Aortic Valve InsufficiencyPhase 2REVERSE-ARNCT05212597
Open Label RCT for Chronic Severe AR : Entresto vs. CCB/ARB
A Phase 2 study testing Sacubitril-valsartan and Amlodipine-losartan in people with Aortic Valve Insufficiency, run by Samsung Medical Center at 1 site in South Korea.
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. Read more about this study
- Who is it for?
- Ages 20 to 90 years
- Conditions the study is for
- Aortic Valve Insufficiency
- What is being tested?
- Sacubitril-valsartan and Amlodipine-losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteSouth Korea
- Study dates
- 12 Jan 2022to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Samsung Medical Center
Seoul, 06351
Eun Kyoung Kim, MD PhD, 82234103419, ekbobi.kim@samsung.com
Ji Hoon Kim, MD, 82234103419, jh9933.kim@samsung.com
About this study
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
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.
Read the 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.
- Conditions
- Aortic Valve Insufficiency
- Being tested
- Sacubitril-valsartan, Amlodipine-losartan
- Medical subject headings
- Aortic Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-valsartanDrug
Also called Entresto
50mg~100mg twice daily
Amlodipine-losartanDrug
Also called Amosartan
amlodipine/losartan 2.5/25mg ~ 5/100mg once daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Amlodipine-losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]
Measured: Baseline and month 12
Secondary outcomes (6)
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]
Measured: Baseline and month 12
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]
Measured: Baseline and month 12
Change of LV end-systolic volume from baseline to 12 months follow-up.
Change = [LVEDV at 12 months]-[LVEDV at baseline]
Measured: Baseline and month 12
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
Measured: Baseline and month 12
Change of NT-proBNP level from baseline to 12 months follow-up.
Change =[NT-proBNP at 12 months]-[NTproBNP at baseline]
Measured: Baseline and month 12
Aortic valve replacement or repair operation
Any surgical event for correction of AR
Measured: During 12 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start12 Jan 2022
- Primary completionDec 2023 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic Valve InsufficiencyStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eun Kyoung Kim, Samsung Medical Center
- Investigators
- Eun Kyoung Kim, MD, PhD, Principal investigator, Heart Vascular Stroke Institute, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05212597
- Sponsor's protocol ID
- reverseAR
- Acronym
- REVERSE-AR
- Status last verified
- Jan 2022
- First submitted
- 27 Jan 2022
- Last updated
- 28 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05212597
- Acronym / sponsor ID
- REVERSE-AR / reverseAR
- Conditions
- Aortic Valve Insufficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 12 Jan 2022 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 28 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril-Valsartan Group | Active comparator | Drug: Sacubitril-valsartanParticipant 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 | Placebo comparator | Drug: Amlodipine-losartanParticipant 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. |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril-valsartanAlso: Entresto50mg~100mg twice daily | Drug | Sacubitril-Valsartan Group |
| Amlodipine-losartanAlso: Amosartanamlodipine/losartan 2.5/25mg ~ 5/100mg once daily | Drug | Amlodipine-Losartan group |
Primary outcome
Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up
Time frame: Baseline and month 12
Change = [LVEDV on CMR at 12 months]-[LVEDV on CMR at baseline]
6 secondary outcomes
Change of regurgitant volume of aortic valve regurgitation from baseline to 12 months follow-up.
Time frame: Baseline and month 12
Change of EROA of aortic valve regurgitation from baseline to 12 months follow-up.
Time frame: Baseline and month 12
Change of LV end-systolic volume from baseline to 12 months follow-up.
Time frame: Baseline and month 12
Holodiastolic flow reversal in the proximal abdominal aorta and descending thoracic aorta from baseline to 12 months follow-up
Time frame: Baseline and month 12
Change of NT-proBNP level from baseline to 12 months follow-up.
Time frame: Baseline and month 12
Aortic valve replacement or repair operation
Time frame: During 12 months after enrollment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eun Kyoung Kim, MD, PhD principal investigator
Heart Vascular Stroke Institute, Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacubitril-valsartan and Amlodipine-losartan in people with Aortic Valve Insufficiency, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eun Kyoung Kim, MD. PhD (82-2-3410-3419, ekbobi.kim@samsung.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up (time frame: Baseline and month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2022.