Aortic Valve StenosisRHEIANCT04160130
RHEIA (Randomized researcH in womEn All Comers With Aortic Stenosis)
A study testing Transcatheter aortic valve replacement in people with Aortic Valve Stenosis and Heart Valve Diseases, run by Optimapharm at 48 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Aortic Valve Stenosis, Heart Valve Diseases
- What is being tested?
- Transcatheter aortic valve replacement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 432 participants
- Where
- 48 sitesin 12 countries
- Study dates
- 29 Nov 2019to Jun 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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+)
Show all 34Show fewer
- Any concomitant valve disease that requires an intervention
- Pre-existing mechanical or bioprosthetic valve in any position (mitral ring is not an exclusion).
- 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
- Ventricular dysfunction with lleft ventricular ejection fraction < 30%
- Cardiac imaging (echo, CT, and/or MRI) evidence of intracardiac mass, thrombus or vegetation
- Inability to tolerate or condition precluding treatment with anti- thrombotic/anticoagulation therapy during or after the valve implant procedure
- Stroke or transient ischemic attack within 90 days before randomization
- Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy
- Active bacterial endocarditis within 180 days of randomization
- Severe lung disease (FEV1 < 50%) or currently on home oxygen
- Severe pulmonary hypertension (e.g., pulmonary arterial systolic pressure ≥ 2/3 systemic pressure)
- History of cirrhosis or any active liver disease
- Significant abdominal or thoracic aortic disease (such as porcelain aorta, aneurysm, severe calcification, aortic coarctation, etc.) that would preclude safe passage of the delivery system or cannulation and aortotomy for surgical AVR.
- Hostile chest or conditions or complications from prior surgery that preclude safe reoperation (e.g., mediastinitis, radiation damage, abnormal chest wall, adhesion of aorta or internal mammary artery to sternum, etc.)
- Patient refuses blood products
- BMI > 50 kg/m^2
- Estimated life expectancy < 24 months
- Absolute contraindications or allergy to iodinated contrast agent that cannot be adequately treated with pre-medication
- Immobility that would prevent completion of study procedures
- Currently participating in an investigational drug or another device study.
- Pregnancy or lactation
Trial locations and contacts
48 sites in 12 countries.
48 sites in 12 countries
France14 sites
CHU de Bordeaux - Hôpital cardiologique du Haut-Lévêqu
Bordeaux, 33600
CHRU de Brest
Brest, 29200
GHE-Hôpital Cardiologique Louis Pradel
Bron, 69677
CHU Clermont-Ferrand - Hôpital Gabriel Montpied
Clermont-Ferrand, 63000
CHU Dijon
Dijon, 21000
CHU Lille - Institute Coeur Poumon
Lille, 59037
CHU Montpellier
Montpellier, 34295
CHU de Nantes - Hôpital Guillaume et René Laënnec
Nantes, 44093
Hôpital Privé Jacques Cartier
Paris, 91300
CHU et Université de Poitiers
Poitiers, 86000
CHU Rennes - Hopital de Pontchaillou
Rennes, 35000
CHU Rouen - Hopital Charles Nicolle
Rouen, 76000
Les Hopitaux Universitaires de Strasbourg - Nouvel Hôpital Civil
Strasbourg, 67091
Clinique Pasteur
Toulouse, 31076
Italy6 sites
Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"
Catania, 95123
A.O.U. Careggi
Florence, 50134
Ospedale del Cuore G. Pasquinucci
Massa
Universita di Padova
Padova
European Hospital
Roma, 00149
Azienda Ospedaliera Universitaria Integrata Verona
Verona
Austria4 sites
LKH-Univ. Klinikum Graz
Graz, 8036
Universitätskliniken Innsbruck
Innsbruck, 6020
Universitätsklinikum St. Pölten - Lilienfeld
Sankt Pölten, 3100
Allgemeines Krankenhaus der Stadt Wien
Vienna, 1090
Czechia4 sites
University hospital Hradec Králové
Hradec Králové, 50005
Fakultni nemocnice Olomouc
Olomouc, 77900
IKEM (Institut Klinické a Experimentální Medicíny)
Prague, 140 21
Nemocnice Na Homolce
Prague, 150 30
Germany4 sites
Universitätsklinik der Ruhr-Universität Bochum
Bad Oeynhausen, 32545
Deutsches Herzzentrum Berlin
Berlin, 13353
Universitätsklinikum Frankfurt Am Main
Frankfurt, 60590
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
Belgium3 sites
Clinique Saint-Luc
Bouge, 5004
CHU De Charleroi
Charleroi, 6140
UZ Leuven Campus Gasthuisberg
Leuven, 3000
Netherlands3 sites
Catharina Ziekenhuis Eindhoven
Eindhoven, 5623 EJ
Leids Universitair Medisch Centrum
Leiden, 2333
St Antonius Ziekenhuis Nieuwegein
Nieuwegein, 3445 CM
Switzerland3 sites
Inselspital Universitätsspital Bern
Bern, 3010
Hirslanden Klinik Im Park
Zurich, 8027
Universitätsspital Zürich
Zurich, 8091
United Kingdom3 sites
Royal Infirmary of Edinburgh
Edinburgh
Morriston Hospital
Morriston, SA6 6NL
Oxford University Hospitals - John Radcliffe hospital
Oxford, OX3 9DU
Finland2 sites
Helsinky University Hospital
Helsinki
Tampere University Hospital
Tampere
About this study
Official title: A Prospective, Randomized, Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Transcatheter Aortic Valve Implantation in Female Patients Who Have Severe Symptomatic Aortic Stenosis Requiring Aortic Valve Replacement
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.
Read the detailed description
Recent large meta-analyses and a large retrospective study from the STS/ACC TVT Registry demonstrated improved survival in female versus male aortic sclerosis patients undergoing TAVI despite their advanced age and increased rates of major peri-procedural vascular complications, bleeding events and strokes. These gender-related patient profile differences have also been present in multicentre cohorts across the world. A recent meta-analysis by Siontis et al. showed that TAVI, when compared with SAVR, was associated with a significant 13% relative risk reduction in 2-year mortality, a benefit more pronounced amongst females and patients undergoing transfemoral TAVI.
In a recent meta-analysis, the female-specific survival advantage from TAVI over SAVR was explored. Amongst females, TAVI recipients had a significantly lower mortality than SAVR recipients, at 1 year (OR 0.68; 95%CI 0.50 to 0.94). Amongst males there was no difference in mortality between TAVI and SAVR at 1 year (OR 1.09; 95%CI 0.86 to 1.39). There was statistically significant evidence of a difference in treatment effect between genders at 1 year (p interaction = 0.02). In an attempt to explore the mechanisms for an increased mortality rate in women undergoing SAVR, different endpoints were explored in female patients exclusively. It was shown that women, undergoing SAVR, having both a higher periprocedural mortality, higher rates of bleeding and acute kidney injury, worse patient prosthesis match and worse long term recovery of left ventricular function.In the recent PARTNER 3 the composite of death from any cause, stroke, or rehospitalization had occurred in 42 patients (8.5%) in the TAVI group as compared with 68 patients (15.1%) in the surgery group at 1 year. The difference was 6.6% (95%CI -10.8% to -2.3%) and thus exceeded the pre-defined non-inferiority margin of 6%.
Subgroup analyses of the primary end point at 1 year showed no heterogeneity of treatment effect in any of the subgroups that were examined including gender (p=0.27). There were 292 women included with an endpoint rate of 18.5% for SAVR (men 13.8%) and 8.1% for TAVI (men 8.7%), showing a clear trend for an increased benefit of women undergoing TAVI instead of SAVR (rate difference -10.4%; 95%CI -18.3% to -2.5%). Nonetheless, the benefits of TAVI were preserved in both men and women.Earlier observational and clinical studies indicated an increased risk for women undergoing SAVR compared to men while being at a comparable risk for TAVI. In a recent meta-analysis of TAVI vs. SAVR in men and women the risk of dying from the intervention was reduced by a relative 32% in women (OR 0.38; 95%CI 0.50-0.94) while there was no such difference in men (OR 1.09; 95%CI 0.86-1.39). This was mostly documented as being the effect of a reduced periprocedural mortality with TAVI (-54%; OR 0.46; 95%CI 0.22-0.96) and major bleeding (-57%; OR 0.43; 95%CI 0.25-0.73) while the difference in strokes and acute kidney injury did not reach statistical significance. Taken all available scientific data on the comparison of TAVI versus open surgery in patients with indication for AVR together it remains probable, that independently of the individual surgical risk female patients in particular seem to benefit from a non-surgical aortic valve replacement strategy.
As the indirect comparisons of the intermediate to low risk outcomes in PARTNER 2/3 suggest a favorable risk reduction in women compared to men as described, the investigators believe it is timely for a dedicated trial to demonstrate the non-inferiority of TAVI in women compared to SAVR and, in case of this being true, whether TAVI is actually superior to performing SAVR.
- Conditions
- Aortic Valve Stenosis, Heart Valve Diseases
- Being tested
- Transcatheter aortic valve replacement
- 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)
- Medical subject headings
- Aortic Valve Stenosis, Heart Valve Diseases, Cardiovascular Diseases, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcatheter aortic valve replacementProcedure or surgery
Also called Surgical aortic valve replacement
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Transcatheter aortic valve replacement |
| any surgical bioprosthetic aortic valve | Active comparator | Any commercially available surgical bioprosthetic valve Receives: Procedure: Transcatheter aortic valve replacement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: through study completion, an average of 1 year
Stroke
Number of patients with stroke (disabling and non-disabling).
Measured: 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).
Measured: through study completion, an average of 1 year
Secondary outcomes (17)
Length of Index hospitalization
Number of days per patient for index hospitalization.
Measured: through day of procedure until day of discharge
Prosthesis-patient mismatch
Number of patients with a prosthesis mismatch.
Measured: up to 30 days post-procedure
New onset atrial fibrillation
Number of patients with a new onset of atrial fibrillation.
Measured: through study completion, an average of 1 year
Vascular complications
Number of patients with major vascular complications.
Measured: through study completion, an average of 1 year
Bleeding complications
Number of patients with life-threatening, disabling, or major bleeding complications.
Measured: through study completion, an average of 1 year
Myocardial infarction
Number of patients with new myocardial infarction.
Measured: through study completion, an average of 1 year
Acute kidney injury
Number of patients with new onset of acute kidney injury stage II/III (AKIN classification).
Measured: up to 30 days post-procedure
Acute kidney injury
Number of patients with the need of renal replacement therapy.
Measured: through study completion, an average of 1 year
New permanent pacemaker implantation
Number of patients with new permanent pacemaker implantation caused by new or worsened conduction disturbances.
Measured: through study completion, an average of 1 year
Change in New York Heart Association (NYHA) classification
Severity of cardiac disease based on functional capacity will be described using the NYHA classification. Classification ranges from I - IV, with the lowest (I) as no limitations and the highest (IV) unable to carry on any physical activity.
Measured: through study completion, an average of 1 year
Change in hemodynamic valve performance
Hemodynamic valve performance will be evaluated by echocardiography for aortic valve stenosis and aortic valve regurgitation (paravalvular \& central).
Measured: through study completion, an average of 1 year
Change in impairment caused by a stroke
Impairment caused by a stroke will be assessed using the the National Institutes of Health Stroke Scale (NIHSS)
Measured: through study completion, an average of 1 year
Change in cognitive function
Cognitive function will be assessed using the Mini-mental state Examination-2 (MMSE-2) questionnaire
Measured: through study completion, an average of 1 year
Change in the degree of disability in the daily activities
Degree of disability in the daily activities will be assessed using the modified Rankin Scale (mRS).
Measured: through study completion, an average of 1 year
Change in Frailty Index
Frailty index will be assessed by the 5 Meter Walk Test, grip strength, Instrumental Activities of Daily Living and serum Albumin
Measured: through study completion, an average of 1 year
Change in disease-specific health status
The health status in regards to congestive heart failure will be assessed by the patient using the Kansas City Cardiomyopathy Questionnaire (KCCQ).
Measured: through study completion, an average of 1 year
Change in health-related quality of life
The health-related Quality of Life will be assessed by the patient using The Medical Outcomes Study Short-Form 12 (SF-12) questionnaire.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start29 Nov 2019
- Primary completionFeb 2024 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve StenosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 432 participants (actual)
Sponsor and investigators
- Lead sponsor
- Optimapharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Edwards Lifesciences
- Responsible party
- Sponsor
- Investigators
- Hélène Eltchaninoff, Prof., Principal investigator, CHU Rouen - Hopital Charles NicolleDidier Tchétché, Dr., Principal investigator, Clinique Pasteur Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04160130
- Sponsor's protocol ID
- RHEIA
- Other IDs
- CIV-19-11-030544
- Acronym
- RHEIA
- Status last verified
- May 2023
- First submitted
- 6 Nov 2019
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41467363Tchetche 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.
PubMed 40171878Eltchaninoff 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.
PubMed 32745733
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Transcatheter Aortic Valve Implantation in Female Patients Who Have Severe Symptomatic Aortic Stenosis Requiring Aortic Valve Replacement
- ClinicalTrials.gov ID
- NCT04160130
- Acronym / sponsor ID
- RHEIA / RHEIA
- 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)
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 432 participants (actual)
- Lead sponsor
- OptimapharmIndustry (pharma, biotech, devices)
- Collaborators
- Edwards Lifesciences
- Study start
- 29 Nov 2019 (actual)
- Primary completion
- Feb 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Recent large meta-analyses and a large retrospective study from the STS/ACC TVT Registry demonstrated improved survival in female versus male aortic sclerosis patients undergoing TAVI despite their advanced age and increased rates of major peri-procedural vascular complications, bleeding events and strokes. These gender-related patient profile differences have also been present in multicentre cohorts across the world. A recent meta-analysis by Siontis et al. showed that TAVI, when compared with SAVR, was associated with a significant 13% relative risk reduction in 2-year mortality, a benefit more pronounced amongst females and patients undergoing transfemoral TAVI.
In a recent meta-analysis, the female-specific survival advantage from TAVI over SAVR was explored. Amongst females, TAVI recipients had a significantly lower mortality than SAVR recipients, at 1 year (OR 0.68; 95%CI 0.50 to 0.94). Amongst males there was no difference in mortality between TAVI and SAVR at 1 year (OR 1.09; 95%CI 0.86 to 1.39). There was statistically significant evidence of a difference in treatment effect between genders at 1 year (p interaction = 0.02). In an attempt to explore the mechanisms for an increased mortality rate in women undergoing SAVR, different endpoints were explored in female patients exclusively. It was shown that women, undergoing SAVR, having both a higher periprocedural mortality, higher rates of bleeding and acute kidney injury, worse patient prosthesis match and worse long term recovery of left ventricular function.In the recent PARTNER 3 the composite of death from any cause, stroke, or rehospitalization had occurred in 42 patients (8.5%) in the TAVI group as compared with 68 patients (15.1%) in the surgery group at 1 year. The difference was 6.6% (95%CI -10.8% to -2.3%) and thus exceeded the pre-defined non-inferiority margin of 6%.
Subgroup analyses of the primary end point at 1 year showed no heterogeneity of treatment effect in any of the subgroups that were examined including gender (p=0.27). There were 292 women included with an endpoint rate of 18.5% for SAVR (men 13.8%) and 8.1% for TAVI (men 8.7%), showing a clear trend for an increased benefit of women undergoing TAVI instead of SAVR (rate difference -10.4%; 95%CI -18.3% to -2.5%). Nonetheless, the benefits of TAVI were preserved in both men and women.Earlier observational and clinical studies indicated an increased risk for women undergoing SAVR compared to men while being at a comparable risk for TAVI. In a recent meta-analysis of TAVI vs. SAVR in men and women the risk of dying from the intervention was reduced by a relative 32% in women (OR 0.38; 95%CI 0.50-0.94) while there was no such difference in men (OR 1.09; 95%CI 0.86-1.39). This was mostly documented as being the effect of a reduced periprocedural mortality with TAVI (-54%; OR 0.46; 95%CI 0.22-0.96) and major bleeding (-57%; OR 0.43; 95%CI 0.25-0.73) while the difference in strokes and acute kidney injury did not reach statistical significance. Taken all available scientific data on the comparison of TAVI versus open surgery in patients with indication for AVR together it remains probable, that independently of the individual surgical risk female patients in particular seem to benefit from a non-surgical aortic valve replacement strategy.
As the indirect comparisons of the intermediate to low risk outcomes in PARTNER 2/3 suggest a favorable risk reduction in women compared to men as described, the investigators believe it is timely for a dedicated trial to demonstrate the non-inferiority of TAVI in women compared to SAVR and, in case of this being true, whether TAVI is actually superior to performing SAVR.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SAPIEN 3 or SAPIEN 3 Ultra | Experimental | Procedure: Transcatheter aortic valve replacementEdwards 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. |
| any surgical bioprosthetic aortic valve | Active comparator | Procedure: Transcatheter aortic valve replacementAny commercially available surgical bioprosthetic valve |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female patients with severe aortic stenosis as follows:
- AND
- 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.
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcatheter aortic valve replacementAlso: Surgical aortic valve replacementPatients will be randomized 1:1 to receive either transcatheter aortic valve replacement (TAVI) or aortic valve replacement with a commercially available surgical bioprosthetic valve. | Procedure or surgery | SAPIEN 3 or SAPIEN 3 Ultra, any surgical bioprosthetic aortic valve |
Primary outcome
Mortality
Time frame: through study completion, an average of 1 year
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)
Stroke
Time frame: through study completion, an average of 1 year
Number of patients with stroke (disabling and non-disabling).
Re-hospitalization
Time frame: through study completion, an average of 1 year
Number of patients with re-hospitalization (valve-related or procedure-related or worsening of congestive heart failure).
17 secondary outcomes
Length of Index hospitalization
Time frame: through day of procedure until day of discharge
Prosthesis-patient mismatch
Time frame: up to 30 days post-procedure
New onset atrial fibrillation
Time frame: through study completion, an average of 1 year
Vascular complications
Time frame: through study completion, an average of 1 year
Bleeding complications
Time frame: through study completion, an average of 1 year
Myocardial infarction
Time frame: through study completion, an average of 1 year
Acute kidney injury
Time frame: up to 30 days post-procedure
Acute kidney injury
Time frame: through study completion, an average of 1 year
New permanent pacemaker implantation
Time frame: through study completion, an average of 1 year
Change in New York Heart Association (NYHA) classification
Time frame: through study completion, an average of 1 year
Change in hemodynamic valve performance
Time frame: through study completion, an average of 1 year
Change in impairment caused by a stroke
Time frame: through study completion, an average of 1 year
Change in cognitive function
Time frame: through study completion, an average of 1 year
Change in the degree of disability in the daily activities
Time frame: through study completion, an average of 1 year
Change in Frailty Index
Time frame: through study completion, an average of 1 year
Change in disease-specific health status
Time frame: through study completion, an average of 1 year
Change in health-related quality of life
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
- Derived from this study: PubMed 41467363Silva 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.
- Derived from this study: PubMed 40171878Tchetche 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.
- Derived from this study: PubMed 32745733Eltchaninoff 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hélène Eltchaninoff, Prof. principal investigator
CHU Rouen - Hopital Charles Nicolle
Didier Tchétché, Dr. principal investigator
Clinique Pasteur Toulouse
48 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcatheter aortic valve replacement in people with Aortic Valve Stenosis and Heart Valve Diseases, run by Optimapharm at 48 sites in 12 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 8 inclusion and 34 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: status not confirmed, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in France, Italy, Austria, Czechia, Germany and 7 more countries. 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?
Results are not available in the source record.
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?
Mortality (time frame: through study completion, an average of 1 year). The study lists 3 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 NCT04160130, which also lists 3 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 1 Jun 2023.