AzTrials
AzTrials

Aortic StenosisREPRISE IIINCT02202434

Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement

A study testing Lotus Valve System, CoreValve/Evolut R Transcatheter Aortic Valve Replacement System and LOTUS Edge Valve System in people with Aortic Stenosis, run by Boston Scientific Corporation at 58 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The objective of this study is to evaluate the safety and effectiveness of the Lotus™ Valve System and LOTUS Edge™ Valve System for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with calcific, severe native aortic stenosis who are considered at extreme or high risk for surgical valve… Read more about this study

Who is it for?
Any age
Conditions the study is for
Aortic Stenosis
What is being tested?
Lotus Valve System, CoreValve/Evolut R Transcatheter Aortic Valve Replacement System and LOTUS Edge Valve System
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,425 participants
Where
58 sitesin 6 countries
Study dates
22 Sep 2014to 21 May 2021
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subject has documented calcific, severe native aortic stenosis with an initial aortic valve area (AVA) of ≤1.0 cm2 (or AVA index of ≤0.6 cm2/m2) and a mean pressure gradient >40 mm Hg or jet velocity >4.0 m/s, as measured by echocardiography and/or invasive hemodynamics
  • Subject has a documented aortic annulus size of ≥18 mm and ≤29 mm based on the center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee [CRC]) and, for the randomized cohort, is deemed treatable with an available size of both test and control device. For the U.S. Continued Access Study cohort the acceptable aortic annulus size is ≥20 mm and ≤27 mm.
  • Subject has symptomatic aortic valve stenosis with New York Heart Association (NYHA) Functional Class ≥ II
  • There is agreement by the heart team (which must include a site investigator interventionalist and a site investigator cardiac surgeon) that subject is at high or extreme operative risk for surgical valve replacement (see note below for definitions of extreme and high risk, the required level of surgical assessment, and CRC confirmation) and that TAVR is appropriate. Additionally, subject has at least one of the following.
  • Society of Thoracic Surgeons (STS) score ≥8% -OR-
  • If STS <8, subject has at least one of the following conditions: Hostile chest, porcelain aorta, severe pulmonary hypertension (>60 mmHg), prior chest radiation therapy, coronary artery bypass graft(s) at risk with re-operation, severe lung disease (need for supplemental oxygen, forced expiratory volume in 1 second [FEV1] <50% of predicted, diffusing capacity of the lungs for carbon monoxide [DLCO] <60%, or other evidence of severe pulmonary dysfunction), neuromuscular disease that creates risk for mechanical ventilation or rehabilitation after surgical aortic valve replacement, orthopedic disease that creates risk for rehabilitation after surgical aortic valve replacement, Childs Class A or B liver disease (subjects with Childs Class C disease are not eligible for inclusion in this trial), frailty as indicated by at least one of the following: 5-meter walk >6 seconds, Katz Assessment of Daily Living (Katz ADL) score of 3/6 or less, body mass index <21, wheelchair bound, unable to live independently, age ≥90 years, other evidence that subject is at high or extreme risk for surgical valve replacement (CRC must confirm agreement with site heart team that subject meets high or extreme risk definition)
Show all 10Show fewer
  • Heart team (which must include a cardiac interventionalist and an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement.
  • Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent.
  • Subject, family member, and/or legal representative agree(s) and subject is capable of returning to the study hospital for all required scheduled follow up visits.
  • Note: Extreme operative risk and high operative risk are defined as follows: Extreme Operative Risk: Predicted operative mortality or serious, irreversible morbidity risk ≥50% at 30 days; High Operative Risk: Predicted operative mortality or serious, irreversible morbidity risk ≥15% at 30 days. Risk of operative mortality and morbidity must be assessed via an in-person evaluation by a center cardiac surgeon and must be confirmed by the CRC (which must include an experienced cardiac surgeon).

Who cannot join

  • Subject has a congenital unicuspid or bicuspid aortic valve.
  • Subject has had an acute myocardial infarction (MI) within 30 days prior to the index procedure (defined as Q-wave MI or non-Q-wave MI with total creatine kinase (CK) elevation ≥ twice normal in the presence of creatine kinase-myoglobin band (CK-MB) elevation and/or troponin elevation).
  • Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months prior to study enrollment.
  • Subject has end-stage renal disease or has glomerular filtration rate (GFR) <20 (based on Cockcroft-Gault formula).
  • Subject has a pre-existing prosthetic aortic or mitral valve.
  • Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
Show all 26Show fewer
  • Subject has a need for emergency surgery for any reason.
  • Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.
  • Subject has echocardiographic evidence of new intra-cardiac mass, vegetation or intraventricular or paravalvular thrombus requiring intervention.
  • Subject has (hemoglobin) Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3.
  • Subject requires chronic anticoagulation therapy after the implant procedure and cannot be treated with warfarin (other anticoagulants are not permitted in the first month) for at least 1 month concomitant with either aspirin or clopidogrel.
  • Subject has had a gastrointestinal bleed requiring hospitalization or transfusion within the past 3 months, or has other clinically significant bleeding diathesis or coagulopathy that would preclude treatment with required antiplatelet regimen, or will refuse transfusions.
  • Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all P2Y12 inhibitors, heparin, nickel, tantalum, titanium, or polyurethanes.
  • Subject has a life expectancy of less than 12 months due to non-cardiac, comorbid conditions based on the assessment of the investigator at the time of enrollment.
  • Subject has hypertrophic obstructive cardiomyopathy.
  • Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty or pacemaker implantation, which are allowed).
  • Subject has untreated coronary artery disease, which in the opinion of the treating physician is clinically significant and requires revascularization.
  • Subject has severe left ventricular dysfunction with ejection fraction <20%.
  • Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.
  • Subject has severe vascular disease that would preclude safe access (e.g., aneurysm with thrombus that cannot be crossed safely, marked tortuosity, significant narrowing of the abdominal aorta, severe unfolding of the thoracic aorta, or symptomatic carotid or vertebral disease).
  • Subject has thick (>5 mm) protruding or ulcerated atheroma in the aortic arch
  • Subject has arterial access that is not acceptable for the test and control device delivery systems as defined in the device Instructions For Use.
  • Subject has current problems with substance abuse (e.g., alcohol, etc.).
  • Subject is participating in another investigational drug or device study that has not reached its primary endpoint.
  • Subject has untreated conduction system disorder (e.g., Type II second degree atrioventricular block) that in the opinion of the treating physician is clinically significant and requires a pacemaker implantation. Enrollment is permissible after permanent pacemaker implantation.
  • Subject has severe incapacitating dementia.

Trial locations and contacts

58 sites in 6 countries.

58 sites in 6 countries

United States49 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University Hospital

    Atlanta, Georgia, 30308

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Union Memorial Hospital

    Baltimore, Maryland, 21218

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Kaleida Health

    Buffalo, New York, 14203

  • Lindner Center for Research and Education at The Christ Hospital

    Cincinnati, Ohio, 45219

  • Morton Plant Mease Healthcare System

    Clearwater, Florida, 33756

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Ohio Health Research and Innovation Institute - Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Baylor Heart and Vascular Hospital

    Dallas, Texas, 75226

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Delray Medical Center

    Delray Beach, Florida, 33484

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Evanston Hospital

    Evanston, Illinois, 60201

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Methodist DeBakey Heart & Vascular Center

    Houston, Texas, 77030

  • St. Vincent's Hospital

    Indianapolis, Indiana, 46290

  • University of Kansas Hospital

    Kansas City, Kansas, 66160

  • Scripps Clinic

    La Jolla, California, 92037

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • North Shore University Hospital

    Manhasset, New York, 11030

  • University of Miami Hospital

    Miami, Florida, 33136

  • Baptist Cardiac and Vascular Institute

    Miami, Florida, 33176

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Abbott Northwestern Hospital - Minneapolis Heart Institute

    Minneapolis, Minnesota, 55407

  • University of Minnesota Medical Center

    Minneapolis, Minnesota, 55455

  • Morristown Memorial Hospital

    Morristown, New Jersey, 07960

  • Columbia University Medical Center

    New York, New York, 10021

  • Veteran's Administration Palo Alto Medical Center

    Palo Alto, California, 94304

  • Cardiac & Vascular Rearch Center of Northern Michigan - Northern Michigan Hospital

    Petoskey, Michigan, 49770

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Banner Good Samaritan

    Phoenix, Arizona, 85018

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Providence St. Vincent Medical Center

    Portland, Oregon, 97225

  • NC Heart and Vascular Research - Rex Hospital

    Raleigh, North Carolina, 27607

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • University of California at Davis Medical Center

    Sacramento, California, 95817

  • Methodist Heart Hospital

    San Antonio, Texas, 78229

  • Scottsdale Healthcare - Shea

    Scottsdale, Arizona, 85258

  • University of Washington Medical Center

    Seattle, Washington, 98105

  • Swedish Medical Center

    Seattle, Washington, 98122

  • St. John's Hospital - Prairie Cardiovascular Consultants

    Springfield, Illinois, 62701

  • Washington University School of Medicine - Barnes Jewish Medical Center

    St Louis, Missouri, 63110

  • Stanford University Medical Center

    Stanford, California, 94305

  • Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Wake Forest University School of Medicine

    Winston-Salem, North Carolina, 27157

Other trials in United States

Australia2 sites

  • The Prince Charles Hospital

    Chermside, Queensland, 4032

  • Monash Medical Centre

    Clayton, Victoria, 3168

Other trials in Australia

Canada2 sites

  • McGill University Health Centre, Royal Victoria Hospital

    Montreal, Quebec, H3A

  • Providence Health - St. Paul's Hospital

    Vancouver, British Columbia, V6Z1Y6

Other trials in Canada

France2 sites

  • Clinique Pasteur

    Toulouse, Midi-Pyrenees, 31076

  • Centre Hôpital Universitaire Rangueil

    Toulouse, 31059

Other trials in France

Germany2 sites

  • Universitares Herzzentrum UKE (Hamburg)

    Hamburg, 20246

  • Herzzentrum Universität Leipzig

    Leipzig, Saxony, 04289

Other trials in Germany

Netherlands1 site

  • Erasmus MC - University Medical Center Rotterdam

    Rotterdam, 3015 CE

Other trials in Netherlands

About this study

Official title: REPRISE III: Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Randomized Clinical Evaluation

The objective of this study is to evaluate the safety and effectiveness of the Lotus™ Valve System and LOTUS Edge™ Valve System for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with calcific, severe native aortic stenosis who are considered at extreme or high risk for surgical valve replacement.

Conditions
Aortic Stenosis
Being tested
Lotus Valve System, CoreValve/Evolut R Transcatheter Aortic Valve Replacement System, LOTUS Edge Valve System
Medical subject headings
Aortic Valve Stenosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lotus Valve SystemDevice

    Procedure: Transcatheter aortic valve replacement (TAVR)

  • CoreValve/Evolut R Transcatheter Aortic Valve Replacement SystemDevice

    Procedure: Transcatheter aortic valve replacement (TAVR)

  • LOTUS Edge Valve SystemDevice

    Procedure: Transcatheter aortic valve replacement (TAVR)

Study groups in NCT02202434
Study groupRoleWhat they receive
Lotus Valve System - RandomizedExperimentalTranscatheter aortic valve replacement (TAVR) with Lotus Valve System
Receives: Device: Lotus Valve System
CoreValve TAVR System - RandomizedActive comparatorTranscatheter aortic valve replacement (TAVR) with CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Receives: Device: CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Lotus Valve Sytem - Single-arm 21mm CohortExperimentalTranscatheter aortic valve replacement (TAVR) with 21mm Lotus Valve System
Receives: Device: Lotus Valve System
Lotus Valve System - Single-arm Continued Access CohortExperimentalTranscatheter aortic valve replacement (TAVR) with Lotus Valve System
Receives: Device: Lotus Valve System
Lotus Valve System - Single-arm Roll-in CohortExperimentalTranscatheter aortic valve replacement (TAVR) with Lotus Valve System
Receives: Device: Lotus Valve System
LOTUS Edge Valve System - Single-arm Edge Nested RegistryExperimentalTranscatheter aortic valve replacement (TAVR) with 23mm, 25mm and 27mm LOTUS Edge Valve System.
Receives: Device: LOTUS Edge Valve System

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Events Included in the Primary Safety Endpoint

    Composite of all-cause mortality, stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, or major vascular complications

    Measured: 30 days following procedure

  2. Percentage of Participants With Events Included in the Primary Effectiveness Endpoint

    Composite of all-cause mortality, disabling stroke, or moderate or greater paravalvular aortic regurgitation (based on core lab assessment).

    Measured: 1 year following procedure

Secondary outcomes (1)

  1. Percentage of Participants With Moderate or Greater Paravalvular Aortic Regurgitation

    Moderate or greater paravalvular aortic regurgitation based on Independent echocardiographic core lab assessment performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation by Pibarot et al (J Am Coll Cardiol Img 2015: 8: 340-60). The grading scheme ranges from Trace (the least clinically significant) to severe (the most clinically significant).

    Measured: 1 year following procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2014 (estimated)
  2. Study start22 Sep 2014
  3. Primary completion8 Mar 2017
  4. Study completion21 May 2021

Why it stopped: RCT/Roll-in completed. CAS/21mm/Nested Registry terminated (investigational device is no longer available)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,425 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02202434
Sponsor's protocol ID
S2282
Acronym
REPRISE III
Status last verified
Dec 2021
First submitted
21 Jul 2014
Last updated
17 Dec 2021
Data monitoring committee
Yes

Publications

  • Rizik DG, Rajagopal V, Makkar RR, Bajwa T, Kleiman NS, Linke A, Kereiakes DJ, Waksman R, Thourani VH, Stoler RC, Mishkel GJ, Iyer VS, Buchbinder M, Gotberg M, Bjursten H, Allocco DJ, Reardon MJ. Long-term Outcomes of Transcatheter Aortic Valve Replacement With the Lotus Valve vs CoreValve/EvolutR: A Secondary Analysis of the REPRISE III Randomized Clinical Trial. JAMA Netw Open. 2022 Oct 3;5(10):e2238792. doi: 10.1001/jamanetworkopen.2022.38792.

    PubMed 36301543

  • Goel K, O'Leary JM, Barker CM, Levack M, Rajagopal V, Makkar RR, Bajwa T, Kleiman N, Linke A, Kereiakes DJ, Waksman R, Allocco DJ, Rizik DG, Reardon MJ, Lindman BR. Clinical Implications of Physical Function and Resilience in Patients Undergoing Transcatheter Aortic Valve Replacement. J Am Heart Assoc. 2020 Sep;9(17):e017075. doi: 10.1161/JAHA.120.017075. Epub 2020 Aug 28.

    PubMed 32856530

  • Meduri CU, Kereiakes DJ, Rajagopal V, Makkar RR, O'Hair D, Linke A, Waksman R, Babliaros V, Stoler RC, Mishkel GJ, Rizik DG, Iyer VS, Schindler J, Allocco DJ, Meredith IT, Feldman TE, Reardon MJ. Pacemaker Implantation and Dependency After Transcatheter Aortic Valve Replacement in the REPRISE III Trial. J Am Heart Assoc. 2019 Nov 5;8(21):e012594. doi: 10.1161/JAHA.119.012594. Epub 2019 Oct 23.

    PubMed 31640455

  • Reardon MJ, Feldman TE, Meduri CU, Makkar RR, O'Hair D, Linke A, Kereiakes DJ, Waksman R, Babliaros V, Stoler RC, Mishkel GJ, Rizik DG, Iyer VS, Gleason TG, Tchetche D, Rovin JD, Lhermusier T, Carrie D, Hodson RW, Allocco DJ, Meredith IT; Reprise III Investigators. Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial. JAMA Cardiol. 2019 Mar 1;4(3):223-229. doi: 10.1001/jamacardio.2019.0091.

    PubMed 30810703

  • Asch FM, Vannan MA, Singh S, Khandheria B, Little SH, Allocco DJ, Meredith IT, Feldman TE, Reardon MJ, Weissman NJ. Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk: An Analysis From the REPRISE III Randomized Controlled Trial. Circulation. 2018 Jun 12;137(24):2557-2567. doi: 10.1161/CIRCULATIONAHA.118.034129. Epub 2018 Mar 12.

    PubMed 29530883

  • Feldman TE, Reardon MJ, Rajagopal V, Makkar RR, Bajwa TK, Kleiman NS, Linke A, Kereiakes DJ, Waksman R, Thourani VH, Stoler RC, Mishkel GJ, Rizik DG, Iyer VS, Gleason TG, Tchetche D, Rovin JD, Buchbinder M, Meredith IT, Gotberg M, Bjursten H, Meduri C, Salinger MH, Allocco DJ, Dawkins KD. Effect of Mechanically Expanded vs Self-Expanding Transcatheter Aortic Valve Replacement on Mortality and Major Adverse Clinical Events in High-Risk Patients With Aortic Stenosis: The REPRISE III Randomized Clinical Trial. JAMA. 2018 Jan 2;319(1):27-37. doi: 10.1001/jama.2017.19132.

    PubMed 29297076

Questions about this trial

What is this clinical trial studying?

A study testing Lotus Valve System, CoreValve/Evolut R Transcatheter Aortic Valve Replacement System and LOTUS Edge Valve System in people with Aortic Stenosis, run by Boston Scientific Corporation at 58 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States, Australia, Canada, France, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Events Included in the Primary Safety Endpoint (time frame: 30 days following procedure). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02202434, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in