Clinical trial NCT05212597: Open Label RCT for Chronic Severe AR : Entresto vs. CCB/ARB
Official title: Multicenter, Randomized, Open-label Trial to Assess the Efficacy of Sacubitril/Valsartan vs. Amlodipine/Losartan on Left Ventricular Remodeling in Patients With Chronic Severe Aortic Regurgitation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Aortic Valve Insufficiency
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2022-01-28
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy of sacubitril-valsartan compared to the combination of ARB/CCB on left ventricular remodeling in patients with chronic aortic valve regurgitation.

Detailed description: After being informed consent about the study and potential risk, all patients giving written informed consent will undergo a 1 month screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in an open-label manner in a 1:1 ratio to sacubitril-valsartan or amlodipine/losartan.

Eligibility criteria: Inclusion Criteria:

1. Participant over 20 years of age who has not been hospitalized for heart failure
2. Participant with hypertension or systolic blood pressure 125 mmHg or higher
3. NYHA I
4. Participant with chronic severe aortic regurgitation (VCW \>0.6cm)
5. Participant with AV regurgitant volume ≥ 60mL or effective regurgitant orifice area ≥ 0.3 cm2
6. Participant with left ventricular ejection fraction ≥ 55%

Exclusion Criteria:

1. A history of hypersensitivity or allergy to clinical trial drugs or similar compounds or ARB/NEP inhibitors
2. History of angioedema
3. Patients with an ascending aorta dilated by more than 55 mm
4. Patients with aortic valve insufficiency due to hereditary aortic disease (Marfan syndrome, Ehlers-Danlos syndrome)
5. Patients with moderate to severe aortic stenosis
6. Patients with claustrophobia or with metallic implants unsuitable for magnetic resonance imaging
7. History of acute heart failure within 6 weeks and dyspnea of NYHA II or higher
8. Symptomatic hypotension or SBP \< 100 mmHg at screening
9. Patients with renal failure (Estimated GFR \< 30 mL/min/1.73 m2) or on dialysis
10. Significant increase in blood potassium level (Potassium \> 5 mmol/L)
11. Blood AST or ALT value is more than twice the upper limit of normal or symptoms and signs of cirrhosis (history of hepatic coma, history of esophageal varices, history of symptomatic ascites)
12. In case of acute coronary syndrome, stroke, thoracic surgery, and percutaneous coronary angioplasty within 3 months
13. If aortic valve surgery is scheduled within the next 6 months
14. In case of severe mitral valve disease
15. Patients with primary hyperaldosteronism
16. If a woman of childbearing potential has not used double contraception
17. Women who are currently pregnant or lactating
18. When it is judged that there are clinically significant abnormalities in physical examination, diagnostic examination, electrocardiogram, etc. at the time of the screening visit

Primary outcomes:
measure: Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up
timeFrame: Baseline and month 12
Secondary outcomes:
measure: Change of regurgitant volume of aortic valve regurgitation from baseline to 12 months follow-up.
timeFrame: Baseline and month 12
measure: Change of EROA of aortic valve regurgitation from baseline to 12 months follow-up.
timeFrame: Baseline and month 12
measure: Change of LV end-systolic volume from baseline to 12 months follow-up.
timeFrame: Baseline and month 12
measure: Holodiastolic flow reversal in the proximal abdominal aorta and descending thoracic aorta from baseline to 12 months follow-up
timeFrame: Baseline and month 12
measure: Change of NT-proBNP level from baseline to 12 months follow-up.
timeFrame: Baseline and month 12
measure: Aortic valve replacement or repair operation
timeFrame: During 12 months after enrollment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Heart Vascular Stroke Institute, Samsung Medical Center
name: Eun Kyoung Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: