Dapagliflozin Effect on Rheumatic Mitral Stenosis

NCT05618223 | Unknown Phase 3

• 1 other identifier: Dapa-Rhemis
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatic mitral stenosis remains a health problem in developing countries. Progressive fibrosis of the valves and myocardium is the main pathophysiology that plays an important role. Dapagliflozin has various beneficial effects on the heart by reducing fibrosis, reducing inflammation, and improving patient quality of life. However, the role of this therapy is unknown in patients with rheumatic mitral stenosis.

Conditions

Rheumatic Heart Disease; Heart Failure; Mitral Stenosis

Keywords

rheumatic heart disease; mitral stenosis; heart failure

Outcome Measures

Primary Outcomes (3)

• Improvements of Biomolecular Parameters

  PICP in pg/ml, MMP-1 in pg/ml, MMP-1/TIMP-1 ratio, TGF-β in pg/ml, NT-ProBNP in pg/ml

  4 weeks

• Improvements of Clinical Parameters

  Kansas City Cardiomyopathy Questionnaire (KCCQ) scores are scaled 0-100 (the higher score indicates a better condition)

  4 weeks

• Improvements of Echocardiography Parameters

  Net atrioventricular compliance in mL/mmHG, mitral valve gradient in mmHg and mPAP in mmHg

  4 weeks

Secondary Outcomes (1)

• Major Adverse Cardiac Events

  4 weeks

Study Arms (2)

Dapagliflozin group

EXPERIMENTAL

Dapagliflozin 10 mg once a day and standard treatment

Drug: Dapagliflozin

Control group

NO INTERVENTION

Standard treatment only.

Interventions

Dapagliflozin DRUG

Dapagliflozin 10 mg once daily in addition to standard therapy

Dapagliflozin group

Eligibility Criteria

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

You may qualify if:

• Severe mitral stenosis by echocardiographic examination of the planimetric method with morphology that supports the etiology of rheumatic
• Heart failure in functional class II-III
• Dapagliflozin naive
• Exception Criteria:
• Other significant valve diseases
• Pregnant or breastfeeding
• Unstable hemodynamic conditions including cardiogenic shock
• history of mitral valve replacement/repair or mitral balloon valvuloplasty
• history of hypoglycemia
• eGFR below 25 mmHg
• diffuse pulmonary fibrosis

Sponsors & Collaborators

• Universitas Sebelas Maret: lead

Study Sites (1)

Sebelas Maret University Hospital

Sukoharjo, Central Java, 58192, Indonesia

Location

Related Publications (6)

• Banerjee T, Mukherjee S, Ghosh S, Biswas M, Dutta S, Pattari S, Chatterjee S, Bandyopadhyay A. Clinical significance of markers of collagen metabolism in rheumatic mitral valve disease. PLoS One. 2014 Mar 6;9(3):e90527. doi: 10.1371/journal.pone.0090527. eCollection 2014.

  PMID: 24603967 BACKGROUND

• Banerjee T, Mukherjee S, Biswas M, Dutta S, Chatterjee S, Ghosh S, Pattari S, Nanda NC, Bandyopadhyay A. Circulating carboxy-terminal propeptide of type I procollagen is increased in rheumatic heart disease. Int J Cardiol. 2012 Apr 5;156(1):117-9. doi: 10.1016/j.ijcard.2012.01.026. Epub 2012 Feb 1. No abstract available.

  PMID: 22305814 BACKGROUND

• Lin YW, Chen CY, Shih JY, Cheng BC, Chang CP, Lin MT, Ho CH, Chen ZC, Fisch S, Chang WT. Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation-Induced Myocardial Dysfunction. J Am Heart Assoc. 2021 Apr 6;10(7):e019274. doi: 10.1161/JAHA.120.019274. Epub 2021 Mar 20.

  PMID: 33749310 BACKGROUND

• Nassif ME, Windsor SL, Tang F, Khariton Y, Husain M, Inzucchi SE, McGuire DK, Pitt B, Scirica BM, Austin B, Drazner MH, Fong MW, Givertz MM, Gordon RA, Jermyn R, Katz SD, Lamba S, Lanfear DE, LaRue SJ, Lindenfeld J, Malone M, Margulies K, Mentz RJ, Mutharasan RK, Pursley M, Umpierrez G, Kosiborod M. Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial. Circulation. 2019 Oct 29;140(18):1463-1476. doi: 10.1161/CIRCULATIONAHA.119.042929. Epub 2019 Sep 16.

  PMID: 31524498 BACKGROUND

• Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor. Cardiovasc Drugs Ther. 2017 Apr;31(2):119-132. doi: 10.1007/s10557-017-6725-2.

  PMID: 28447181 BACKGROUND

• Li G, Zhao C, Fang S. SGLT2 promotes cardiac fibrosis following myocardial infarction and is regulated by miR-141. Exp Ther Med. 2021 Jul;22(1):715. doi: 10.3892/etm.2021.10147. Epub 2021 May 3.

  PMID: 34007324 BACKGROUND

MeSH Terms

Conditions

Rheumatic Heart Disease; Heart Failure; Mitral Valve Stenosis

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Rheumatic Fever; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases

Study Officials

• An Aldia Asrial, MD

  Universitas Sebelas Maret

  PRINCIPAL INVESTIGATOR

Central Study Contacts

An Aldia Asrial, MD

CONTACT

+6281229663174; aaldiaa8@gmail.com

Anggit Pudjiastuti, MD

CONTACT

+6285225036705; anggituy@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: An Aldia Asrial, MD, FIHA (Principal investigator)

Model Details: Pre and post-test design

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 16, 2022
• Study Start: December 1, 2022
• Primary Completion: May 31, 2023
• Study Completion: June 30, 2023
• Last Updated: November 21, 2022

Record last verified: 2022-11

Locations

ID (1)