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

Primary Purpose

Aortic Valve Insufficiency

Status

Recruiting

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Sacubitril-valsartan

Amlodipine-losartan

About this trial

This is an interventional treatment trial for Aortic Valve Insufficiency

Eligibility Criteria

20 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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%

Exclusion Criteria:

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
If a woman of childbearing potential has not used double contraception
Women who are currently pregnant or lactating
When it is judged that there are clinically significant abnormalities in physical examination, diagnostic examination, electrocardiogram, etc. at the time of the screening visit

Sites / Locations

Samsung Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sacubitril-Valsartan Group

Amlodipine-Losartan group

Arm 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.

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.

Outcomes

Primary Outcome Measures

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]

Secondary Outcome Measures

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]

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]

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

Change = [LVEDV at 12 months]-[LVEDV at baseline]

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

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

Change =[NT-proBNP at 12 months]-[NTproBNP at baseline]

Aortic valve replacement or repair operation

Any surgical event for correction of AR

Full Information

NCT ID

NCT05212597

First Posted

January 27, 2022

Last Updated

January 27, 2022

Sponsor

Samsung Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT05212597

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 12, 2022 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Samsung Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aortic Valve Insufficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sacubitril-Valsartan Group

Arm Type

Active Comparator

Arm 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.

Arm Title

Amlodipine-Losartan group

Arm Type

Placebo Comparator

Arm 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.

Intervention Type

Drug

Intervention Name(s)

Sacubitril-valsartan

Other Intervention Name(s)

Entresto

Intervention Description

50mg~100mg twice daily

Intervention Type

Drug

Intervention Name(s)

Amlodipine-losartan

Other Intervention Name(s)

Amosartan

Intervention Description

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

Primary Outcome Measure Information:

Title

Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up

Description

Change = [LVEDV on CMR at 12 months]-[LVEDV on CMR at baseline]

Time Frame

Baseline and month 12

Secondary Outcome Measure Information:

Title

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

Description

Change = [regurgitant volume at 12 months]-[regurgitant volume at baseline]

Time Frame

Baseline and month 12

Title

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

Description

Measurement of regurgitant volume of AR is derived from Doppler imaging on echocardiography. Change = [regurgitant volume at 12 months]-[regurgitant volume at baseline]

Time Frame

Baseline and month 12

Title

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

Description

Change = [LVEDV at 12 months]-[LVEDV at baseline]

Time Frame

Baseline and month 12

Title

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

Description

presence or absence of holodiastolic flow reversal in the proximal abdominal and descending thoracic aorta on echocardiography

Time Frame

Baseline and month 12

Title

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

Description

Change =[NT-proBNP at 12 months]-[NTproBNP at baseline]

Time Frame

Baseline and month 12

Title

Aortic valve replacement or repair operation

Description

Any surgical event for correction of AR

Time Frame

During 12 months after enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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% Exclusion Criteria: 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 If a woman of childbearing potential has not used double contraception Women who are currently pregnant or lactating When it is judged that there are clinically significant abnormalities in physical examination, diagnostic examination, electrocardiogram, etc. at the time of the screening visit

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Eun Kyoung Kim, MD. PhD

Phone

82-2-3410-3419

ekbobi.kim@samsung.com

First Name & Middle Initial & Last Name or Official Title & Degree

Sung Ji Park, MD, PhD

Phone

82-2-3410-3419

sungji.park@samsung.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eun Kyoung Kim, MD, PhD

Organizational Affiliation

Heart Vascular Stroke Institute, Samsung Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eun Kyoung Kim, MD PhD

Phone

82234103419

ekbobi.kim@samsung.com

First Name & Middle Initial & Last Name & Degree

Ji Hoon Kim, MD

Phone

82234103419

jh9933.kim@samsung.com

12. IPD Sharing Statement

Learn more about this trial

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

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