Open Label RCT for Chronic Severe AR : Entresto vs. CCB/ARB

Phase 2

Recruiting

• Conditions: Aortic Valve Insufficiency
• Interventions: Drug: Sacubitril-valsartan; Drug: Amlodipine-losartan

• Registration Number: NCT05212597
• Lead Sponsor: Samsung Medical Center

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.

Study Timeline

• Status Verified: 2022-01
• Study Start: 2022-01-12
• Study First Submitted: 2022-01-27
• Study First Submitted QC: 2022-01-27
• Last Update Submitted: 2022-01-27
• Study First Posted: 2022-01-28
• Last Update Posted: 2022-01-28
• Primary Completion: 2023-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sacubitril-Valsartan Group	Sacubitril-valsartan	Participant start Sacubitril/Valsartan tablet 50mg twice a day and uptitrate to 100mg twice a day. Participants take the maximum dose considering blood pressure for a total of 48 weeks.
Amlodipine-Losartan group	Amlodipine-losartan	Participant start amlodipine/losartan 25/2.5mg once a day and uptitrate to 5/100mg once a day. Participants take the maximum dose considering blood pressure for a total of 48 weeks.

Primary Outcome Measures

Name	Time	Method
Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up	Baseline and month 12	Change = \[LVEDV on CMR at 12 months\]-\[LVEDV on CMR at baseline\]

Secondary Outcome Measures

Name	Time	Method
Change of LV end-systolic volume from baseline to 12 months follow-up.	Baseline and month 12	Change = \[LVEDV at 12 months\]-\[LVEDV at baseline\]
Aortic valve replacement or repair operation	During 12 months after enrollment	Any surgical event for correction of AR
Change of EROA of aortic valve regurgitation from baseline to 12 months follow-up.	Baseline and month 12	Measurement of regurgitant volume of AR is derived from Doppler imaging on echocardiography.; Change = \[regurgitant volume at 12 months\]-\[regurgitant volume at baseline\]
Holodiastolic flow reversal in the proximal abdominal aorta and descending thoracic aorta from baseline to 12 months follow-up	Baseline and month 12	presence or absence of holodiastolic flow reversal in the proximal abdominal and descending thoracic aorta on echocardiography
Change of regurgitant volume of aortic valve regurgitation from baseline to 12 months follow-up.	Baseline and month 12	Change = \[regurgitant volume at 12 months\]-\[regurgitant volume at baseline\]
Change of NT-proBNP level from baseline to 12 months follow-up.	Baseline and month 12	Change =\[NT-proBNP at 12 months\]-\[NTproBNP at baseline\]

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of