Aortic StenosisPhase 3REVERSE-TAVRNCT07090343
Semaglutide in Patients Undergoing Transcatether Aortic Valve Replacement
A Phase 3 study testing Wegovy ® in people with Aortic Stenosis and Heart Failure, run by Leiden University Medical Center.
Trial summary
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial evaluating the safety and efficacy of once-weekly semaglutide 2.4 mg in adult patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) who meet current clinical criteria for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis, Heart Failure
- What is being tested?
- Wegovy ®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 826 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2026to 1 Apr 2031
- Phase
- Phase 3
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Treatment with an GLP-1 receptor agonist within the previous 90 days.
- Myocardial infarction, stroke, hospitalization for unstable angina or transient ischemic attack within the previous 60 days.
- Planned coronary, carotid or peripheral artery revascularization known on the day of screening.
- eGFR <25 mL/min/1.73 m² or intermittent hemodialysis or peritoneal dialysis.
- Presence of acute pancreatitis within the last 180 days prior to screening.
- History or presence of chronic pancreatitis.
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- Self-reported change in body weight of >5 kg within 90 days before screening.
- Bariatric surgery prior to screening or planned bariatric surgery within the trial time course.
- Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell cancer and any carcinoma in-situ are allowed.
- Known or suspected hypersensitivity to trial product(s) or related products.
- Participation in any clinical trial of an approved or non-approved device for the treatment of aortic stenosis or obesity within 30 days before screening.
- Receipt of any investigational medicinal product within 30 days before screening.
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
- Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Semaglutide for Reducing Cardiovascular Events in Patients Undergoing Transcatether Aortic Valve Replacement
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial evaluating the safety and efficacy of once-weekly semaglutide 2.4 mg in adult patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) who meet current clinical criteria for semaglutide treatment. A total of 826 participants will be randomized 1:1 to receive semaglutide or placebo as an add-on to standard-of-care, starting 3 months before TAVR and continuing for 24 months post-procedure. The primary endpoint is time to first occurrence of a composite of cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke or transient ischemic accident (TIA), and hospitalization for heart failure (HF). The study is event-driven and powered to detect a 20% relative risk reduction in primary outcome events. This trial aims to address the unmet need for medical therapies that improve outcomes in patients with severe AS following TAVR, with potential for direct clinical implementation.
- Conditions
- Aortic Stenosis, Heart Failure
- Being tested
- Wegovy ®, Placebo
- Medical subject headings
- Aortic Valve Stenosis, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Wegovy ®Drug
Semaglutide 2.4 mg subcutaneous once-weekly starting 3 months prior TAVR and continued 24 months post-TAVR. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose as an add-on to standard-of-care. The treatment will continue until the 'end of treatment' visit followed by a 8 weeks follow-up period.
PlaceboDrug
Matching placebo subcutaneous once-weekly.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Active comparator | Not described Receives: Drug: Wegovy ® |
| Control Arm | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF
From randomization to first occurrence of a composite endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF.
Measured: From randomization through 12 and 27 months
Secondary outcomes (14)
Incidence rate of each component of the primary outcome.
Measured: From randomization at 12 months and 27 months
Change in high sensitivity C-Reactive Protein (hsCRP) (mg/L)
Measured: From randomization at 12 and 27 months
A 5-component composite nephropathy endpoint consisting of: onset of persistent macroalbuminuria, persistent 50% reduction in eGFR compared with baseline (randomization), onset of persistent eGFR < 15 ml/min/1.73m2, initiation of chronic renal replacemen
Measured: From randomization at 12 and 27 months
Change in Lipid Profile (mg/dL)
Measured: From randomization at 12 and 27 months
Change in waist circumference
Measured: From randomization at 12 and 27 months
Change in HbA1c (%, mmol /mol)
Measured: From randomization at 12 and 27 months
Change in systolic blood pressure
Measured: From randomization at 12 and 27 months
Changes in LV remodeling (echocardiographic assessment of LV size, mass, systolic and diastolic function)
Measured: From randomization at 12 and 27 months
Change in loop diuretic medication
Measured: From randomization at 12 and 27 months
Change in H2FPEF score
Change in H2FPEF score scale
Measured: From randomization at 12 and 27 months
Change in NT-proBNP
Measured: From randomization at 12 and 27 months
Change in KCCQ score
Change in the KCCQ score scale
Measured: From randomization at 12 and 27 months.
Subject experiencing deterioration in NYHA functional class
Subject experiencing deterioration in NYHA functional class
Measured: From randomization at 12 and 27 months
Change in body weight (%)
Change in body weight from randomization.
Measured: From randomization at 12 and 27 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study start1 Apr 2026 (estimated)
- Primary completion1 Sep 2030 (estimated)
- Study completion1 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aortic 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a Phase III, randomized, placebo-controlled, double-blinded, multi-center clinical trial conducted at five centers in the Netherlands, comparing semaglutide 2.4 mg with placebo both administered subcutaneous (sc) once-weekly in subjects with severe AS undergoing TAVR with obesity or overweight and CV risk factors. Eligible subjects will be randomized in a 1:1 manner to receive either semaglutide sc. 2.4 mg or placebo once-weekly as an add-on to standard-of-care. Interventions: * Treatment Arm: Semaglutide 2.4 mg subcutaneous once-weekly starting 3 months prior TAVR and continued 24 months post-TAVR. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose as an add-on to standard-of-care. The treatment will continue until the 'end of treatment' visit followed by a 8 weeks follow-up period. * Control Arm: Matching placebo subcutaneous once-weekly.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 826 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nina Ajmone Marsan, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07090343
- Sponsor's protocol ID
- REVERSE-TAVR
- Acronym
- REVERSE-TAVR
- Status last verified
- Jul 2025
- First submitted
- 11 Jul 2025
- Last updated
- 29 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.
PubMed 27633186Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30.
PubMed 39222642