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.
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
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
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
Parallel
Angiotensin Receptor Blocker (ARB)
DrugAn 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.
Composite of all-cause death or admission for heart failure
Time to the first occurrence of either all-cause death or admission for heart failure. Admission for heart failure is defined per VARC-3 criteria as hospitalization of at least 24 hours for new or worsening heart failure that is confirmed by signs and symptoms together with diagnostic testing and requires intravenous pharmacologic therapy or mechanical heart failure therapies.
All-cause death
Time to death from any cause after randomization.
Cardiovascular death
Time to death from a cardiovascular cause as defined by VARC-3, including death due to heart failure, cardiogenic shock, prosthetic valve dysfunction, myocardial infarction, stroke, thromboembolism, bleeding, cardiac tamponade, vascular complication, arrhythmia or conduction disorder, or cardiovascular infection, as well as intraprocedural death, sudden death, and death of undetermined cause.
Any admission
Time to first hospitalization for any cause after randomization.
Admission for heart failure
Time to first hospitalization for new or worsening heart failure, defined per VARC-3 as an admission of at least 24 hours confirmed by signs and symptoms together with diagnostic testing and requiring intravenous pharmacologic therapy or mechanical heart failure therapies.
Echocardiographic measurements - LVEF
Left ventricular ejection fraction measured by transthoracic echocardiography, assessed serially over the follow-up period. Unit of Measure: percentage (%)
Echocardiographic measurement - Peak aortic velocity
Peak aortic jet velocity measured by transthoracic echocardiography, assessed serially over the follow-up period. Unit of Measure: m/s
Echocardiographic measurement - Peak transaortic gradient
Peak transaortic pressure gradient measured by transthoracic echocardiography, assessed serially over the follow-up period. Unit of Measure: mmHg
Echocardiographic measurement - Mean transaortic gradient
Mean transaortic pressure gradient measured by transthoracic echocardiography, assessed serially over the follow-up period. Unit of Measure: mmHg
Click on the lead sponsor to view all of their trials.
Seoul National University Hospital
Lead sponsor
Samjin Pharmaceutical Co., Ltd.
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
