TWIST II Pivotal Trial

Overview

About this study

The purpose of this study is to establish the safety and effectiveness of the INNOVALVE system in patients with symptomatic, moderate-severe to severe MR for whom commercially available surgical and TEER options are deemed unsuitable due to clinical, anatomic, or technical considerations.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • 18 years of age or older

  • Mitral/cardiac anatomy that will enable safe and effective delivery and deployment of the INNOVALVE system

  • Moderate-to-severe or severe (≥ 3+) degenerative MR (DMR) or functional MR (FMR) by echocardiography (transthoracic echocardiography [TTE] or transesophageal echocardiography [TEE])

  • New York Heart Association Class ≥ II

  • Patient’s heart failure management has been optimized based on patient characteristics and applicable guidelines, and medications have been stable for at least 30 days prior to enrollment. Note: Patients who require significant changes to heart failure medications after enrollment but prior to the procedure must restabilize for 30 days to be eligible

  • Per the Heart Team, commercially available surgical and TEER options are deemed unsuitable due to clinical, anatomic, or technical considerations

  • Patient is willing and able to comply with all study evaluations and provides written informed consent

Exclusion Criteria:

  • Mitral valve/cardiac anatomy that will preclude safe and effective delivery or deployment of the INNOVALVE system, including, but not limited to:

    • Significant prolapse or other leaflet anatomy that may lead to suboptimal results

    • Moderate or severe mitral annular calcification (MAC)

    • Left ventricular end-diastolic diameter ≥ 75 mm

    • Significant risk of LVOT obstruction

  • Inappropriate anatomy for femoral introduction and delivery of the INNOVALVE system

  • Presence of any device that will preclude safe and effective delivery or deployment of the INNOVALVE system

  • Previous mitral intervention that could interfere with placement or function of the INNOVALVE system

  • Need for emergent or urgent surgery for any reason, or planned surgery requiring prolonged recovery or inactivity and/or reduced mobility within the next 365 days (1 year)

  • Any of the following cardiovascular procedures or other devices or procedures that may affect procedural outcomes:

    • Percutaneous coronary, intracardiac, or endovascular intervention within 30 days

    • Carotid surgery within 30 days

    • Direct current cardioversion within 30 days

    • Pacemaker or ICD implantation within 30 days

    • Left atrial appendage occlusion placement within 30 days

    • Ablation for atrial fibrillation or ventricular arrhythmias within 30 days

    • Cardiac surgery within 90 days

  • Severe aortic, tricuspid, and/or pulmonary valve stenosis and/or regurgitation

  • Severe right ventricular (RV) dysfunction

  • Left ventricular ejection fraction < 25%

  • Presence of infiltrative cardiomyopathy or valvulopathy (including carcinoid, amyloidosis, sarcoidosis, hemochromatosis) or uncorrected, significant congenital heart disease (including, but not limited to, ventricular septal defects)

  • Patients with refractory heart failure requiring or that required advanced intervention (i.e., left ventricular assist device, prior heart transplant, heart transplant status ≤ 5 or equivalent)

  • Recent hemodynamic instability (e.g., need for inotropic support, intraaortic balloon pump, or other hemodynamic support device)

  • Clinically significant, untreated coronary artery disease (CAD) requiring revascularization, unstable angina, evidence of acute coronary syndrome, or recent myocardial infarction (per World Health Organization [WHO] definition)

  • Echocardiographic evidence of significant intra-cardiac mass, thrombus, or vegetation

  • Active bacterial endocarditis

  • Infection requiring current antibiotic therapy (oral or intravenous) within 14 days

  • Recent stroke or transient ischemic attack (TIA)

  • Modified Rankin Scale (mRS) ≥ 4 disability

  • Estimated pulmonary artery systolic pressure (PASP) > 70 mmHg assessed by site based on echocardiography or right heart catheterization (RHC), unless a vasodilator challenge is able to reduce pulmonary vascular resistance (PVR) to < 3 Wood units, or to between 3 and 4.5 Wood units with a V wave less than twice the mean pulmonary capillary wedge pressure

  • Chronic pulmonary disease requiring home oxygen therapy or chronic outpatient oral steroid use

  • Severe renal insufficiency with estimated glomerular filtration rate (eGFR) ≤ 25 mL/min/1.73 m2 or requiring renal replacement therapy

  • Patients with hepatic insufficiency or cirrhosis with Child-Pugh Score class B or C

  • Untreatable hypersensitivity or contraindication to any of the following: all antiplatelets, all anticoagulants, nitinol alloys (nickel and titanium), bovine tissue, glutaraldehyde, or contrast media

  • Known bleeding or clotting disorders or patient refuses blood products

  • Deep vein thrombosis or pulmonary embolism

  • Chronic anemia with transfusion dependency or hemoglobin < 9 g/dL not corrected by transfusion

  • Recent, active gastrointestinal bleeding

  • Thrombocytopenia (platelet count < 75,000/mm3) or thrombocytosis (platelet count > 750,000/mm3) 29 Patients in whom any of the following is true:

    • A TEE is contraindicated or cannot be completed

    • Mitral valve anatomy is not evaluable by TTE or TEE

    • Screening TEE imaging is sub-optimal for visibility and guidance during the procedure and follow-up evaluations

  • Pregnant, breastfeeding, or planning pregnancy within next 365 days (1 year)

  • Any physical impairment limiting the patient’s capacity to complete functional testing due to other medical conditions independent of their MR (e.g., orthopedic condition)

  • Comorbid condition(s) that, in the opinion of the Investigator, limit life expectancy to < 365 days (1 year)

  • Patients currently participating in another investigational biologic, drug, or device clinical study, and the patient has not reached the primary study endpoint

  • Any condition, in the opinion of the Investigator, that may prevent the patient from completing all protocol procedures and follow-up visits

  • Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including being under guardianship

  • Patients considered to be part of a vulnerable population as defined in ISO 1455

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 01/20/2026. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mackram Eleid, M.D.

Contact us for the latest status

Contact information:

Structural Heart Disease Research Coordinators

(507) 255-6133

More information

Publications

Publications are currently not available
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CLS-20600364

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