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Tricuspid RegurgitationPhase 3PROVENCT04345796

Pharmacological Reduction of Right Ventricular Enlargement

A Phase 3 study testing Carvedilol+Empagliflozin, Carvedilol and Empagliflozin in people with Tricuspid Regurgitation and Right Ventricular Dilatation, run by Asan Medical Center at 3 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Functional tricuspid regurgitation (TR) has been regarded as a secondary phenomenon of heart failure (HF), mitral valve (MV) disease or atrial fibrillation. Regardless of left ventricular (LV) function or pulmonary artery pressure, presence of moderate or greater functional TR is associated with poor prognosis. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Carvedilol+Empagliflozin, Carvedilol and Empagliflozin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
56 participants
Where
3 sitesSouth Korea
Study dates
15 Feb 2021to 3 Jun 2024
Phase
Phase 3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must agree to the study protocol and provide written informed consent
  • Outpatients ≥ 20 years of age, male or female
  • Patients with severe functional tricuspid regurgitation
  • TR whose vena contracta ≥0.7cm or central jet area > 10 square cm and which lasted > 6 months under medical treatment
  • LV ejection fraction ≥ 50%
  • Dyspnea of NYHA functional class II or III

Who cannot join

  • History of hypersensitivity or allergy to the study drugs, drugs of similar chemical classes, as well as known or suspected contraindications to the study drug
  • Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor
  • Significant left-sided valve disease
  • Left ventricular ejection fraction <40%
  • Marked bradycardia (<50 beats/min) or 2nd or 3rd degree AVB, sinus node dysfunction
  • Severe pulmonary hypertension: TR Vmax >4m/s at screening (including Cor pulmonale)
Show all 23Show fewer
  • Medical history of hospitalization within 6 weeks
  • Current acute decompensated heart failure or dyspnea of NYHA functional class IV
  • Symptomatic hypotension and/or a SBP < 90 mmHg at screening Estimated GFR < 30 mL/min/1.73 square m
  • History of ketoacidosis, Type 1 diabetes
  • Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 2 x upper limit of normal (ULN) at screening visit (Visit 0), history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt.
  • Acute coronary syndrome, stroke, severe peripheral artery disease or major CV surgery or PCI within 3 months
  • History of severe pulmonary disease (asthma, COPD with bronchial hypersensitivity)
  • Secondary hypertension such as pheochromocyotoma
  • Acute pulmonary thromboembolism
  • Variant angina, vocal cord edema, severe allergic rhinitis
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a barrier method plus a hormonal method
  • Pregnant or nursing (lactating) women
  • Contraindication for MRI
  • Presence of pacemaker or ICD, implanted metallic objects, claustrophobia
  • Severe beat-to-beat variation
  • Galactose intolerance, Lapp lactose deficiency, glucose-galactose malabsorption
  • Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study

Trial locations and contacts

3 sites in 1 country.

South Korea3 sites

  • Asan Medical Center

    Seoul, 138-736

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

Other trials in South Korea

About this study

Official title: Multicenter, Randomized, 2 x 2 Factorial, Phase 3 Study to Assess the Efficacy of Carvedilol and Empagliflozin on Improvement of Right Ventricular Remodeling in Patients With Severe Functional Tricuspid Regurgitation

Functional tricuspid regurgitation (TR) has been regarded as a secondary phenomenon of heart failure (HF), mitral valve (MV) disease or atrial fibrillation. Regardless of left ventricular (LV) function or pulmonary artery pressure, presence of moderate or greater functional TR is associated with poor prognosis. When a patient develops functional TR, it causes RV dilation and tricuspid annular enlargement, which also lead to deterioration of TR. A vicious cycle of significant TR, RV volume overload, tricuspid annular dilation and consequent aggravation of TR is accepted as a main determinant of the poor clinical outcome of patients with TR. Therefore, therapies that induce reverse remodeling of the RV and consequently reduce TR, may improve clinical outcomes. However, there have been no proven medical therapies for TR. The investigators hypothesize that carvedilol or empagliflozin is effective on improving RV remodeling in patients with functional severe TR and try to examine this hypothesis in a multicenter, 2x2 factorial, and randomized comparison study using cardiac MRI.

Read the detailed description

Functional tricuspid regurgitation (TR) has been regarded as a secondary phenomenon of heart failure (HF), mitral valve (MV) disease or atrial fibrillation. The prevalence of functional TR was reported to be 25-64% in patients with either ischemic or non-ischemic cardiomyopathy. Regardless of left ventricular (LV) function or pulmonary artery pressure, presence of moderate or greater functional TR is associated with poor prognosis. When a patient develops functional TR, it causes RV dilation and tricuspid annular enlargement, which also lead to deterioration of TR. A vicious cycle of significant TR, RV volume overload, tricuspid annular dilation and consequent aggravation of TR is accepted as a main determinant of the poor clinical outcome of patients with TR. Because the quantitative assessment of RV size and function using echocardiography is often limited due to the complex geometry of RV, cardiac magnetic resonance imaging (MRI) has emerged as a gold standard for evaluating RV volume and function with excellent accuracy and reproducibility. The investigators previously reported that RV end-systolic volume index (ESVI) and RV end-diastolic volume index (EDVI) measured by MRI were significantly larger in severe TR patients, and also found that preoperative RV ESVI and RV ejection fraction (EF) on MRI were independent predictors of cardiac death and postoperative adverse events in patients who underwent TV surgery for severe functional TR. Therefore, therapies that induce reverse remodeling of the RV and consequently reduce TR, may improve clinical outcomes. However, there have been no proven medical therapies for TR. The morbidity and mortality of patients with functional TR remain high and novel therapeutic agents are needed to improve the prognosis of patients with functional TR. The investigators hypothesize that carvedilol or empagliflozin is effective on improving RV remodeling in patients with functional severe TR and try to examine this hypothesis in a multicenter, 2x2 factorial, and randomized comparison study using cardiac MRI.

Being tested
Carvedilol+Empagliflozin, Carvedilol, Empagliflozin, Placebo
Medical subject headings
Tricuspid Valve Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carvedilol+EmpagliflozinDrug

    Also called Dilatrend SR+Jardiance

    Group A

  • CarvedilolDrug

    Also called Dilatrend SR

    Group B

  • EmpagliflozinDrug

    Also called Jardiance

    Group C

  • PlaceboDrug

    Also called Matching placebo of Dilatrend SR

    Group D

Study groups in NCT04345796
Study groupRoleWhat they receive
carvedilol+empagliflozinActive comparatorPatients will receive carvedilol SR 16mg and empagliflozin 10mg qd.
Receives: Drug: Carvedilol+Empagliflozin
carvedilol aloneActive comparatorPatients will receive carvedilol SR 16mg alone.
Receives: Drug: Carvedilol
empagliflozin aloneActive comparatorPatients will receive empagliflozin 10mg and matching placebo of carvedilol.
Receives: Drug: Empagliflozin
placeboPlacebo comparatorPatients will receive matching placebo of carvedilol.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of RV end-systolic volume index

    Change of RV end-systolic volume index by cardiac MRI

    Measured: from baseline to 12 months follow-up

Secondary outcomes (5)

  1. Change of RV end-diastolic volume index

    Change of RV end-diastolic volume index by cardiac MRI

    Measured: from baseline to 12 months follow-up

  2. Change of RV ejection fraction

    Change of RV ejection fraction by cardiac MRI

    Measured: from baseline to 12 months follow-up

  3. Change of vena contract width of TR

    Change of vena contract width of TR by echocardiography

    Measured: from baseline to 12 months follow-up

  4. Occurrences of death from cardiovascular causes or hospitalization for heart failure

    Clinical outcome

    Measured: the entire follow-up period (continuing until 12 months after the last patient was enrolled)

  5. Occurrences of death from any causes

    Clinical outcome

    Measured: the entire follow-up period (continuing until 12 months after the last patient was enrolled)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2020
  2. Study start15 Feb 2021
  3. Primary completion3 Jun 2024
  4. Study completion3 Jun 2024

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
2 x 2 factorial
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04345796
Sponsor's protocol ID
2020-0127
Acronym
PROVE
Status last verified
Apr 2025
First submitted
12 Apr 2020
Last updated
6 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kim GY, Lim SM, Yang DH, Lee JE, Lee S, Park SJ, Hwang IC, Yoon YE, Shim CY, Kim HK, Yun SC, Song JM, Kang DH. Effect of empagliflozin with or without carvedilol on tricuspid regurgitation and right ventricular remodeling: PROVE trial. J Cardiovasc Imaging. 2026 Sep 14;34(1):32. doi: 10.1186/s44348-026-00095-4.

    PubMed 42736580

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Carvedilol+Empagliflozin, Carvedilol and Empagliflozin in people with Tricuspid Regurgitation and Right Ventricular Dilatation, run by Asan Medical Center at 3 sites 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 23 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: finished, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of RV end-systolic volume index (time frame: from baseline to 12 months follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04345796, which also lists 1 linked publication.

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 6 Apr 2025.

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