	22908
45	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23298
46	Concord Hospital	Camperdown	New South Wales	Australia	2050
47	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
48	John Hunter Hospital	Newcastle	New South Wales	Australia	2305
49	St. Vincent Hospital	Sydney	New South Wales	Australia	2010
50	The Prince Charles Hospital	Brisbane	Queensland	Australia	4032
51	The Alfred Hospital	Melbourne	Victoria	Australia	3004
52	Medizinische Universität Graz	Graz		Austria
53	OLVZ Aalst	Aalst		Belgium
54	Az Sint-Jan Brugge	Brugge		Belgium
55	Hamilton Health Sciences	Hamilton	Ontario	Canada
56	University Hospital Center, Zagreb	Zagreb		Croatia
57	Rigshospitalet	Copenhagen		Denmark
58	CHU de Dijon	Dijon		France
59	CHU de Nantes	Nantes		France
60	Hôpital Bichat	Paris		France
61	Hôpital La Pitié Salpétrière	Paris		France
62	CHU de Rennes	Rennes		France
63	CHU de Rouen	Rouen		France
64	Kerckhoff Klinik	Bad Nauheim		Germany
65	Charite Universitatsmedizin Berlin	Berlin		Germany
66	Unfallkrankenhaus Berlin	Berlin		Germany
67	Universitatklinikum Duseldorf	Dusseldorf		Germany
68	Heart Center Freiburg University	Freiburg		Germany
69	Georg-August-Universitat	Gottingen		Germany
70	Cardiologicum CRC	Hamburg		Germany
71	UKE Hamburg	Hamburg		Germany
72	University of Heidelberg	Heidelberg		Germany
73	Heart Center of the University of Leipzig	Leipzig		Germany
74	Klinikum der Universität Munchen	Munich		Germany
75	University of Milano	Milano		Italy
76	Hokkaido University Hospital	Sapporo	Hokkaido	Japan
77	Kyushu University Hospital	Fukuoka		Japan
78	The Hospital of Hyogo College of Medicine	Hyōgo		Japan
79	Nara Medical University Hospital	Nara		Japan
80	National Cerebral and Cardiovascular Center	Osaka		Japan
81	Osaka University Hospital	Osaka		Japan
82	The University of Tokyo Hospital	Tokyo		Japan
83	Tottori University Hospital	Tottori		Japan
84	Toyama University Hospital	Toyama		Japan
85	VU University Medical Center	Amsterdam		Netherlands
86	UMC Groningen	Groningen		Netherlands
87	Maastricht UMC Hart & Vaat Centrum	Maastricht		Netherlands
88	St Antonius Ziekenhuis	Nieuwegein		Netherlands
89	Fourth Military Hospital	Wroclaw		Poland
90	Hospital Clinic Barcelona	Barcelona		Spain
91	Golden Jubilee Hospital	Glasgow		United Kingdom
92	Guys & St Thomas NHS Foundation Trust	London		United Kingdom

Sponsors and Collaborators

Corvia Medical

Investigators

Principal Investigator: Sanjiv Shah, MD, Northwestern Memorial Hospital
Principal Investigator: Marty Leon, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Corvia Medical

ClinicalTrials.gov Identifier:

NCT03088033

Other Study ID Numbers:

1601

First Posted:

Mar 23, 2017

Last Update Posted:

Jun 21, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Additional relevant MeSH terms:

Heart Failure

Study Results

No Results Posted as of Jun 21, 2022