Clinical trial NCT05618223: Dapagliflozin Effect on Rheumatic Mitral Stenosis
Official title: Dapagliflozin Effect on Rheumatic Mitral Stenosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rheumatic Heart Disease
Heart Failure
Mitral Stenosis
Keywords: rheumatic heart disease
mitral stenosis
heart failure
Lead sponsor: Universitas Sebelas Maret
Sponsor class: OTHER
First posted: 2022-11-16
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pre and post-test design
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Improvements of Biomolecular Parameters
timeFrame: 4 weeks
measure: Improvements of Clinical Parameters
timeFrame: 4 weeks
measure: Improvements of Echocardiography Parameters
timeFrame: 4 weeks
Secondary outcomes:
measure: Major Adverse Cardiac Events
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Sukoharjo
country: Indonesia
facility: Sebelas Maret University Hospital
state: Central Java
Study officials:
affiliation: Universitas Sebelas Maret
name: An Aldia Asrial, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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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.
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.
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.