Open Label RCT for Chronic Severe AR : Entresto vs. CCB/ARB (REVERSE-AR)

Samsung Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Aortic Valve Insufficiency

Treatments: Drug: Sacubitril-valsartan; Drug: Amlodipine-losartan

Study type: Interventional

Funder types: Other

Identifiers

NCT05212597

reverseAR

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 20 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

100 participants in 2 patient groups, including a placebo group

Sacubitril-Valsartan Group

Active Comparator group

Description:

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.

Treatment:

Drug: Sacubitril-valsartan

Amlodipine-Losartan group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Amlodipine-losartan