RESPONDER-HF Trial

February 5, 2024 updated by: Corvia Medical

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

750

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia
        • Recruiting
        • St. Vincents Hospital
        • Contact:
        • Principal Investigator:
          • Christopher Hayward, MD
      • New Lambton Heights, New South Wales, Australia, 2305
    • Queensland
      • Chermside, Queensland, Australia, 4032
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • The Alfred Hospital
        • Contact:
        • Principal Investigator:
          • David Kaye, MD
  • Austria
      • Graz, Austria, 8047
  • Belgium
      • Aalst, Belgium, B-9300
        • Recruiting
        • Onze-Lieve-Vrouwziekenhuis Aalst (OLV)
        • Contact:
        • Principal Investigator:
          • Martin Penicka, MD
  • Germany
      • Bad Nauheim, Germany
        • Recruiting
        • Kerckhoff Klinik
        • Principal Investigator:
          • Andreas Rieth, MD
      • Berlin, Germany
        • Recruiting
        • Unfallkrankenhaus Berlin
        • Principal Investigator:
          • Sebastian Winkler, MD
      • Duesseldorf, Germany
        • Recruiting
        • UK Duesseldorf
        • Principal Investigator:
          • Amin Polzin, MD
      • Freiburg, Germany
        • Recruiting
        • University Heart Center Freiburg
        • Principal Investigator:
          • Sebastian Grundmann, MD
      • Göttingen, Germany
        • Recruiting
        • Georg-August Universität Gottingen Universitätsklinikum Göttingen Klinik für Kardiologie und Pneumologie
        • Principal Investigator:
          • Gerd Hasenfuss, MD
  • Netherlands
      • Groningen, Netherlands
        • Recruiting
        • UMCG - Groningen
        • Principal Investigator:
          • Elke Hoendermis, MD
      • Maastricht, Netherlands
        • Recruiting
        • Maastricht University Medical Center
        • Contact:
        • Principal Investigator:
          • Arantxa Barandiarian, MD
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Arizona Cardiovascular Research Center
        • Contact:
          • Vijendra Swarup, MD
    • California
      • La Jolla, California, United States, 92037
        • Not yet recruiting
        • Scripps Clinic
        • Principal Investigator:
          • Rajeev Mohan, MD
    • Florida
      • Naples, Florida, United States, 34102
        • Recruiting
        • NCH Naples
        • Contact:
        • Principal Investigator:
          • Viviana Navas, MD
      • Sarasota, Florida, United States, 34239
        • Recruiting
        • Sarasota Memorial Hospital (Intercoastal Medical Group)
        • Contact:
        • Principal Investigator:
          • Hakim Morsli, MD
      • Weston, Florida, United States, 33331
        • Recruiting
        • Cleveland Clinic Florida
        • Contact:
        • Principal Investigator:
          • David Baran, MD
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
        • Principal Investigator:
          • John Blair, MD
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
          • Daniel Roshevsky
        • Principal Investigator:
          • James Flaherty, MD
        • Contact:
    • Louisiana
      • Houma, Louisiana, United States, 70360
        • Recruiting
        • Cardiovascular Institute of the South (CIS)
        • Contact:
        • Principal Investigator:
          • Peter Fail, MD
        • Contact:
          • Benoit
      • Shreveport, Louisiana, United States, 71103
        • Recruiting
        • LSU Health Shreveport
        • Contact:
        • Principal Investigator:
          • Steve Bailey, MD
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Recruiting
        • Lahey Hospital & Medical Center
        • Contact:
        • Principal Investigator:
          • Gautam Gadey, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Health Systems
        • Principal Investigator:
          • Scott Hummel, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Principal Investigator:
          • Barry Borlaug, MD
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell
        • Contact:
        • Principal Investigator:
          • Parag Goyal, MD
    • Ohio
      • Cincinnati, Ohio, United States, 45219
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic OH
        • Contact:
        • Principal Investigator:
          • Sanjeeb Bhattacharya, MD
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Wexner Medical Center
        • Principal Investigator:
          • Scott Lilly, MD
        • Contact:
          • Annie Kellum
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Recruiting
        • St. Francis Hospital (Heart Hospital)
        • Contact:
        • Principal Investigator:
          • Doug Ensley, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • South Carolina
      • Charleston, South Carolina, United States, 29403
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • James Flaherty, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37235
        • Recruiting
        • Vanderbilt University
        • Contact:
        • Principal Investigator:
          • Deepak Gupta, MD
    • Texas
      • Austin, Texas, United States, 78701
        • Recruiting
        • Ascension Seton Medical Center
        • Principal Investigator:
          • Mark Gajjar, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor St. Luke's Medical Center
        • Contact:
        • Principal Investigator:
          • Ajit Nair, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Mohammad Abuannadi, MD
        • Contact:
    • West Virginia
      • Morgantown, West Virginia, United States, 26508
        • Not yet recruiting
        • West Virginia Heart and Vascular
        • Principal Investigator:
          • Vikrant Jagadeesan, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Participants randomized to the treatment arm will undergo a fluoroscopic and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and InterAtrial Shunt Device (IASD) System II implant procedure.
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.
Sham Comparator: Control
Participants randomized to the control arm will undergo fluoroscopy and intracardiac echocardiography from the femoral vein or transesophageal echocardiography, for examination of the atrial septum and left atrial appendage.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Primary Endpoint
Time Frame: Up to 12 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of cardiovascular mortality
Time Frame: Up to 12 months
The incidence of cardiovascular mortality through 12 months.
Up to 12 months
The rate of time-to-cardiovascular mortality
Time Frame: Up to 12 months
Time-to-cardiovascular mortality through 12 months.
Up to 12 months
The rate of major adverse cardiac periprocedural events
Time Frame: Through 30 days

Major adverse cardiac periprocedural events through 30 days defined as:

  1. Cardiac death
  2. Myocardial infarction
  3. Cardiac tamponade
  4. Emergency cardiac surgery.
Through 30 days
The incidence of non-fatal, ischemic stroke
Time Frame: Through 12 months
Incidence of non-fatal, ischemic stroke
Through 12 months
The rate of new onset or worsening of kidney dysfunction
Time Frame: Through 12 months
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
The incidence of thrombo-embolic complications including transient ischaemic attack (TIA) and systemic embolization)
Time Frame: Through 12 months
The incidence of thrombo-embolic complications (TIA and systemic embolization) through 12 months
Through 12 months
The incidence of newly acquired persistent or permanent atrial fibrillation (AF) or atrial flutter
Time Frame: Through 12 months
The incidence of newly acquired persistent or permanent AF or atrial flutter
Through 12 months
The incidence of participants with a ≥30% decrease in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time Frame: Through 12 months
The incidence of participants with a ≥30% decrease Tricuspid Annular Plane Systolic Excursion (TAPSE)
Through 12 months
The rate of heart failure (HF) admissions
Time Frame: Through 24 months
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
The change in New York Heart Association (NYHA) Class
Time Frame: 12 months
Change in NYHA functional Class between baseline and 12 months
12 months
The change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
Time Frame: 12 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Corvia Medical

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2022

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

March 1, 2031

Study Registration Dates

First Submitted

June 13, 2022

First Submitted That Met QC Criteria

June 16, 2022

First Posted (Actual)

June 21, 2022

Study Record Updates

Last Update Posted (Estimated)

February 6, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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