TEER for Severe DMR of Low to Intermediate Surgery Risk

The Efficacy and Safety of TEER for Severe DMR Patients of Low to Intermediate Surgery Risk (TESLA-R)--a Multi-center, Prospective Cohort Study

To investigate the efficacy and safety of transcatheter mitral valve edge-to-edge repair (TEER) for severe degenerative mitral regurgitation (DMR) patients of low to intermediate surgery risk.

Study Overview

• Status: Recruiting
• Conditions: Mitral Regurgitation
• Intervention / Treatment: Diagnostic test: ultrasonic cardiography (UCG); Procedure: TEER

Detailed Description

This is a proposed multicentre, prospective cohort study to enrol and follow up severe DMR patients of low to intermediate surgery risk who underwent TEER, and surgical historical controls. The primary efficacy endpoints are all-cause death and cumulative composite event rate of worsening heart failure at 24 months postoperatively, and the primary safety endpoints are death, secondary surgery, and various complications at 30 days postoperatively. The study aims to investigate the efficacy and safety of TEER in surgical low-intermediate-risk patients with severe DMR, and to inform the subsequent clinical application.

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Yangxin Chen, PhD; Phone Number: 8681332360; Email: chenyx39@mail.sysu.edu.cn
• Study Contact Backup: Name: Maohuan Lin; Phone Number: 8681332360; Email: chenyx39@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
      • Contact: Yangxin Chen, PhD; Phone Number: 8681332360; Email: chenyx39@mail.sysu.edu.cn
      • Principal Investigator: Yangxin Chen, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

severe DMR patients of low to intermediate surgery risk who underwent TEER.

Description

Inclusion Criteria: the patient fully meets the following criteria.

1. age ≥ 18 years old
2. DMR ≥ grade 3+ according to UCG integrative approach, referring to the following quantitative indicators: 1) effective regurgitant orifice area (EROA) ≥0.3cm^2; 2) regurgitant volume (RVol) ≥45ml; 3) regurgitant fraction (RF) ≥40%.
3. symptomatic heart failure ( New York Heart Association (NYHA) class II-IV ), or asymptomatic heart failure with left ventricular end systolic dimension (LVESd) ≥40mm or ejection fraction (EF) ≤60%, or new-onset atrial fibrillation, or resting pulmonary artery systolic pressure (PASP) >50mmHg.
4. The patient with American Association of Thoracic Surgeons Score (STS) <8 has surgical indications evaluated by cardiac team.
5. The patient has signed an informed consent form and agreed to regular follow-up for at least 1 year.

Exclusion Criteria: the patient meets any of the following criteria.

1. active infective endocarditis especially occurring in the mitral valve area, or mitral valve perforation.
2. rheumatic mitral valve disease, mitral stenosis or mitral valve orifice area < 4mm^2.
3. combined valve lesions requiring surgery, e.g. severe tricuspid regurgitation or aortic valve disease.
4. the present of tumour, thrombus or redundant organisms in the heart chambers.
5. inability to tolerate intraoperative or postoperative antithrombotic (anticoagulant or antiplate) therapy.
6. acute DMR, e.g. DMR caused by acute papillary muscle rupture.
7. Due to the presence of certain anatomical conditions, patient has a low success rate for TEER assessed by the operator and is not appropriate for enrolment. The conditions include but are not limited to the followings: 1) the venous approach is not suitable for operation, such as thrombus in the approach and small vein diameter; 2) severe calcification presents in the flap leaflet clamping area; 3) mitral valve cleft; 4) multiple regurgitant flow, especially in the internal and external union junction area; 5) Barlow disease; 6) leaflet length <7mm; 7) flail gap >10mm; 8) flail width >15mm.
8. severe cardiac insufficiency ( NYHA class IV or lefr ventricular ejection fraction (LVEF) <20% ), end-stage heart failure status ( American College of Cardiology/American Heart Association (ACC/AHA) Stage D), relying on circulation aids or waiting for heart transplantation.
9. proposed implantation of heart failure device such as cardiac resynchronization therapy/cardiac resynchronization therapy defibrillator (CRT/CRT-D) or cardiac contractility modulation (CCM).
10. untreated severe coronary artery stenosis requiring coronary revascularization, or other cardiac macrovascular disease requiring surgery.
11. hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or structural heart disease leading to heart failure other than dilated heart disease.
12. severe pulmonary hypertension ( PASP >70 mmHg), or pulmonary hypertension associated with no-left heart disease, e.g. pulmonary arterial hypertension (PAH) etc.
13. acute myocardial infarction within 4 weeks before operation.
14. acute cerebrovascular accident within 30 days before operation.
15. acute peptic ulcer or upper gastrointestinal bleeding within 3 months before operation.
16. uncontrolled hyperthyroidism.
17. uncontrolled autoimmune connective tissue diseases especially Behcet's disease and systemic lupus erythematosus (SLE).
18. amyloidosis.
19. severe infections, septicaemia.
20. severe hepatic insufficiency, e.g. acute severe hepatitis, decompensated cirrhosis ( Child-Pugh class C)
21. severe renal insufficiency ( chronic kidney disease (CKD) stage 5: estimated glomerular filtration rate (eGFR) < 15 ml/min or dialysis).
22. hypotensive state, shock ( systolic blood pressure < 90mmHg or mean arterial pressure <70 mmHg with tissue hypoperfusion and urine output < 30 ml/h).
23. uncontrolled diseases of the haematological system: acute gastrointestinal bleeding, intracranial haemorrhage or haemorrhage from other organs, acute pulmonary embolism or deep vein thrombosis, congenital or acquired haemorrhagic disease such as haemophilia, anaphylactic purpura and acute leukaemia, severe abnormalities in haematological parameters such as platelet count <20*10^9/L and international normalized ratio (INR) >3.
24. contraindication for TEE, e.g. oesophageal constriction, oesophageal tumour, oesophageal fistula, oesophageal varices, cervical vertebral instability, etc.
25. contraindication for intravenous anaesthesia, e.g. allergy to anaesthetics.
26. pregnancy or breastfeeding.
27. The patient does not sign an informed consent form.
28. expected survival less than 1 year.
29. The patient with poor compliance is not thought to complete follow-up visits.
30. The patient is participating in an experimental drug or other device study with an incomplete primary endpoint, or the patient is participating in an unfinished experimental drug or other device study that would clinically interfere with our study endpoints.
31. Due to other reasons the patient is not suitable for enrollment assessed by the researcher.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

TEER group; Severe DMR patients of low to intermediate surgery risk who underwent TEER.

Diagnostic test: ultrasonic cardiography (UCG); Trans-thoracic echocardiography (TTE) is performed in the resting position. Trans-esophageal echocardiography (TEE) is performed under surface anaesthesia with bupivacaine or intravenous anaesthesia. We comprehensively assess the severity of mitral regurgitation according to American Society of Echocardiography (ASE) guideline.; Procedure: TEER; Two commercial cliping systems are available for clinical use: the G3 MitraclipTM and the G4 MitraclipTM (Abbott), DragonflyTM (Dejin), which will be introduced to the Chinese market in 2024, with the specific choice determined by the operator. The patient receives general anaesthesia (intravenous and endotracheal). The operator performs the procedure according to the recommended surgical steps in the product manual, guided by X-ray and trans-esophageal echocardiography. Postoperative MR ≤2+ is considered successful, and if the result is unsatisfactory, 1-2 additional clips are given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cumulative composite event rate of all-cause death and worsening heart failure	all-cause mortality: deaths from all causes including cardiovascular and non-cardiovascular deaths. worsening heart failure: heart failure rehospitalization, worsening heart failure needing emergency room visit, NYHA classification increased by one, ineffective escalation of medication on outpatient service, receiving intravenous diuretic therapy on outpatient or emergency service.	time of operation to 24 months after operation
cumulative composite event rate of the main adverse events	The main adverse events: death, acute myocardial infarction, requiring secondary therapy for valve treatment failure, requiring non-scheduled cardiovascular emergency surgery for main complications, stroke, kidney failure, deep infection, >48 hours mechanical ventilation, new-onset atrial fibrillation, deep vein thrombosis, pulmonary embolism, sepsis, haemorrhage, blood transfusion >2U	time of operation to 30 days after operation

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; First Affiliated Hospital Xi'an Jiaotong University; Third Affiliated Hospital, Sun Yat-Sen University; ZhuZhou Central Hospital; Fifth Affiliated Hospital, Sun Yat-Sen University; People's Hospital of Xinjiang Uygur Autonomous Region; The First Affiliate Hospital of Guangxi Medical College; First People's Hospital of Foshan; Peking University Shenzhen Hospital; Dongguan People's Hospital; Southern Medical University, China; Shantou Central Hospital; Sichuan Provincial People's Hospital; Zhongshan People's Hospital, Guangdong, China; The First Affiliated Hospital of Shantou University Medical College; Jiangmen Central Hospital; Meizhou People's Hospital; Suzhou Municipal Hospital; Yueyang Central Hospital; The Second People's Hospital of Foshan; People's Hospital of Nanhai District, Foshan; The General Hospital of Southern Theater Command; Huizhou The Third People's Hospital; Central South University Xiangya Hospital; Affiliated Hospital of Guangdong Medical University; Guangzhou Panyu Center Hospital; Nanfang Hosptial, China; Foshan Fosun Chancheng Hospital
• Investigators: Principal Investigator: Yangxin Chen, PhD, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: degenerative mitral regurgitation; transcatheter mitral valve edge-to-edge repair; surgery risk
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: SYSKY-2023-1019-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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.: No