Comparison of Transcatheter Edge-to-edge Repair Using Echo Only with Echo Combined with X Ray for Mitral Regurgitation (ECHO-CLIP)

A Randomized Clinical Trial of Transcatheter Edge-to-edge Repair for Mitral Regurgitation Under Fully Echocardiographic Guidance Compared with Under Combined Guidance of Both Echocardiography and Fluoroscopy (ECHO-CLIP Study)

Mitral regurgitation (MR) is a common valvular heart disease in the elderly population, frequently associated with poor prognosis if not treated. Transcatheter edge-to-edge repair (TEER) has recently emerged as a popular strategy due to minimal invasiveness. What's more, previous studies, such as EVEREST II and COAPT study, have demonstrated its efficacy in high-risk patients with primary or secondary MR. Conventional TEER procedure, however, is performed under combined guidance of both echocardiography and fluoroscopy, which potentially results in high radiation exposure and limits its application. Since 2021 2021, the investigators have changed the procedural methodology by performing TEER under full echocardiographic guidance on accumulated dozens of MR patients successfully. To confirm the efficacy of a fully echo-guided TEER procedure, the investigators conduct the ECHO-CLIP study to compare its outcomes with the conventional TEER procedure, as well as evaluate the outcomes of this novel methodology in special populations with radiation contraindications. ECHO-CLIP study is a prospective, multicenter, open-label, noninferior, randomized controlled trial of TEER by two different methodological strategies in treating severe primary or secondary MR. It is anticipated to enroll a total of 200 patients as well to complete the enrollment before Dec 31, 2025 and the follow-up before Dec 31, 2026. This work will potentially demonstrate the feasibility and efficacy of the fully echo-guided TEER procedure, thereby revolutionizing the TEER methodology and benefiting more patients.

Study Overview

• Status: Recruiting
• Conditions: Mitral Regurgitation
• Intervention / Treatment: Procedure: Echocardiographic guidance; Procedure: Fluoroscopic guidance

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiangbin Pan; Phone Number: 8688396666; Email: panxiangbin@fuwaihospital.org
• Study Contact Backup: Name: Jianrui Ma; Phone Number: 8688396666; Email: Jianrui0705@163.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen
      • Contact: Xiangbin Pan; Phone Number: 86-0755-82180028; Email: panxiangbin@fuwaihospital.org
      • Contact: Fuwai Hospital Fuwai Hospital，Chinese Academy of Medical Sciences
      • Contact: Shouzheng Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

*Subjects meet either the first or second inclusion criteria in combination with the third and fourth ones were eligible.

1. Symptomatic DMR subjects with MR ≥ 3+ at high surgical risk in terms of STS Predicted Risk of Mortality replacement score ≥ 8 or STS Predicted Risk of Mortality repair score ≥ 6.*
2. FMR subjects with LVESD ≤ 70 mm and MR ≥ 3+, despite administration of GDMT for 30 days.*
3. MV anatomy appropriate for TEER procedure.
4. Subjects willing to participate in this study and complete the follow-up on schedule after obtaining informed consent.

Exclusion Criteria:

1. Myocardial infarction within 12 weeks prior to randomization.
2. Need for concurrent other cardiac procedures.
3. Any endovascular intervention or surgery within 30 days prior to randomization.
4. LVEF < 20%.
5. MV orifice area < 4.0 cm2.
6. Pulmonary artery systolic pressure > 70 mmHg, as determined by echocardiogram.
7. Severe mitral annular calcification.
8. Unsuitable MV anatomy potentially precluding clip implantation: leaflet calcification or significant leaflet cleft in the grasping zone.
9. Previous MV surgery or current implanted ventricular assist device or current implanted mechanical prosthetic valve.
10. Any intracardiac mass, thrombus, or vegetation, as evidenced by echocardiogram.
11. Active endocarditis or rheumatic heart disease.
12. History of DVT or PE.

Abbreviations: DMR, degenerative mitral regurgitation; MR, mitral regurgitation; STS, Society of Thoracic Surgeons; FMR, functional mitral regurgitation; LVESD, left ventricular end-systolic diameter; GDMT, guideline-directed medical therapy; TEER, transcatheter edge-to-edge repair; LVEF, left ventricular ejection fraction; MV, mitral valve; DVT, deep venous thrombosis; PE, pulmonary embolism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Echocardiography-guided group; Patients randomized to the echocardiography-guided group will undergo TEER procedure under fully echo guidance.	Procedure: Echocardiographic guidance; After detailed evaluation, patients randomized in this group will undergo TEER procedure under guidance of fully echocardiography but any fluoroscopy in the entire process.
Active Comparator: Fluoroscopy-guided group; Patients randomized to the fluoroscopy-guided group will undergo TEER procedure under combined guidance of X ray and echo.	Procedure: Fluoroscopic guidance; After detailed evaluation, patients randomized in this group will undergo TEER procedure under combined guidance of echocardiography and fluoroscopy in the entire process.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day successful rate after device implantation (residual MR ≤2+)	The primary outcome is the success rate of device implantation at 30 days ( residual MR≤moderate). Evaluation of the primary endpoints was done by specialized sonographers blinded to the intervention.	At 30 days after device implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year all-cause mortality	All-cause mortality at 1 year after implantation.	At 1 year after implantation
1-year composite of death, reintervention, and recurrent MR ≥ 3+	Composite of death, reintervention, and recurrent MR ≥ 3+ at 1 year	At 1 year after implantation
Change in SF-36 score from baseline to 30 days and 1 year.	Change in 36-Item Short Form Survey score from baseline to 30 days and 1 year will be assessed. An increased score after implantation indicates an improvement in quality of life, while a decreased score after implantation indicates an impairment in quality of life.	At 30 days and 1 year after implantation
Change in KCCQ score from baseline to 30 days and 1 year.	Change in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days and 1 year wiil be assessed. An increased score after implantation indicates an improvement in quality of life, while a decreased score after implantation indicates an impairment in quality of life.	At 30 days and 1 year after implantation
Change in HADS score from baseline to 30 days and 1 year.	Change in Hospital Anxiety and Depression Scale score from baseline to 30 days and 1 year will be assessed. An increased score after implantation indicates an aggregation in psychological stress, while a decreased score after implantation indicates an improvement in psychological stress.	At 30 days and 1 year after implantation
Composite of major adverse events	Composite of major adverse events immediately after implantation, at 30 days, 3 months, and at 1 year including death, myocardial infarction, reintervention, nonelective cardiovascular surgery for adverse events, ventilation over 48 hours, gastrointestinal complications requiring surgery, new-onset permanent atrial fibrillation, sepsis, and transfusion of 2 or more units of blood.	Immediately after implantation, at 30 days, 3 months, and at 1 year
Left ventricular ejection fraction	Left ventricular ejection fraction at 30 days, 3 months, and 1 year	At 30 days, 3 months, and 1 year after implantation
Left ventricular end-diastolic volume and left ventricular end-systolic volume	Left ventricular end-diastolic volume and left ventricular end-systolic volume at 30 days, 3 months, and 1 year after implantation.	At 30 days, 3 months, and 1 year after implantation.
Left ventricular end-systolic diameter and left ventricular end-diastolic diameter	Left ventricular end-systolic diameter and left ventricular end-diastolic diameter at 30 days, 3 months, and 1 year after implantation	At 30 days, 3 months, and 1 year after implantation
NYHA functional classification	At 30 days, 3 months, and 1 year after implantation.	At 30 days, 3 months, and 1 year after implantation.
Regurgitant volume and regurgitant fraction	Regurgitant volume and regurgitant fraction at 30 days, 3 months, and 1 year.	At 30 days, 3 months, and 1 year after implantation
Device implantation rate	Device implantation rate.	At 30 days after device implantation
Vascular complications	Vascular complications at 30 days, 3 months, and 1 year including access-site hematoma > 6 cm, arteriovenous fistula, symptomatic peripheral ischemia or nerve injury with symptoms or signs over 48 hours, access-site vascular injury requiring surgical repair, PE, ipsilateral DVT, access-site associated infection requiring antibiotics injection or prolonging hospital stay.	At 30 days, 3 months, and 1 year after implantation
Major bleeding events	Major bleeding events at 30 days, 3 months, and at 1 year after implantation that is defined as any procedure-related bleeding requiring transfusion of 2 or more units of blood and/or surgical repair	At 30 days, 3 months, and at 1 year after implantation
Arrhythmia	Arrhythmia at 30 days, and at 1 year after implantation	At 30 days and 1 year after implantation
Infective Endocarditis	Infective Endocarditis at 30 days, 3 months, and at 1 year after implantation according to the Duke Criteria.	At 30 days, 3 months and 1 year after implantation
Thrombotic events	Thrombotic events at 30 days, 3 months, and at 1 year after implantation.	At 30 days, 3 months, and at 1 year after implantation
Hemolytic events	Hemolytic events at 30 days, 3 months, and at 1 year after implantation.	At 30 days, 3 months, and at 1 year after implantation
Iatrogenic atrial septal defect	Iatrogenic ASD at 30 days, 3 months, and at 1 year after implantation.	At 30 days, 3 months, and at 1 year after implantation.
Single leaflet device attachment	Single leaflet device attachment at 30 days, 3 months, and at 1 year after implantation.	At 30 days, 3 months, and at 1 year after implantation.
Mitral Stenosis	Mitral stenosis at 30 days, 3 months, and at 1 year after implantation that is defined as mitral valve area < 1.5 cm2.	At 30 days, 3 months, and at 1 year after implantation.
Mitral valve area	Mitral valve area at 30 days, 3 months, and at 1 year after implantation.	At 30 days, 3 months, and at 1 year after implantation.
Transmitral pressure gradient	Transmitral pressure gradient at 30 days, 3 months, and at 1 year after implantation	At 30 days, 3 months, and at 1 year after implantation
Hospital stay after implantation	Hospital stay after implantation	At study completion with an average of 1 year
ICU stay after implantation	ICU stay after implantation	At study completion with an average of 1 year
30-day rehospitalization for heart failure	Rehospitalization for heart failure at 30 days after implantation	At 30 days after implantation
New Warfarin Use	New Warfarin Use at 30 days and 1 year after device Implantation	At 30 days and 1 year after implantation
Hospital cost	Hospital cost	At study completion with an average of 1 year
Procedure time and radiation time	Procedure time and radiation time	At study completion with an average of 1 year

Collaborators and Investigators

• Sponsor: Pan Xiangbin
• Investigators: Principal Investigator: Xiangbin Pan, Chinese Academy of Medical Sciences, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 8, 2024
• First Posted (Estimated): November 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: ultrasound; mitral regurgitation; echo; transcatheter edge-to-edge repair; ECHO-CLIP; randomized clinical trail
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: NO.SP2024005(01)A

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: No
• product manufactured in and exported from the U.S.: No