Beating Heart Mitral Valve Repair With the HARPOON™ System (RESTORE)

A Prospective, Multi-center Trial to Evaluate the Safety and Effectiveness of Beating Heart Mitral Valve Repair With the HARPOON™ System (RESTORE)

The objective of the study is to evaluate the safety and effectiveness of the HARPOON™ System in the treatment of patients with severe degenerative mitral regurgitation (DMR).

Study Overview

• Status: Active, not recruiting
• Conditions: Mitral Regurgitation
• Intervention / Treatment: Device: HARPOON™ Beating Heart Mitral Valve Repair System

Detailed Description

RESTORE is a prospective, multicenter, non-randomized trial designed to evaluate the safety and effectiveness of the HARPOON™ Beating Heart Mitral Valve Repair System in patients with severe degenerative mitral regurgitation (DMR).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94118
      • UCSF
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cardiovascular Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Each subject is required to meet all of the following inclusion criteria:

1. Patient is >/= 21 years old.
2. Presence of severe degenerative mitral regurgitation with mid-segment posterior leaflet prolapse (without commissural involvement) by echocardiographic study.
3. Mitral leaflet coaptation surface sufficient to reduce mitral regurgitation without undue leaflet tension, based on the judgment of the Echocardiographic Core Lab.
4. Patient competent to sign informed consent and able to return for follow-up and is capable of participating in all testing associated with this clinical investigation.

Exclusion Criteria:

Patients will be excluded if ANY of the following criteria apply:

1. Functional mitral regurgitation (FMR).
2. Evidence of anterior or bileaflet prolapse.
3. Severe mitral annular calcification (MAC).
4. Moderate or greater leaflet calcification.
5. Fragile or thinning apex (e.g. LV aneurysm).
6. Have undergone cardiac or peripheral vascular procedures within 30 days prior to the trial procedure.
7. Planned cardiac or peripheral vascular procedures within 30 days after the trial procedure.
8. Requirement for concomitant cardiac surgery.
9. Severe pulmonary hypertension (pulmonary artery systolic pressure > 60mmHg).
10. Severe aortic stenosis or insufficiency.
11. Severe tricuspid regurgitation. (Patients with mild or moderate tricuspid regurgitation are not excluded.)
12. Left ventricular ejection fraction (LVEF) <30%, or severely impaired right ventricular dysfunction as measured by the core lab.
13. Any history of endocarditis.
14. Contraindication to cardiac surgery, including hostile chest or history of mediastinal radiation.
15. Previous structural heart intervention (e.g. any heart valve replacement or repair procedures). Previous percutaneous coronary intervention (PCI) is allowed.
16. Previous coronary artery bypass grafting (CABG).
17. Stroke within 30 days prior to index procedure.
18. ST segment elevation myocardial infarction (STEMI) requiring intervention within 30 days prior to index procedure.
19. Evidence of cirrhosis or hepatic synthetic failure (Child-Pugh Class B or higher, [or MELD score of ≥ 13]).
20. Renal insufficiency CKD Stage 3b or worse (GFR < 45 ml/min/1.73 m2).
21. Hemodynamic instability or cardiogenic shock at the time of enrollment (e.g. requiring inotropic support or mechanical support devices).
22. History of bleeding diathesis or coagulopathy or leukopenia (WBC < 3000 mcL) or acute anemia (Hb < 9 g/dL) or thrombocytopenia (platelets < 50,000 cells mcL).
23. Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments (as assessed by Case Review Committee).
24. Refuse blood products.
25. Planned treatment with any other investigational device or procedure through 1-year follow-up, or who are currently participating in an investigational drug or device trial.
26. Carotid stenosis ≥ to 80% at time of enrollment.
27. Rheumatic heart disease including rheumatic mitral stenosis.
28. Pregnant or lactating at the time of enrollment (women of childbearing age should have negative pregnancy test within 72 hours of surgery) or planning pregnancy within the next 12 months.
29. Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator.
30. Condition or conditions that, in the opinion of the Investigator, precludes participation, including willingness to comply with all follow-up procedures.
31. Contraindication for transesophageal echocardiography (TEE), including esophageal spasm, esophageal stricture, esophageal laceration, esophageal perforation, esophageal diverticula (e.g. Zenker's diverticulum).
32. Echocardiographic evidence of intracardiac mass (e.g. left ventricular, atrial, or appendage thrombus, myxoma, or vegetation).

33. Cannot tolerate procedural anticoagulation or post-procedure antiplatelet regimen.

    Intra-operative exclusion criteria

34. No longer meets eligibility criteria based on intra-operative assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HARPOON™ Beating Heart Mitral Valve Repair System; Subjects who were treated with the HARPOON™ Beating Heart Mitral Valve Repair System	Device: HARPOON™ Beating Heart Mitral Valve Repair System; Repair of the chordae tendinae in the mitral valve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NYHA classification from Baseline to 5 years	The New York Heart Association (NYHA) functional classification system relates symptoms to everyday activities and the patient's quality of life. Class I. Patients with cardiac disease but without resulting limitation of physical activity. Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest.	Baseline compared to 1 and 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Product Usage	Blood product usage intraoperatively or post-operatively until discharge, in the HARPOON System treatment arm vs. open surgery.	Intraoperatively or post-operatively until discharge
Procedure Time	Procedure time: first incision to incision close time in the HARPOON System treatment arm vs. open surgery.	First incision to incision close time
OR Time	OR time: entry to OR suite and exit from OR suite in the HARPOON System treatment arm vs. open surgery.	Entry to OR suite and exit from OR suite
Total Ventilation Hours	Total ventilation hours at discharge in the HARPOON System treatment arm vs. open surgery.	Discharge
Total Hours in ICU	Total hours in the ICU post index procedure until discharge in the HARPOON System treatment arm vs. open surgery.	Post index procedure until discharge
Percentage of subjects receiving mitral valve replacement (MVR)	Percentage of subjects receiving mitral valve replacement (MVR) during the index procedure in the HARPOON System treatment arm vs. open surgery.	During Index Procedure
Hospital Length of Stay (LOS)	Hospital length of stay (LOS) post index procedure until discharge in the HARPOON System treatment arm vs. open surgery.	Post index procedure until discharge
Composite Effectiveness Endpoint	Composite effectiveness endpoint, defined as freedom from all-cause mortality, re-intervention on the mitral valve and recurrent (moderate or severe) mitral regurgitation (MR) for one year following the index procedure, in the HARPOON System treatment arm vs. CTSN-TR comparator.	One year following the index procedure
Discharged to Home vs. Other Facility	Discharged to home vs. other facility, in the HARPOON System treatment arm vs. open surgery.	Discharge

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Vinod H. Thourani, MD, Dept of Cardiovascular Surgery, Piedmont Heart Institute; Principal Investigator: Konstantinos Koulogiannis, MD, Department of Cardiovascular Medicine Gagnon Cardiovascular Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Estimated): December 20, 2027
• Study Completion (Estimated): December 20, 2027

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 2019-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes