RESPONDER-HF Trial

Heart Failure Clinical 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05425459
• Other study ID #: 2201
• Status: Recruiting
• Phase: N/A
• Start date: November 17, 2022
• Est. completion date: March 2031

Study information

• Verified date: February 2024
• Source: Corvia Medical
• Contact: Jan Komtebedde, DVM
• Phone: 978-654-6113
• Email: jkomtebedde[@]corviamedical.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicenter, Prospective, Randomized, Sham Controlled, Double Blinded Clinical Trial, with; 1:1 randomization

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: March 2031
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Diastolic

Intervention

Device:
• Corvia Atrial Shunt System / IASD System II
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	Prince Charles Hospital	Chermside	Queensland
Australia	St. Vincents Hospital	Darlinghurst	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Austria	LKH University Clinic	Graz
Belgium	Onze-Lieve-Vrouwziekenhuis Aalst (OLV)	Aalst
Germany	Kerckhoff Klinik	Bad Nauheim
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	UK Duesseldorf	Duesseldorf
Germany	University Heart Center Freiburg	Freiburg
Germany	Georg-August Universität Gottingen Universitätsklinikum Göttingen Klinik für Kardiologie und Pneumologie	Göttingen
Netherlands	UMCG - Groningen	Groningen
Netherlands	Maastricht University Medical Center	Maastricht
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	Ascension Seton Medical Center	Austin	Texas
United States	Lahey Hospital & Medical Center	Burlington	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	Cincinnati	Ohio
United States	Cleveland Clinic OH	Cleveland	Ohio
United States	Ohio State University Wexner medical Center	Columbus	Ohio
United States	Cardiovascular Institute of the South (CIS)	Houma	Louisiana
United States	Baylor St. Luke's Medical Center	Houston	Texas
United States	Scripps Clinic	La Jolla	California
United States	West Virginia Heart and Vascular	Morgantown	West Virginia
United States	NCH Naples	Naples	Florida
United States	Vanderbilt University	Nashville	Tennessee
United States	Weill Cornell	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Cardiovascular Research Center	Phoenix	Arizona
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Sarasota Memorial Hospital (Intercoastal Medical Group)	Sarasota	Florida
United States	LSU Health Shreveport	Shreveport	Louisiana
United States	St. Francis Hospital (Heart Hospital)	Tulsa	Oklahoma
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Corvia Medical

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Germany,  Netherlands, 

References & Publications (2)

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. Erratum In: Circulation. 2022 Jul 26;146(4):e12. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Primary Endpoint	The primary endpoint is a composite of heart failure event rates and Kansas City Cardiomyopathy Questionnaire (KCCQ) at 12 months.; Responses are given on a Likert scale that for each individual item is scored on a scale of 0-100 with higher scores indicating better health.	Up to 12 months
Secondary	The incidence of cardiovascular mortality	The incidence of cardiovascular mortality through 12 months.	Up to 12 months
Secondary	The rate of time-to-cardiovascular mortality	Time-to-cardiovascular mortality through 12 months.	Up to 12 months
Secondary	The rate of major adverse cardiac periprocedural events	Major adverse cardiac periprocedural events through 30 days defined as: Cardiac death; Myocardial infarction; Cardiac tamponade; Emergency cardiac surgery.	Through 30 days
Secondary	The incidence of non-fatal, ischemic stroke	Incidence of non-fatal, ischemic stroke	Through 12 months
Secondary	The rate of new onset or worsening of kidney dysfunction	New onset or worsening of kidney dysfunction (defined as estimated glomerular filtration rate (eGFR) decrease of > 20 ml/min/1.73 m2) through 12 months	Through 12 months
Secondary	The incidence of thrombo-embolic complications including transient ischaemic attack (TIA) and systemic embolization)	The incidence of thrombo-embolic complications (TIA and systemic embolization) through 12 months	Through 12 months
Secondary	The incidence of newly acquired persistent or permanent atrial fibrillation (AF) or atrial flutter	The incidence of newly acquired persistent or permanent AF or atrial flutter	Through 12 months
Secondary	The incidence of participants with a =30% decrease in Tricuspid Annular Plane Systolic Excursion (TAPSE)	The incidence of participants with a =30% decrease Tricuspid Annular Plane Systolic Excursion (TAPSE)	Through 12 months
Secondary	The rate of heart failure (HF) admissions	Total rate (first plus recurrent) per patient year of heart failure (HF) admissions or healthcare facility visits for intravenous diuresis or urgent visits with intensification of oral diuresis for HF through 24 months, analyzed when the last randomized participant completes 12 months follow-up.	Through 24 months
Secondary	The change in New York Heart Association (NYHA) Class	Change in NYHA functional Class between baseline and 12 months	12 months
Secondary	The change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score between baseline and 12 months, categorized as proportion of patients with changes of =0, >0 - 5, >5 - 10, >10 - 15, >15 - 20, >20 - 25, >25 points. Responses are given on a Likert scale that for each individual item is scored on a scale of 0-100 with higher scores indicating better health	12 months