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

NCT05212597 | Unknown Phase 2 DMC

• 1 other identifier: reverseAR
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Aortic Valve Insufficiency

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change of regurgitant volume of aortic valve regurgitation from baseline to 12 months follow-up.

  Baseline and month 12

• Change of EROA of aortic valve regurgitation from baseline to 12 months follow-up.

  Baseline and month 12

• Change of LV end-systolic volume from baseline to 12 months follow-up.

  Baseline and month 12

• Holodiastolic flow reversal in the proximal abdominal aorta and descending thoracic aorta from baseline to 12 months follow-up

  Baseline and month 12

• Change of NT-proBNP level from baseline to 12 months follow-up.

  Baseline and month 12

Study Arms (2)

Sacubitril-Valsartan Group

ACTIVE COMPARATOR

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.

Drug: Sacubitril-valsartan

Amlodipine-Losartan group

PLACEBO COMPARATOR

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.

Drug: Amlodipine-losartan

Interventions

Sacubitril-valsartan DRUG

50mg\~100mg twice daily

Also known as: Entresto

Sacubitril-Valsartan Group

Amlodipine-losartan DRUG

amlodipine/losartan 2.5/25mg \~ 5/100mg once daily

Also known as: Amosartan

Amlodipine-Losartan group

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• A history of hypersensitivity or allergy to clinical trial drugs or similar compounds or ARB/NEP inhibitors
• History of angioedema
• Patients with an ascending aorta dilated by more than 55 mm
• Patients with aortic valve insufficiency due to hereditary aortic disease (Marfan syndrome, Ehlers-Danlos syndrome)
• Patients with moderate to severe aortic stenosis
• Patients with claustrophobia or with metallic implants unsuitable for magnetic resonance imaging
• History of acute heart failure within 6 weeks and dyspnea of NYHA II or higher
• Symptomatic hypotension or SBP \< 100 mmHg at screening
• Patients with renal failure (Estimated GFR \< 30 mL/min/1.73 m2) or on dialysis
• Significant increase in blood potassium level (Potassium \> 5 mmol/L)
• 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)
• In case of acute coronary syndrome, stroke, thoracic surgery, and percutaneous coronary angioplasty within 3 months
• If aortic valve surgery is scheduled within the next 6 months
• In case of severe mitral valve disease
• Patients with primary hyperaldosteronism

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Aortic Valve Insufficiency

Interventions

sacubitril and valsartan sodium hydrate drug combination; amlodipine-losartan drug combination

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Eun Kyoung Kim, MD, PhD

  Heart Vascular Stroke Institute, Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eun Kyoung Kim, MD. PhD

CONTACT

82-2-3410-3419; ekbobi.kim@samsung.com

Sung Ji Park, MD, PhD

CONTACT

82-2-3410-3419; sungji.park@samsung.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: January 28, 2022
• Study Start: January 12, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: January 28, 2022

Record last verified: 2022-01

Locations

KR (1)