Gliflozins on HF in Regurgitant Rheumatic Heart

Heart Failure Clinical Trial

Official title:

Effect of Gliflozins on Heart Failure Due to Regurgitant Rheumatic Valve Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06097585
• Other study ID #: gliflozins on rheumatic HF
• Status: Not yet recruiting
• Start date: December 1, 2023
• Est. completion date: April 1, 2025

Study information

• Verified date: October 2023
• Source: Assiut University
• Contact: Ahmed Y Dandrawy, Bachelor
• Phone: +201013086863
• Email: ahmed_youssef200[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of this trial is to detect impact of Gliflozin on patients with heart failure due to reurgitant rheumatic valve disease

Description:

• Rheumatic heart disease is a chronic sequel of acute rheumatic fever caused by group A β hemolytic Streptococcal pharyngitis and possibly pyoderma, which mimics molecular heart structures so the immune response leads to carditis and valvular heart damage. Damage to valves cause mitral and/or aortic regurgitation, or in long-standing stenosis. Complications of rheumatic heart disease include heart failure, embolic stroke, endocarditis and atrial fibrillation .

• Heart failure (HF) is a progressive syndrome characterised by the inability of the heart to provide adequate blood supply to meet the metabolic demand of different tissues .

• The recent ESC/AHA/ACC guidelines of HF set medications as class 1 for the HF therapy as ACE-I/ ARNI/beta-blocker/MRA/ SGLT2 I as they reduced the risk of cardiovascular death and worsening HF in patients with HFrEF , Unless contraindicated or not tolerated.

• Empagliflozin is an orally available inhibitor sodium glucose co-transporter 2 receptor (SGLT-2), empagliflozin exerts its effect by preventing sodium and glucose reabsorption from proximal convoluted tubules. This leads to increased urinary sodium and glucose excretion, This is associated with a modest osmotic diuresis, blood pressure lowering effect, improvement in arterial stiffness , and decrease in heart rate.

• DAPA-HF trial shows: The primary outcome of cardiovascular death, HF hospitalization, for dapagliflozin vs. placebo, was 16.3% vs 21.2% (p < 0.001).

• EMPA-REG OUTCOME trial shows: The primary outcome, cardiovascular death or HF hospitalization, for empagliflozin vs. placebo, was 19.4% vs. 24.7% ( p < 0.001).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: April 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All male or female patients having rheumatic heart disease with either mitral, aortic, tricuspid regurge as a single or combined valvular lesion

• Patients aged 18 years or older at time of inclusion in the study

• Patients with HF currently in NYHA class II-IV, or asymptomatic patients with proved mitral regurgitant lesion.

• Body Mass Index (BMI) < 45 kg/m2

Exclusion Criteria:

• Advanced stage liver and kidney failure (glomerular filtration rate < 20 mL/min/1.73 m2).

• Patient with implanted cardiac pacemaker, implantable cardioverter-defibrillator (ICD) or cardiac re-synchronization therapy (CRT) or implanted left ventricular assist device (LVAD)

• Diagnosis of cardiomyopathy induced by other etiologies rather than rheumatic heart disease eg, ischemia , dilated cardiomyopathy,…..etc within the 12 months prior to Visit 1

• Known allergy or hypersensitivity to SGLT-2 inhibitors

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial

• ongoing hematological diseases and malignancies

Related Conditions & MeSH terms

• Heart Diseases
• Heart Failure
• Rheumatic Diseases
• Rheumatic Heart Disease

Intervention

Drug:
• SGLT2 inhibitor
case control study in which group will receive SGLT2I and group will not , to detect impact of the drug in changing NYHA class for heart failure and echographic parameter

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (8)

Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, Nodari S, Lam CSP, Sato N, Shah AN, Gheorghiade M. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014 Apr 1;63(12):1123-1133. doi: 10.1016/j.jacc.2013.11.053. Epub 2014 Feb 5. — View Citation

Carapetis JR, Beaton A, Cunningham MW, Guilherme L, Karthikeyan G, Mayosi BM, Sable C, Steer A, Wilson N, Wyber R, Zuhlke L. Acute rheumatic fever and rheumatic heart disease. Nat Rev Dis Primers. 2016 Jan 14;2:15084. doi: 10.1038/nrdp.2015.84. — View Citation

Chilton R, Tikkanen I, Cannon CP, Crowe S, Woerle HJ, Broedl UC, Johansen OE. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015 Dec;17(12):1180-93. doi: 10.1111/dom.12572. Epub 2015 Oct 9. — View Citation

Fitchett D, Inzucchi SE, Cannon CP, McGuire DK, Scirica BM, Johansen OE, Sambevski S, Kaspers S, Pfarr E, George JT, Zinman B. Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Circulation. 2019 Mar 12;139(11):1384-1395. doi: 10.1161/CIRCULATIONAHA.118.037778. — View Citation

Inzucchi SE, Zinman B, Wanner C, Ferrari R, Fitchett D, Hantel S, Espadero RM, Woerle HJ, Broedl UC, Johansen OE. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015 Mar;12(2):90-100. doi: 10.1177/1479164114559852. Epub 2015 Jan 14. — View Citation

McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19. — View Citation

Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28. — View Citation

Zuhlke LJ, Beaton A, Engel ME, Hugo-Hamman CT, Karthikeyan G, Katzenellenbogen JM, Ntusi N, Ralph AP, Saxena A, Smeesters PR, Watkins D, Zilla P, Carapetis J. Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations. Curr Treat Options Cardiovasc Med. 2017 Feb;19(2):15. doi: 10.1007/s11936-017-0513-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of the clinical condition	improving or worsening in NYHA class: I- Ordinary physical activity does not cause undue fatigue, dyspnea, or palpitations.; II- Ordinary physical activity causes fatigue, dyspnea, palpitations, or angina.; III- Comfortable at rest; less than ordinary physical activity causes fatigue, dyspnea, palpitations, or angina.; IV- Symptoms occur at rest; any physical activity increases discomfort.	6 months up to 1 year
Primary	change of the function and regurge	improving or worsening in echocardiographic parameter : ejection fraction by simpson methods; severity of regurge by color Doppler and continuous wave Doppler	6 months up to 1 year
Secondary	major adverse cardiovascular event	monitor rate for Cardiovascular death, non-fatal stroke, non-fatal myocardial infarction and hospitalization for HF between 2 groups	6 months up to 1 year
Secondary	Glomerular filtration rate affection	monitor rate of decline in the estimated glomerular filtration rate between 2 groups	6 months up to 1 year
Secondary	urinary tract infection	incidence of urinary tract infection between 2 groups by following urine analysis	6 months up to 1 year