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NCT07735130

PHASE4

Angiotensin Receptor Blocker After TAVR in Severe Aortic Stenosis With Left Ventricular Hypertrophy (ARBITAR)

Sponsor: Seoul National University Hospital

View on ClinicalTrials.gov

Summary

This is a multicenter, prospective, open-label, randomized, investigator-initiated trial evaluating whether angiotensin receptor blocker (ARB) therapy improves clinical outcomes in patients with severe aortic stenosis (AS) and left ventricular hypertrophy (LVH) who have undergone transcatheter aortic valve replacement (TAVR). Severe AS imposes chronic pressure overload on the left ventricle, leading to LVH as a compensatory response. While initially adaptive, sustained LVH promotes myocardial fibrosis, reduced ventricular compliance, and impaired cardiac function. LVH that persists after valve replacement is associated with increased morbidity and mortality, including a higher risk of heart failure. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEi) or ARBs has been proposed as a strategy to attenuate adverse left ventricular remodeling after valve replacement by inhibiting angiotensin II-mediated hypertrophic and fibrotic signaling. However, evidence in TAVR patients with LVH remains limited, and a small randomized trial of an ACEi reported drug discontinuation in approximately 10% of patients due to dry cough. The ARBITAR trial therefore evaluates the clinical efficacy of an ARB in this population. A total of 632 patients with symptomatic severe AS and LVH who have successfully undergone TAVR within the prior 30 days will be randomized 1:1 to receive an ARB (experimental group) or no ARB (control group), stratified by site and sex. Assigned treatment is continued for up to 24 months, with follow-up visits at 1, 6, 12, and 24 months. In the experimental group, the ARB (candesartan, losartan, or valsartan) is up-titrated toward a target dose. ACE inhibitors, direct renin inhibitors, and angiotensin receptor/neprilysin inhibitors are prohibited in both groups. The primary endpoint is the composite of all-cause death or admission for heart failure over 2 years. Secondary endpoints include the individual components of the primary endpoint and other clinical events, as well as echocardiographic measures, NT-proBNP, NYHA functional class, and KCCQ-12 score. The primary analysis follows the intention-to-treat principle.

Official title: Angiotensin Receptor Blockade In Patients After Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis With Left Ventricular Hypertrophy (ARBITAR) Trial

Key Details

Gender

All

Age Range

40 Years - Any

Study Type

INTERVENTIONAL

Enrollment

632

Start Date

2026-08-15

Completion Date

2030-06-15

Last Updated

2026-07-29

Healthy Volunteers

Conditions

Transcatheter Aortic Valve Replacement (TAVR)Left Ventricular Hypertrophy Severe Aortic Stenosis

Interventions

DRUG

Angiotensin Receptor Blocker (ARB)

An oral angiotensin receptor blocker - candesartan, losartan, or valsartan - is administered to the experimental group and, as a principle, up-titrated toward the target daily dose, with initiation at a lower starting dose permitted based on clinical need. Doses are: candesartan 4-8 mg once daily titrated to 32 mg once daily; losartan 25-50 mg once daily titrated to 50-150 mg once daily; valsartan 20-40 mg once daily titrated to 160 mg twice daily. Treatment is continued for up to 24 months. Up-titration is considered when all of the following are met: standing systolic blood pressure ≥90 mmHg, no symptoms of hypotension, serum creatinine \<2.0 mg/dL or \<50% increase from baseline, and serum potassium \<5.5 mmol/L. If serum potassium exceeds 6.0 mmol/L, the ARB is discontinued and resumed at a low dose once potassium returns below 5.5 mmol/L.

Inclusion Criteria: * Male or female aged 40 years or older * Symptomatic severe aortic stenosis (AS) with left ventricular hypertrophy (LVH) who successfully underwent transcatheter aortic valve replacement (TAVR) within the prior 30 days, including native-valve or valve-in-valve TAVR \* Severe AS defined by at least one of the following: aortic valve area ≤1.0 cm²; aortic valve area index ≤0.6 cm²/m²; mean pressure gradient ≥40 mmHg; or maximal aortic valve velocity ≥4.0 m/sec \* LVH defined as left ventricular mass index \>115 g/m² in men or \>95 g/m² in women * Successful TAVR (technical success) meeting all VARC-3 criteria: survival; successful access, delivery, and retrieval of the device; correct positioning of a single prosthetic valve in the proper anatomic location; no additional surgery or procedure related to the device (excluding permanent pacemaker implantation) or to major vascular, access-site, or cardiac structural complications; and intended prosthetic valve performance (mean gradient \<20 mmHg, peak velocity \<3 m/s, Doppler velocity index ≥0.25, and less than moderate aortic regurgitation) * Left ventricular ejection fraction (LVEF) \>40% before TAVR * Provided written informed consent to participate, either voluntarily or through a legal representative Exclusion Criteria: * Hypotension (systolic blood pressure \<90 mmHg) or hemodynamic instability defined as a need for continuous intravenous vasopressor support at screening * Hyperkalemia (serum potassium \>5.5 mmol/L) * Bilateral renal artery stenosis without stent placement * Allergy, hypersensitivity, or prior intolerance to angiotensin receptor blockers * Pregnancy, breastfeeding, or planning to become pregnant * Estimated life expectancy of less than 2 years * Acute coronary syndrome diagnosed within the past 1 year * Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2 by the CKD-EPI equation, or currently undergoing renal replacement therapy * Any other medical condition that, in the investigator's judgment, makes participation in the trial inappropriate

Locations (1)

Seoul National University Hospital

Seoul, Seoul, South Korea