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

NCT07735130 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: H-2601-159-1713
• Study Type: interventional
• Target: 632
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Severe aortic stenosis; Renin-angiotensin system blockade; Angiotensin receptor blocker; Transcatheter aortic valve replacement (TAVR); Left ventricular hypertrophy

Outcome Measures

Primary Outcomes (1)

• 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.

  From randomization to 2 years

Secondary Outcomes (7)

• All-cause death

  From randomization to 2 years

• Cardiovascular death

  From randomization to 2 years

• Any admission

  From randomization to 2 years

• Admission for heart failure

  From randomization to 2 years

• Myocardial infarction

  From randomization to 2 years

Other Outcomes (18)

• Echocardiographic measurements - LVEF

  Baseline and 1, 6, 12, and 24 months

• Echocardiographic measurement - Peak aortic velocity

  Baseline and 1, 6, 12, and 24 months

• Echocardiographic measurement - Peak transaortic gradient

  Baseline and 1, 6, 12, and 24 months

Study Arms (2)

Angiotensin Receptor Blocker (ARB) Group

EXPERIMENTAL

Participants in this group receive an angiotensin receptor blocker (candesartan, losartan, or valsartan) in addition to standard care after TAVR. As a principle, the ARB is up-titrated toward the target daily dose, but it may be initiated at a lower starting dose based on clinical need. Assigned treatment is continued for up to 24 months. ACE inhibitors, direct renin inhibitors, and angiotensin receptor/neprilysin inhibitors are prohibited.

Drug: Angiotensin Receptor Blocker (ARB)

Control (No ARB) Group

NO INTERVENTION

Participants in this group receive standard care after TAVR without any angiotensin receptor blocker during the study period. ACE inhibitors, direct renin inhibitors, and angiotensin receptor/neprilysin inhibitors are also prohibited in this group. Participants are followed for up to 24 months.

Interventions

Angiotensin Receptor Blocker (ARB) DRUG

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.

Angiotensin Receptor Blocker (ARB) Group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Samjin Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, Seoul, 03080, South Korea

Location

Related Publications (17)

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MeSH Terms

Conditions

Hypertrophy, Left Ventricular; Aortic Valve Stenosis

Interventions

Angiotensin Receptor Antagonists

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Jung-Kyu Han, MD, PhD

CONTACT

+82-2-2072-4870; hpcrates@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Eligible patients are randomized in a 1:1 ratio to one of two parallel groups: an experimental group receiving an angiotensin receptor blocker (ARB) and a control group receiving no ARB. Randomization is stratified by participating site and sex and is managed through an independent web-based interactive web response service (IWRS). This is an open-label study, so treatment assignment is not blinded; however, protocol-defined clinical endpoints are adjudicated by an independent, blinded Clinical Event Adjudication Committee. The assigned treatment is continued for up to 24 months of follow-up, with visits at 1, 6, 12, and 24 months.

Study Record Dates

• First Submitted: June 10, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): June 15, 2030
• Study Completion (Estimated): June 15, 2030
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)