Clinical trial NCT05425459: RESPONDER-HF Trial
Official title: Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction (EF) Heart Failure (Protocol #2201)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Heart Failure, Diastolic
Keywords: Heart failure with preserved ejection fraction (HFpEF)
Heart failure with midrange ejection fraction (HFmrEF)
Interatrial Shunt
Lead sponsor: Corvia Medical
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 750
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, Sham Controlled, Double Blinded Clinical Trial, with; 1:1 randomization

Detailed description: Following supine bicycle exercise hemodynamic assessment to verify eligibility, patients are sedated then randomized to the treatment or control group. Patients in both arms will undergo placement of femoral venous access sheath.

Patients randomized to the treatment arm will undergo a fluoroscopically and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and Corvia Atrial Shunt 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: Inclusion Criteria:

1. Chronic symptomatic heart failure (HF) documented by the following:

   1. Symptoms of HF requiring current treatment with diuretics if tolerated for ≥ 30 days AND
   2. New York Heart Association (NYHA) class II; OR NYHA class III, or ambulatory NYHA class IV symptoms; AND
   3. ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV) diuretics; or intensification of oral diuresis within the 12 months prior to study entry; OR an NT-proB-type Natriuretic Peptide (NT-pro BNP) value \> 150 pg/ml in normal sinus rhythm, \> 450 pg/ml in atrial fibrillation, or a brain natriuretic peptide (BNP) value \> 50 pg/ml in normal sinus rhythm, \> 150 pg/ml in atrial fibrillation within the past 6 months
2. Ongoing stable guideline-directed medical therapy (GDMT) HF management and management of comorbidities according to the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Heart Failure. Stable management includes a minimum period of 4 weeks post-hospitalization for any cause, including treatment with IV diuretics
3. Site determined echocardiographic LV ejection fraction ≥ 40% within the past 6 months, without documented ejection fraction \< 30% in the 5 years prior.
4. Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following:

   1. Left Atrial (LA) diameter \> 4 cm; or
   2. Diastolic LA volume \> 50 or LA volume index \> 28 ml/m2 or
   3. Lateral e' \< 10 cm/s; or
   4. e' \< 8 cm/s; or
5. Site determined elevated pulmonary capillary wedge pressure (PCWP) with a gradient compared to right atrial pressure (RAP) documented by end-expiratory PCWP during supine ergometer exercise ≥ 25 millimeters of mercury (mm Hg), and greater than RAP by ≥ 5 mm Hg.
6. Resting RAP ≤ 14 mmHg
7. Site determined hemodynamic evidence of peak exercise pulmonary vascular resistance (PVR) \< 1.75 Wood units
8. Age ≥ 40 years old
9. Participant has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the Institutional Review Board (IRB) or Ethics Committee (EC)
10. Participant is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams
11. Transseptal catheterization and femoral vein access to the right atrium is determined to be feasible by site interventional cardiology investigator.

Exclusion Criteria:

1. Advanced heart failure defined as one or more of the below:

   1. ACC/AHA/European Society of Cardiology (ESC) Stage D heart failure, non-ambulatory NYHA Class IV HF
   2. Cardiac index \< 2.0 L/min/m2
   3. Inotropic infusion (continuous or intermittent) for EF \< 40% within the past 6 months
   4. Patient is on the cardiac transplant waiting list.
2. Inability to perform 6-minute walk test (distance \< 50 meters), OR 6-minute walk test \> 600m
3. The patient has verified that the ability to walk 6 minutes is limited primarily by joint, foot, leg, hip or back pain; unsteadiness or dizziness or lifestyle (and not by shortness of breath and/or fatigue and/or chest pain)
4. Right ventricular dysfunction, assessed by the site cardiologist and defined as one or more of the following:

   1. More than mild right ventricular (RV) dysfunction as estimated by transthoracic echocardiogram (TTE); OR
   2. TAPSE \< 1.4 cm; OR
   3. Right ventricular (RV) size ≥ left ventricular (LV) size as estimated by TTE; OR
   4. Ultrasound or clinical evidence of congestive hepatopathy; OR
   5. Evidence of RV dysfunction defined by TTE as an RV fractional area change \< 35%.
5. Any implanted cardiac rhythm device
6. Structural heart repair aortic valve replacement (AVR) or mitral valve replacement (MVR) (surgical or percutaneous) within the past 12 months; planned valve intervention in the next 3 months, or presence of hemodynamically significant valve disease as assessed by the site cardiologist and defined as:

   1. Mitral valve disease grade ≥ 3+ mitral regurgitation (MR) or \> mild Mitral Stenosis (MS); OR
   2. Tricuspid valve (TR) regurgitation grade ≥ 2+ TR; OR
   3. Aortic valve disease ≥ 2+ aortic regurgitation (AR) or \> moderate aortic stenosis (AS)
7. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation
8. Participants with existing or surgically closed (with a patch) atrial septal defects. Participants with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are not excluded
9. Myocardial Infarction (MI) and/or percutaneous cardiac intervention within past 3 months; Coronary Artery Bypass Graft (CABG) surgery in past 3 months or any planned cardiac interventions in the 3 months following enrollment.
10. Known clinically significant un-revascularized coronary artery disease, defined as: coronary artery stenosis with angina or other evidence of ongoing active coronary ischemia
11. Known clinically significant untreated carotid artery stenosis likely to require intervention
12. Atrial fibrillation with resting heart rate (HR) \> 100 beats-per-minute (BPM)
13. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis)
14. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
15. Participant is contraindicated to receive either dual antiplatelet therapy, or an oral anticoagulant; or has a documented coagulopathy
16. Anemia with Hemoglobin \< 10 g/dl
17. Chronic pulmonary disease requiring continuous home oxygen, OR significant chronic pulmonary disease defined as forced expiratory volume (FEV)1 \<1Liter
18. Resting arterial oxygen saturation \< 95% on room air, \<93% when residing at high altitude
19. Currently requiring dialysis; or estimated glomerular filtration rate eGFR \< 25ml/min/1.73 m2 by chronic kidney disease (CKD) CKD-Epi equation
20. Systolic blood pressure \> 170 mm Hg at screening
21. Significant hepatic impairment defined as 3 times upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
22. Participants on significant immunosuppressive treatment or on systemic steroid treatment
23. Life expectancy less than 12 months for known non-cardiovascular reasons
24. Known hypersensitivity to nickel or titanium
25. Women of childbearing potential
26. Severe obstructive sleep apnea not treated with continuous positive airway pressure (CPAP) or other measures
27. Body Mass Index (BMI) \> 45; BMI 40 - 45 is also excluded unless in the opinion of the investigator, vascular access can be obtained safely
28. Severe depression and/or anxiety
29. Currently participating in an investigational drug or device study that would interfere with the conduct or results of this study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational
30. In the opinion of the investigator, the Participant is not an appropriate candidate for the study.

Primary outcomes:
measure: Composite Primary Endpoint
timeFrame: Up to 12 months
Secondary outcomes:
measure: The incidence of cardiovascular mortality
timeFrame: Up to 12 months
measure: The rate of time-to-cardiovascular mortality
timeFrame: Up to 12 months
measure: The rate of major adverse cardiac periprocedural events
timeFrame: Through 30 days
measure: The incidence of non-fatal, ischemic stroke
timeFrame: Through 12 months
measure: The rate of new onset or worsening of kidney dysfunction
timeFrame: Through 12 months
measure: The incidence of thrombo-embolic complications including transient ischaemic attack (TIA) and systemic embolization)
timeFrame: Through 12 months
measure: The incidence of newly acquired persistent or permanent atrial fibrillation (AF) or atrial flutter
timeFrame: Through 12 months
measure: The incidence of participants with a ≥30% decrease in Tricuspid Annular Plane Systolic Excursion (TAPSE)
timeFrame: Through 12 months
measure: The rate of heart failure (HF) admissions
timeFrame: Through 24 months
measure: The change in New York Heart Association (NYHA) Class
timeFrame: 12 months
measure: The change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
timeFrame: 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Long Beach
country: United States
facility: MemorialCare Long Beach Medical Center
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Naples
country: United States
facility: NCH Naples
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Lawrenceville
country: United States
facility: Northside Hospital Gwinnett Campus
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Glenview
country: United States
facility: Endeavor Health-Northshore
state: Illinois
city: Shreveport
country: United States
facility: LSU Health Shreveport
state: Louisiana
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Hospital University Campus
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell
state: New York
city: Cincinnati
country: United States
facility: Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinatti Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic OH
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner medical Center
state: Ohio
city: Tulsa
country: United States
facility: St. Francis Hospital (Heart Hospital)
state: Oklahoma
city: Portland
country: United States
facility: OHSU Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Cardiovascular Institute (CVI) Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: North Central Heart-Avera
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Morgantown
country: United States
facility: West Virginia Heart and Vascular
state: West Virginia
city: Darlinghurst
country: Australia
facility: St. Vincents Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Chermside
country: Australia
facility: Prince Charles Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Graz
country: Austria
facility: LKH University Clinic
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwziekenhuis Aalst (OLV)
city: Vancouver
country: Canada
facility: St. Paul's Hospital Providence Health Care
state: British Columbia
city: Toronto
country: Canada
facility: Unity Health Toronto St. Michael's Hospital
state: Ontario
city: Bad Krozingen
country: Germany
facility: University Heart Center Bad Krozingen
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik
city: Berlin
country: Germany
facility: Hospital Charité - University Medicine Berlin
city: Berlin
country: Germany
facility: Vivantes Clinic Friedrichshain Berlin
city: Berlin
country: Germany
facility: DRK Clinics Berlin Koepenick
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Dresden
country: Germany
facility: Heart Center of Dresden
city: Duesseldorf
country: Germany
facility: UK Duesseldorf
city: Freiburg
country: Germany
facility: University Heart Center Freiburg
city: Göttingen
country: Germany
facility: Georg-August Universität Gottingen Universitätsklinikum Göttingen Klinik für Kardiologie und Pneumologie
city: Hamburg
country: Germany
facility: Marienkrankenhaus Hospital Hamburg
city: Hamburg
country: Germany
facility: Asklepios Clinic Altona Hamburg
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig - Universitätsklinik
city: Luebeck
country: Germany
facility: University Hospital Schleswig-Holstein (UKSH) Luebeck
city: Münster
country: Germany
facility: University Hospital Münster
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin
city: Ulm
country: Germany
facility: Ulm University Hospital
city: Würzburg
country: Germany
facility: University Hospital Wurzburg
city: Groningen
country: Netherlands
facility: UMCG - Groningen
Study officials:
affiliation: Northwestern Memorial Hospital
name: Sanjiv Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Martin Leon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Borlaug BA, Blair J, Bergmann MW, Bugger H, Burkhoff D, Bruch L, Celermajer DS, Claggett B, Cleland JGF, Cutlip DE, Dauber I, Eicher JC, Gao Q, Gorter TM, Gustafsson F, Hayward C, van der Heyden J, Hasenfuss G, Hummel SL, Kaye DM, Komtebedde J, Massaro JM, Mazurek JA, McKenzie S, Mehta SR, Petrie MC, Post MC, Nair A, Rieth A, Silvestry FE, Solomon SD, Trochu JN, Van Veldhuisen DJ, Westenfeld R, Leon MB, Shah SJ; REDUCE LAP-HF-II Investigators. Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure. Circulation. 2022 May 24;145(21):1592-1604. doi: 10.1161/CIRCULATIONAHA.122.059486. Epub 2022 Mar 31.
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.