Dapagliflozin Effect on Rheumatic Mitral Stenosis

Heart Failure Clinical Trial

— Dapa-Rhemis  

Official title:

Dapagliflozin Effect on Rheumatic Mitral Stenosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05618223
• Other study ID #: Dapa-Rhemis
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: December 1, 2022
• Est. completion date: June 30, 2023

Study information

• Verified date: November 2022
• Source: Universitas Sebelas Maret
• Contact: An Aldia Asrial, MD
• Phone: +6281229663174
• Email: aaldiaa8[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study is an open-label study on Rheumatic Mitral Stenosis patients, carried out at Sebelas Maret University Hospital Sukoharjo, Panti Rahayu Hospital Purwodadi, and Permata Bunda Hospital Purwodadi. Researchers divided 36 Rheumatic Mitral Stenosis patients sequentially into two groups, the first was the dapagliflozin group which would receive dapagliflozin 10 mg once a day and standard treatment. And the second group will only get standard treatment. Each patient will be examined on PICP, MMP-1, MMP-1/TIMP-1 ratio, TGF-β, Net atrioventricular compliance index, NT-pro BNP, and Kansas City Cardiomyopathy Questionnaire on day 1 and one month after the intervention.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: June 30, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Related Conditions & MeSH terms

• Constriction, Pathologic
• Heart Diseases
• Heart Failure
• Mitral Stenosis
• Mitral Valve Stenosis
• Rheumatic Diseases
• Rheumatic Heart Disease

Intervention

Drug:
• Dapagliflozin
Dapagliflozin 10 mg once daily in addition to standard therapy

Locations

Country	Name	City	State
Indonesia	Sebelas Maret University Hospital	Sukoharjo	Central Java

Sponsors (1)

Lead Sponsor	Collaborator
Universitas Sebelas Maret

Country where clinical trial is conducted

Indonesia, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvements of Biomolecular Parameters	PICP in pg/ml, MMP-1 in pg/ml, MMP-1/TIMP-1 ratio, TGF-ß in pg/ml, NT-ProBNP in pg/ml	4 weeks
Primary	Improvements of Clinical Parameters	Kansas City Cardiomyopathy Questionnaire (KCCQ) scores are scaled 0-100 (the higher score indicates a better condition)	4 weeks
Primary	Improvements of Echocardiography Parameters	Net atrioventricular compliance in mL/mmHG, mitral valve gradient in mmHg and mPAP in mmHg	4 weeks
Secondary	Major Adverse Cardiac Events	All cause cardiac rehospitalization	4 weeks