A Clinical Trial of the Transcatheter Aortic Valve Implantation System With a Prospective, Multi-Center, One-Arm Approach to Evaluate the Efficacy and Safety in the Treatment of Patients With Severe Aortic Stenosis

A Clinical Trial of the Transcatheter Aortic Valve Implantation System with a Prospective, Multi-Center, One-Arm Approach to Evaluate the Efficacy and Safety in the Treatment of Patients with Severe Aortic Stenosis

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Stenosis
• Intervention / Treatment: Device: Transcatheter Aortic Valve Implantation (KOKA-VALVE)

Detailed Description

This trial consists of two parts. Part I, the Feasibility trial: 10-12 patients with severe aortic stenosis who meet inclusion/exclusion criteria and are at high surgical risk or not suitable for conventional surgical valve replacement are selected at no more than 5 centers for implantation of an aortic valve by transcatheter aortic valve replacement (KOKA-VALVE) to achieve treatment of aortic valve disease in subjects. All-cause mortality at 30 days after implantation is used as the primary endpoint, and the immediate postoperative device success and surgical success, major cardiovascular adverse events at 1 year after implantation, transvalvular pressure difference at 30 days and 12 months after implantation, degree of orifice regurgitation, degree of perivalvular leakage, improvement in NYHA cardiac function, and improvement in quality of survival are used as the secondary endpoints to supplementarily evaluate the safety and feasibility of this product. It also provides experience and reference for further Part II confirmatory trials and applications to ensure safe conduct of confirmatory trials. Subjects in the feasibility trial may continue to be followed up at 6 months after implantation and 12 months after implantation after completion of the one-month postoperative follow-up. All subjects will also continue to be followed up by telephone at 24, 36, 48, and 60 months after implantation.

Part II, the Confirmatory Trial: Designed with a prospective, multi-center, one-arm approach. 131 patients with severe aortic stenosis who meet inclusion/non-exclusion criteria and are at high surgical risk or unsuitable for conventional surgical valve replacement are implanted with an aortic valve by transcatheter aortic valve replacement (KOKA-VALVE) to achieve treatment of aortic valve disease in subjects. All-cause mortality at 30 days after implantation is used as the primary endpoint, and the immediate postoperative device success and surgical success, major cardiovascular adverse events at 1 year after implantation, transvalvular pressure difference at 30 days and 12 months after implantation, degree of orifice regurgitation, degree of perivalvular leakage, improvement in NYHA cardiac function, and improvement in quality of survival are used as the secondary endpoints to supplementarily evaluate the safety and feasibility of this product.

All patients will be followed up before discharge, 30 days, 6 months, and 12 months after implantation after product implantation. All subjects will be followed up by telephone at 24 months, 36 months, 48 months and 60 months after implantation.

The study will be conducted at multiple clinical trial sites nationwide, and 131 subjects will be enrolled in the confirmatory trial. The enrollment and treatment status of the subjects will be recorded during the study, and the subjects will be followed up before discharge, 6 months after implantation, and 12 months after implantation, and the data will be compiled for registration and declaration.

All subjects will be followed up by telephone at 24 months, 36 months, 48 months, and 60 months after implantation.

• Study Type: Interventional
• Enrollment (Anticipated): 131
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chunrui Xiang; Phone Number: +86 17601425727; Email: crxiang@kokalife.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Structral Heart Disease Center, Fuwai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Contraindication to surgery, or high risk for surgery (STS ≥ 8%) as assessed by the heart team; or other circumstances that make surgical valve replacement inappropriate.
• Age ≥65 years.
• Patients with symptomatic severe aortic stenosis (mean aortic transvalvular gradient by echocardiography ≥40 mmHg (1 mmHg=0.133 kPa), or transaortic flow velocity ≥4.0 m/s, or aortic valve orifice area <0.8 cm2, or effective aortic orifice area index <0.5 cm2 /m2).
• The subjects have been informed of the nature of this study, understand the purpose of the clinical trial, and voluntarily participate in and sign the informed consent form.

Exclusion Criteria:

• Life expectancy less than 1 year after implantation of the prosthetic valve.
• Patients had an acute heart attack within 1 month, or had a coronary stent or a pacing device implantation within 1 month, or had any therapeutic cardiac surgery within 1 month.
• Patients with aortic root anatomy and lesion that are not suitable for prosthetic valve implantation.
• Combined with severe insufficiency or stenosis of other valves and requiring surgical treatment.
• Hematologic cachexia, including leukopenia (WBC <3×10^9 /L), acute anemia (HB <90 g/L), thrombocytopenia (PLT <50 × 10^9 /L), bleeding constitution, and coagulation disorders.
• Untreated coronary artery disease requiring hematologic reconstruction.
• Hypertrophic obstructive cardiomyopathy.
• Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) <20%.
• Severe right ventricular insufficiency.
• The existent of intracardiac masses, thrombi or superfluous organisms by echocardiography.
• Patients who cannot tolerate anticoagulation or antiplatelet therapy.
• Patients had cerebrovascular event (CVA), including ischemic stroke and hemorrhagic stroke within 3 months.
• Decompensation of renal insufficiency.
• Active infective endocarditis or other active infection.
• Untreated conduction system disease requiring pacemaker implantation.
• Currently participating in an investigational drug or another device study that has not completed its primary endpoints or would clinically interfere with the endpoint of this study.
• Other circumstances that are assessed by the investigator to be unsuitable for interventional aortic valve therapy.

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: Treatment Group	Device: Transcatheter Aortic Valve Implantation (KOKA-VALVE); Transcatheter Aortic Valve Implantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Cumulative all-cause mortality at 12 months postoperatively	12 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transvalvular Gradient	Transvalvular Gradients at 30 days and 12 months postoperatively	30 days and 12 months postoperatively
Aortic Regurgitation Degree	Aortic Regurgitation Degree at 30 days and 12 months postoperatively	30 days and 12 months postoperatively
Perivalvular Leakage	Perivalvular Leakage at 30 days and 12 months postoperatively	30 days and 12 months postoperatively
Cardiac Function	The rate of New York Heart Association (NYHA) Function Class at 30 days and 12 months postoperatively	30 days and 12 months postoperatively
Quality of Survival	The score of EQ-5D at 30 days and 12 months postoperatively	30 days and 12 months postoperatively

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): December 30, 2022
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): December 30, 2028

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Estimate): January 6, 2023

Study Record Updates

• Last Update Posted (Estimate): January 6, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Heart Valve Disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: KOKA-2022-03

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