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Dapagliflozin Effect on Rheumatic Mitral Stenosis (Dapa-Rhemis)

Primary Purpose

Rheumatic Heart Disease, Heart Failure, Mitral Stenosis

Status
Not yet recruiting
Phase
Phase 3
Locations
Indonesia
Study Type
Interventional
Intervention
Dapagliflozin
Sponsored by
Universitas Sebelas Maret
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatic Heart Disease focused on measuring rheumatic heart disease, mitral stenosis, heart failure

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sebelas Maret University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Dapagliflozin group

Control group

Arm Description

Dapagliflozin 10 mg once a day and standard treatment

Standard treatment only.

Outcomes

Primary Outcome Measures

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
Improvements of Clinical Parameters
Kansas City Cardiomyopathy Questionnaire (KCCQ) scores are scaled 0-100 (the higher score indicates a better condition)
Improvements of Echocardiography Parameters
Net atrioventricular compliance in mL/mmHG, mitral valve gradient in mmHg and mPAP in mmHg

Secondary Outcome Measures

Major Adverse Cardiac Events
All cause cardiac rehospitalization

Full Information

First Posted
November 8, 2022
Last Updated
November 16, 2022
Sponsor
Universitas Sebelas Maret
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1. Study Identification

Unique Protocol Identification Number
NCT05618223
Brief Title
Dapagliflozin Effect on Rheumatic Mitral Stenosis
Acronym
Dapa-Rhemis
Official Title
Dapagliflozin Effect on Rheumatic Mitral Stenosis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2022 (Anticipated)
Primary Completion Date
May 31, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universitas Sebelas Maret

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatic Heart Disease, Heart Failure, Mitral Stenosis
Keywords
rheumatic heart disease, mitral stenosis, heart failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Pre and post-test design
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozin group
Arm Type
Experimental
Arm Description
Dapagliflozin 10 mg once a day and standard treatment
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Standard treatment only.
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
Dapagliflozin 10 mg once daily in addition to standard therapy
Primary Outcome Measure Information:
Title
Improvements of Biomolecular Parameters
Description
PICP in pg/ml, MMP-1 in pg/ml, MMP-1/TIMP-1 ratio, TGF-β in pg/ml, NT-ProBNP in pg/ml
Time Frame
4 weeks
Title
Improvements of Clinical Parameters
Description
Kansas City Cardiomyopathy Questionnaire (KCCQ) scores are scaled 0-100 (the higher score indicates a better condition)
Time Frame
4 weeks
Title
Improvements of Echocardiography Parameters
Description
Net atrioventricular compliance in mL/mmHG, mitral valve gradient in mmHg and mPAP in mmHg
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Major Adverse Cardiac Events
Description
All cause cardiac rehospitalization
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
An Aldia Asrial, MD
Phone
+6281229663174
Email
aaldiaa8@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Anggit Pudjiastuti, MD
Phone
+6285225036705
Email
anggituy@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
An Aldia Asrial, MD
Organizational Affiliation
Universitas Sebelas Maret
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sebelas Maret University Hospital
City
Sukoharjo
State/Province
Central Java
ZIP/Postal Code
58192
Country
Indonesia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
An Aldia Asrial, MD
Phone
+6281229663174
Email
aaldiaa8@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24603967
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.
Results Reference
background
PubMed Identifier
22305814
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.
Results Reference
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PubMed Identifier
33749310
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.
Results Reference
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PubMed Identifier
31524498
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.
Results Reference
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PubMed Identifier
28447181
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.
Results Reference
background
PubMed Identifier
34007324
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.
Results Reference
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Dapagliflozin Effect on Rheumatic Mitral Stenosis

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