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

Aortic Valve Insufficiency Clinical Trial

— REVERSE-AR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05212597
• Other study ID #: reverseAR
• Status: Recruiting
• Phase: Phase 2
• Start date: January 12, 2022
• Est. completion date: December 2024

Study information

• Verified date: January 2022
• Source: Samsung Medical Center
• Contact: Eun Kyoung Kim, MD. PhD
• Phone: 82-2-3410-3419
• Email: ekbobi.kim[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Insufficiency

Intervention

Drug:
• Sacubitril-valsartan
50mg~100mg twice daily
• Amlodipine-losartan
amlodipine/losartan 2.5/25mg ~ 5/100mg once daily

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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