SGLT2 Inhibitor for Severe Tricuspid Regurgitation (Reduction-TR)

Multicenter, Randomized, Controlled Trial to Assess the Efficacy of Sodium Glucose Cotransporter-2 Inhibitor add-on Treatment in Patients With Severe Tricuspid Regurgitation

The purpose of this study to identify the efficacy of sodium glucose cotransporter 2 inhibitors add-on treatment on right ventricular remodeling and the amount of severe tricuspid regurgitation (TR) in patients with isolated severe TR.

Study Overview

• Status: Recruiting
• Conditions: Tricuspid Regurgitation
• Intervention / Treatment: Drug: Dapagliflozin Propanediol Hydrate 12.3 mg

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 SGLT2i add-on group or conventional treatment group.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eun Kyoung Kim, MD. PhD; Phone Number: 82-2-3410-3419; Email: ekbobi.kim@samsung.com
• Study Contact Backup: Name: Ji Hoon Kim, MD, PhD; Phone Number: 82-2-3410-3419; Email: jh9933.kim@samsung.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Eun Kyoung Kim, MD PhD; Phone Number: 82234103419; Email: ekbobi.kim@samsung.com
    • Contact: Ji Hoon Kim, MD; Phone Number: 82234103419; Email: jh9933.kim@samsung.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant over 20 years of age who understands the research protocol and has written informed consent

2. Participant with severe tricuspid valve regurgitation

   • Vena contracta width > 0.7cm or effective regurgitant orifice (ERO)≥40mm2 for more than 1 month despite medical treatment
   • Participant with left ventricular ejection fraction ≥ 40%
   • Participant with NYHA class II or more

Exclusion Criteria:

1. Patient with severe mitral valve or aortic valve disease
2. Left ventricular ejection fraction less than 40%*
3. Patient with severe pulmonary hypertension (TR Vmax > 4m/s)
4. Patient with acute heart failure or dyspnea of NYHA functional class IV or higher
5. Symptomatic hypotension or systolic blood pressure < 90 mmHg at screening
6. Patient with severe lung disease (asthma, obstructive pulmonary disease, acute pulmonary embolism)
7. Patients with renal failure (Estimated GFR < 30 mL/min/1.73 m2) or on dialysis
8. Patient with Type 1 diabetes
9. If a woman of childbearing potential has not used double contraception
10. Patients with claustrophobia or with metallic implants unsuitable for magnetic resonance imaging
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. Life expectancy is less than one year
13. Patient who already take SGLT-2 inhibitor
14. A history of hypersensitivity or allergy to SGLT2 inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SGLT2 inhibitor group; Participants will take dapagliflozin propanediol hydrate 12.3 mg once a day for a total of 48 weeks.	Drug: Dapagliflozin Propanediol Hydrate 12.3 mg; Forxiga 10mg will be added on the conventional treatment for SGL2 inhibitor group.; Other Names: Forxiga Tablet 10mg
No Intervention: Conventional treatment group; Participants will continue the existing medications for severe TR.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of RVESVi by CMR from baseline to 12 months follow-up (∆RVESVi)	RVESV index at 12 months - RVESV index at baseline	Baseline and month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of RVEDVi by CMR from baseline to 12 months follow-up (∆RVEDVi)	RVEDV index at 12 months - RVEDV index at baseline	Baseline and month 12
Difference of RV ejection fraction by CMR from baseline to 12 months follow-up (∆RVEF)	RVEF at 12 months - RVEF at baseline	Baseline and month 12
Difference of Vena contracta width of TR by echocardiography from baseline to 12 months follow-up (∆VCW)	TR VCW at 12 months - TR VCW at baseline	Baseline and month 12
Difference of TV annulus diameter by echocardiography from baseline to 12 months follow-up	Tricuspid annulus diameter at 12 months - Tricuspid annulus diameter at baseline	Baseline and month 12
Difference of TR volume by CMR from baseline to 12 months follow-up	TR volume at 12 months - TR volume at baseline	Baseline and month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of cardiovascular death or hospitalization for right heart failure* during 12 months	development of cardiovascular death or admission for heart failure	12 months after enrollment
Occurrence of tricuspid valve surgery during 12 months	TV surgery	12 months after enrollment
Difference of NT-proBNP from baseline to 12 months follow-up	NT-proBNP at 12 months - NT-proBNP at baseline	Baseline and month 12
Occurrence of renal dysfunction (creatinine > 2mg/dL)	Newly developed renal dysfunction during follow-up period	12 months after enrollment

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Sung Ji Park, MD, PhD, Heart Vascular Stroke Institute, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Anticipated): April 13, 2024
• Study Completion (Anticipated): March 3, 2025

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Estimate): January 16, 2023

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: SGLT2 inhibitor; tricuspid regurgitation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Tricuspid Valve Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: Reduction TR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No