RHEIA (Randomized researcH in womEn All Comers With Aortic Stenosis)

NCT04160130 | Unknown DMC

• 2 other identifiers: RHEIACIV-19-11-030544
• Study Type: interventional
• Target: 432
• Locations: 12 countries
• Sites: 48

Brief Summary

Purpose of this prospective, randomized, controlled, multi-center study is to evaluate the safety and efficacy of Transcatheter Aortic Valve Implantation (TAVI) as compared to surgical aortic valve replacement (SAVR) in female patients with severe symptomatic aortic stenosis. Patients will be randomized 1:1 to receive either TAVI or SAVR aortic valve replacement. For TAVI procedure, Edwards SAPIEN 3 THV system Model 9600 TFX (20, 23, 26 and 29 mm) or SAPIEN 3 Ultra THV system Model 9750 TFX (20, 23, 26) with the associated transfemoral delivery systems will be sued, for SAVR any commercially available surgical bioprosthetic valve. Patients will undergo the following visits: Screening, Procedure, Post Procedure, Discharge, 30 day, 6 months (telephone contact) and 1 year.

Conditions

Aortic Valve Stenosis; Heart Valve Diseases

Keywords

Research in woman; Transcatheter Aortic Valve Implantation (TAVI); surgical aortic valve replacement (SAVR); cardiovascular disease; heart disease; Sapien 3; Transcatheter Aortic Valve Replacement (TAVR)

Outcome Measures

Primary Outcomes (3)

• Mortality

  Number of patients with death of any cause (death due to proximate cardiac cause, death caused by non-coronary vascular conditions, procedure-related deaths, valve-related deaths, sudden or unwitnessed death, non-cardiovascular mortality, death of unknown cause)

  through study completion, an average of 1 year

• Stroke

  Number of patients with stroke (disabling and non-disabling).

  through study completion, an average of 1 year

• Re-hospitalization

  Number of patients with re-hospitalization (valve-related or procedure-related or worsening of congestive heart failure).

  through study completion, an average of 1 year

Secondary Outcomes (17)

• Length of Index hospitalization

  through day of procedure until day of discharge

• Prosthesis-patient mismatch

  up to 30 days post-procedure

• New onset atrial fibrillation

  through study completion, an average of 1 year

• Vascular complications

  through study completion, an average of 1 year

• Bleeding complications

  through study completion, an average of 1 year

Study Arms (2)

SAPIEN 3 or SAPIEN 3 Ultra

EXPERIMENTAL

Edwards SAPIEN 3 THV system Model 9600 TFX (20, 23, 26 and 29 mm) or SAPIEN 3 Ultra THV system Model 9750 TFX (20, 23, 26) with the associated transfemoral delivery systems.

Procedure: Transcatheter aortic valve replacement

any surgical bioprosthetic aortic valve

ACTIVE COMPARATOR

Any commercially available surgical bioprosthetic valve

Procedure: Transcatheter aortic valve replacement

Interventions

Transcatheter aortic valve replacement PROCEDURE

Patients will be randomized 1:1 to receive either transcatheter aortic valve replacement (TAVI) or aortic valve replacement with a commercially available surgical bioprosthetic valve.

Also known as: Surgical aortic valve replacement

SAPIEN 3 or SAPIEN 3 Ultra; any surgical bioprosthetic aortic valve

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients with severe aortic stenosis as follows:
• High gradient severe AS (Class I Indication for aortic valve replacement \[AVR\]): Jet velocity ≥ 4.0 m/s or mean gradient ≥ 40 mmHg with Aortic Valve Area (AVA) ≤ 1.0 cm\^2 or AVA index ≤ 0.6 cm\^2/m\^2 OR
• Low gradient severe aortic stenosis (Class I/IIa indication of AVR) Jet velocity \< 4.0 m/s and mean gradient \< 40 mmHg and AVA ≤ 1.0 cm\^2 and AVA index ≤ 0.6 cm\^2/m\^2 with confirmation of severe AS by: mean gradient ≥40 mmHg on dobutamine stress echocardiography and/or aortic valve calcium score ≥ 1200 AU on non-contrast CT.
• AND
• NYHA Functional Class ≥ II OR
• Exercise test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia
• Age ≥ 18 years
• The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB)/Ethics Committee (EC) of the respective clinical site.

You may not qualify if:

• Patient is not a candidate for both surgical and transcatheter aortic valve replacement.
• Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV based on 3D imaging analysis
• Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
• Evidence of an acute myocardial infarction ≤ 1 month (30 days) before randomization
• Aortic valve is unicuspid, bicuspid, or is non-calcified
• Severe aortic regurgitation (\>3+)
• Any concomitant valve disease that requires an intervention
• Complex coronary artery disease:
• Unprotected left main coronary artery stenosis
• Syntax score \> 32 (in the absence of prior revascularization)
• Heart Team assessment that optimal revascularization cannot be performed.
• Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days before randomization
• Leukopenia (WBC \< 3000 cell/mcL), anemia (Hgb \< 9 g/dL), Thrombocytopenia (Plt \< 50,000 cell/mcL), history of bleeding diathesis or coagulopathy, or hypercoagulable states
• Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days before randomization
• Hypertrophic cardiomyopathy with obstruction

Sponsors & Collaborators

• Optimapharm: lead
• Edwards Lifesciences: collaborator

Study Sites (48)

LKH-Univ. Klinikum Graz

Graz, 8036, Austria

Location

Universitätskliniken Innsbruck

Innsbruck, 6020, Austria

Location

Universitätsklinikum St. Pölten - Lilienfeld

Sankt Pölten, 3100, Austria

Location

Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

Clinique Saint-Luc

Bouge, 5004, Belgium

Location

CHU De Charleroi

Charleroi, 6140, Belgium

Location

UZ Leuven Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Nicosia General Hospital

Nicosia, 1450, Cyprus

Location

University hospital Hradec Králové

Hradec Králové, 50005, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 77900, Czechia

Location

IKEM (Institut Klinické a Experimentální Medicíny)

Prague, 140 21, Czechia

Location

Nemocnice Na Homolce

Prague, 150 30, Czechia

Location

Helsinky University Hospital

Helsinki, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

CHU de Bordeaux - Hôpital cardiologique du Haut-Lévêqu

Bordeaux, 33600, France

Location

CHRU de Brest

Brest, 29200, France

Location

GHE-Hôpital Cardiologique Louis Pradel

Bron, 69677, France

Location

CHU Clermont-Ferrand - Hôpital Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

CHU Dijon

Dijon, 21000, France

Location

CHU Lille - Institute Coeur Poumon

Lille, 59037, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

CHU de Nantes - Hôpital Guillaume et René Laënnec

Nantes, 44093, France

Location

Hôpital Privé Jacques Cartier

Paris, 91300, France

Location

CHU et Université de Poitiers

Poitiers, 86000, France

Location

CHU Rennes - Hopital de Pontchaillou

Rennes, 35000, France

Location

CHU Rouen - Hopital Charles Nicolle

Rouen, 76000, France

Location

Les Hopitaux Universitaires de Strasbourg - Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

Clinique Pasteur

Toulouse, 31076, France

Location

Universitätsklinik der Ruhr-Universität Bochum

Bad Oeynhausen, 32545, Germany

Location

Deutsches Herzzentrum Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Frankfurt Am Main

Frankfurt, 60590, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

St. James´s Hospital

Dublin, Ireland

Location

Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"

Catania, 95123, Italy

Location

A.O.U. Careggi

Florence, 50134, Italy

Location

Ospedale del Cuore G. Pasquinucci

Massa, Italy

Location

Universita di Padova

Padua, Italy

Location

European Hospital

Roma, 00149, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Italy

Location

Catharina Ziekenhuis Eindhoven

Eindhoven, 5623 EJ, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333, Netherlands

Location

St Antonius Ziekenhuis Nieuwegein

Nieuwegein, 3445 CM, Netherlands

Location

Inselspital Universitätsspital Bern

Bern, 3010, Switzerland

Location

Hirslanden Klinik Im Park

Zurich, 8027, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

Morriston Hospital

Morriston, SA6 6NL, United Kingdom

Location

Oxford University Hospitals - John Radcliffe hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (3)

• Silva I, Alperi A, Hecht S, Zanuttini A, Theron A, Giuliani C, Camacho B, Dahou A, Mares J, Bax J, Bonaros N, Windecker S, Messika-Zeitoun D, Wesselink W, Rakova R, Bramlage P, Tchetche D, Eltchaninoff H, Pibarot P; RHEIA Trial Investigators. Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Women With Severe Aortic Stenosis: The RHEIA Trial. J Am Heart Assoc. 2026 Jan 6;15(1):e047196. doi: 10.1161/JAHA.125.047196. Epub 2025 Dec 30.

  PMID: 41467363 DERIVED

• Tchetche D, Pibarot P, Bax JJ, Bonaros N, Windecker S, Dumonteil N, Nietlispach F, Messika-Zeitoun D, Pocock SJ, Berthoumieu P, Swaans MJ, Timmers L, Rudolph TK, Bleiziffer S, Leroux L, Modine T, van der Kley F, Auffret V, Tomasi J, Stastny L, Hengstenberg C, Andreas M, Leclercq F, Gandet T, Mascherbauer J, Trescher K, Prendergast B, Vasa-Nicotera M, Chieffo A, Mares J, Wesselink W, Rakova R, Kurucova J, Bramlage P, Eltchaninoff H. Transcatheter vs. surgical aortic valve replacement in women: the RHEIA trial. Eur Heart J. 2025 Jun 9;46(22):2079-2088. doi: 10.1093/eurheartj/ehaf133.

  PMID: 40171878 DERIVED

• Eltchaninoff H, Bonaros N, Prendergast B, Nietlispach F, Vasa-Nicotera M, Chieffo A, Pibarot P, Bramlage P, Sykorova L, Kurucova J, Bax JJ, Windecker S, Dumonteil N, Tchetche D. Rationale and design of a prospective, randomized, controlled, multicenter study to evaluate the safety and efficacy of transcatheter heart valve replacement in female patients with severe symptomatic aortic stenosis requiring aortic valve intervention (Randomized researcH in womEn all comers wIth Aortic stenosis [RHEIA] trial). Am Heart J. 2020 Oct;228:27-35. doi: 10.1016/j.ahj.2020.06.016. Epub 2020 Jun 30.

  PMID: 32745733 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis; Heart Valve Diseases; Cardiovascular Diseases; Heart Diseases

Interventions

Transcatheter Aortic Valve Replacement

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Heart Valve Prosthesis Implantation; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Prosthesis Implantation; Thoracic Surgical Procedures

Study Officials

• Hélène Eltchaninoff, Prof.

  CHU Rouen - Hopital Charles Nicolle

  PRINCIPAL INVESTIGATOR

• Didier Tchétché, Dr.

  Clinique Pasteur Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 12, 2019
• Study Start: November 29, 2019
• Primary Completion: February 1, 2024
• Study Completion: June 1, 2024
• Last Updated: June 1, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2); IT (6); NL (3); IE (1); GB (3); CY (1); BE (3); CZ (4); FR (14); CH (3); AU (4); DE (4)